Sample records for taste aversion learning
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Rabin, B.M.; Hunt, W.A.; Lee, J.
1987-01-01
Three experiments were run to assess the role of the area postrema in taste-aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning to intact ratsmore » and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less-severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste-aversion learning may involve area post-remamediated mechanisms, particularly at the lower doses, but an intact area postrema is not a necessary condition of the acquisition of an amphetamine-induced taste aversion.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Rabin, B.M.; Hunt, W.A.; Lee, J.
1987-08-01
Three experiments were run to assess the role of the area postrema in taste aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning in intactmore » rats and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste aversion learning may involve area postrema-mediated mechanisms, particularly at the lower doses, but that an intact area postrema is not a necessary condition for the acquisition of an amphetamine-induced taste aversion.« less
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Preexposure to Salty and Sour Taste Enhances Conditioned Taste Aversion to Novel Sucrose
ERIC Educational Resources Information Center
Flores, Veronica L.; Moran, Anan; Bernstein, Max; Katz, Donald B.
2016-01-01
Conditioned taste aversion (CTA) is an intensively studied single-trial learning paradigm whereby animals are trained to avoid a taste that has been paired with malaise. Many factors influence the strength of aversion learning; prominently studied among these is taste novelty--the fact that preexposure to the taste conditioned stimulus (CS)…
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Role of the area postrema in radiation-induced taste aversion learning and emesis in cats
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rabin, B.M.; Hunt, W.A.; Chedester, A.L.
1986-01-01
The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved inmore » the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis.« less
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ERIC Educational Resources Information Center
Masaki, Takahisa; Nakajima, Sadahiko
2010-01-01
Swimming endows rats with an aversion to a taste solution consumed before swimming. The present study explored whether the experience of swimming before or after the taste-swimming trials interferes with swimming-based taste aversion learning. Experiment 1 demonstrated that a single preexposure to 20 min of swimming was as effective as four or…
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Further evidence for conditioned taste aversion induced by forced swimming.
Masaki, Takahisa; Nakajima, Sadahiko
2005-01-31
A series of experiments with rats reported that aversion to a taste solution can be established by forced swimming in a water pool. Experiment 1 demonstrated that correlation of taste and swimming is a critical factor for this phenomenon, indicating associative (i.e., Pavlovian) nature of this learning. Experiment 2 showed that this learning obeys the Pavlovian law of strength, by displaying a positive relationship between the duration of water immersion in training and the taste aversion observed in subsequent testing. Experiment 3 revealed that swimming rather than being wet is the critical agent, because a water shower did not endow rats with taste aversion. Experiment 4 found that taste aversion was a positive function of water level of the pools in training (0, 12 or 32 cm). These results, taken together, suggest that energy expenditure caused by physical exercise might be involved in the development of taste aversion.
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Cholinergic dependence of taste memory formation: evidence of two distinct processes.
Gutiérrez, Ranier; Rodriguez-Ortiz, Carlos J; De La Cruz, Vanesa; Núñez-Jaramillo, Luis; Bermudez-Rattoni, Federico
2003-11-01
Learning the aversive or positive consequences associated with novel taste solutions has a strong significance for an animal's survival. A lack of recognition of a taste's consequences could prevent ingestion of potential edibles or encounter death. We used conditioned taste aversion (CTA) and attenuation of neophobia (AN) to study aversive and safe taste memory formation. To determine if muscarinic receptors in the insular cortex participate differentially in both tasks, we infused the muscarinic antagonists scopolamine at distinct times before or after the presentation of a strong concentration of saccharin, followed by either an i.p. injection of a malaise-inducing agent or no injection. Our results showed that blockade of muscarinic receptors before taste presentation disrupts both learning tasks. However, the same treatment after the taste prevents AN but not CTA. These results clearly demonstrate that cortical cholinergic activity participates in the acquisition of both safe and aversive memory formation, and that cortical muscarinic receptors seem to be necessary for safe but not for aversive taste memory consolidation. These results suggest that the taste memory trace is processed in the insular cortex simultaneously by at least two independent mechanisms, and that their interaction would determine the degree of aversion or preference learned to a novel taste.
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Conditioned taste aversion, drugs of abuse and palatability
Lin, Jian-You; Arthurs, Joe; Reilly, Steve
2014-01-01
LIN, J.-Y., J. Arthurs and S. Reilly. Conditioned taste aversion: Palatability and drugs of abuse. NEUROSCI BIOBEHAV REV XX(x) XXX-XXX, 2014. – We consider conditioned taste aversion to involve a learned reduction in the palatability of a taste (and hence in amount consumed) based on the association that develops when a taste experience is followed by gastrointestinal malaise. The present article evaluates the well-established finding that drugs of abuse, at doses that are otherwise considered rewarding and self-administered, cause intake suppression. Our recent work using lick pattern analysis shows that drugs of abuse also cause a palatability downshift and, therefore, support conditioned taste aversion learning. PMID:24813806
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Rabin, B.M.; Hunt, W.A.; Lee, J.
1987-01-01
These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste-aversion learning. The first experiment determined the threshold for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride did produce a taste aversion when the two treatments were administered within 1 hr or each other. The resultsmore » are discussed in terms of the implications of these findings for understanding the nature of the unconditional stimuli leading to the acquisition of a conditioned taste aversion.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Rabin, B.M.; Hunt, W.A.; Lee, J.
1989-01-01
The pre-exposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride, and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired pre-exposures to lithium chloride blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiationmore » or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Rabin, B.M.; Hunt, W.A.; Lee, J.
1988-12-01
The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO)more » disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.« less
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Rabin, B M; Hunt, W A; Lee, J
1988-12-01
The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO) disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.
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Acquisition of lithium chloride- and radiation-induced taste aversions in hypophysectomized rats.
Rabin, B M; Hunt, W A; Lee, J
1983-03-01
The effects of hypophysectomy on the acquisition of conditioned taste aversions following injection of lithium chloride and following exposure to ionizing radiation were studied using a two-bottle preference test. Hypophysectomy did not disrupt the acquisition of a taste aversion following either treatment. The results are interpreted as: (a) suggesting that pituitary/adrenal hormones do not mediate the acquisition of a conditioned taste aversion following injections of lithium chloride or following exposure to ionizing radiation in a two-bottle preference test, and (b) consistent with other research suggesting that the involvement of pituitary/adrenal hormones in taste aversion learning may be related to the conflict induced by using a one-bottle test and not to the learning itself.
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Rabin, B M; Hunt, W A
1992-09-01
The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Rabin, B.M.; Hunt, W.A.; Lee, J.
1987-08-01
These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride didmore » produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.« less
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Rabin, B M; Hunt, W A; Lee, J
1987-08-01
These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride did produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.
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Does Conspecific Fighting Yield Conditioned Taste Aversion in Rats?
ERIC Educational Resources Information Center
Nakajima, Sadahiko; Kumazawa, Gaku; Ieki, Hayato; Hashimoto, Aya
2012-01-01
Running in an activity wheel yields conditioned aversion to a taste solution consumed before the running, but its underlying physiological mechanism is unknown. According to the claim that energy expenditure or general stress caused by physical exercise is a critical factor for this taste-aversion learning, not only running but also other…
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ERIC Educational Resources Information Center
Fontanini, Alfredo; Katz, Donald B.; Wang, Yunyan
2006-01-01
Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in…
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Rabin, B M; Hunt, W A
1983-04-01
A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning.
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A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice.
Eddy, Meghan C; Eschle, Benjamin K; Peterson, Darlene; Lauras, Nathan; Margolskee, Robert F; Delay, Eugene R
2012-06-01
Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances.
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Preexposure to salty and sour taste enhances conditioned taste aversion to novel sucrose
Flores, Veronica L.; Moran, Anan; Bernstein, Max
2016-01-01
Conditioned taste aversion (CTA) is an intensively studied single-trial learning paradigm whereby animals are trained to avoid a taste that has been paired with malaise. Many factors influence the strength of aversion learning; prominently studied among these is taste novelty—the fact that preexposure to the taste conditioned stimulus (CS) reduces its associability. The effect of exposure to tastes other than the CS has, in contrast, received little investigation. Here, we exposed rats to sodium chloride (N) and citric acid (C), either before or within a conditioning session involving novel sucrose (S). Presentation of this taste array within the conditioning session weakened the resultant S aversion, as expected. The opposite effect, however, was observed when exposure to the taste array was provided in sessions that preceded conditioning: such experience enhanced the eventual S aversion—a result that was robust to differences in CS delivery method and number of tastes presented in conditioning sessions. This “non-CS preexposure effect” scaled with the number of tastes in the exposure array (experience with more stimuli was more effective than experience with fewer) and with the amount of exposure sessions (three preexposure sessions were more effective than two). Together, our results provide evidence that exposure and experience with the realm of tastes changes an animal's future handling of even novel tastes. PMID:27084929
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ERIC Educational Resources Information Center
Bermudez-Rattoni, Federico; Ramirez-Lugo, Leticia; Zavala-Vega, Sergio
2006-01-01
Animals recognize a taste cue as aversive when it has been associated with post-ingestive malaise; this associative learning is known as conditioned taste aversion (CTA). When an animal consumes a new taste and no negative consequences follow, it becomes recognized as a safe signal, leading to an increase in its consumption in subsequent…
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Reyes-López, J; Nuñez-Jaramillo, L; Morán-Guel, E; Miranda, M I
2010-08-11
The medial prefrontal cortex (mPFC) is a brain area crucial for memory, attention, and decision making. Specifically, the noradrenergic system in this cortex is involved in aversive learning, as well as in the retrieval of these memories. Some evidence suggests that this area has an important role during taste memory, particularly during conditioned taste aversion (CTA), a model of aversive memory. Despite some previous evidence, there is scarce information about the role of adrenergic receptors in the mPFC during formation of aversive taste memory and appetitive/incidental taste memory. The goal of this research was to evaluate the role of mPFC beta-adrenergic receptors during CTA acquisition/consolidation or CTA retrieval, as well as during incidental taste memory formation using the model of latent inhibition of CTA. The results showed that infusions in the mPFC of the beta-adrenergic antagonist propranolol before CTA acquisition impaired both short- and long-term aversive taste memory formation, and also that propranolol infusions before the memory test impaired CTA retrieval. However, propranolol infusions before pre-exposure to the taste during the latent inhibition procedure had no effect on incidental taste memory acquisition or consolidation. These data indicate that beta-adrenergic receptors in the mPFC have different functions during taste memory formation: they have an important role during aversive taste association as well as during aversive retrieval but not during incidental taste memory formation. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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Taste-dependent sociophobia: when food and company do not mix.
Guitton, Matthieu J; Klin, Yael; Dudai, Yadin
2008-08-22
Using a combination of the paradigm of conditioned taste aversion (CTA) and of the paradigm of social interactions, we report here that in the rat, eating while anxious may result in long-term alterations in social behavior. In the conventional CTA, the subject learns to associate a tastant (the conditioned stimulus, CS) with delayed toxicosis (an unconditioned stimulus, UCS) to yield taste aversion (the conditioned response, CR). However, the association of taste with delayed negative internal states that could generate CRs that are different from taste aversion should not be neglected. Such associations may contribute to the ontogenesis, reinforcement and symptoms of some types of taste- and food-related disorders. We have recently reported that a delayed anxiety-like state, induced by the anxiogenic drug meta-chlorophenylpiperazine (mCPP), can specifically associate with taste to produce CTA. We now show that a similar protocol results in a marked lingering impairment in social interactions in response to the conditioned taste. This is hence a learned situation in which food and company do not mix well.
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Greenshaw, A J; Turrkish, S; Davis, B A
2002-01-01
The functional aversive stimulus properties of several IP doses of (+/-)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg-1) were measured with the conditioned taste aversion (CTA) paradigm. A two-bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (+/-)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (+/-)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (+/-)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (+/-)-amphetamine and PEA are self-administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives.
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ERIC Educational Resources Information Center
Gamiz, Fernando; Gallo, Milagros
2011-01-01
We have investigated the effect of protein kinase Mzeta (PKM[zeta]) inhibition in the basolateral amygdala (BLA) upon the retention of a nonspatial learned active avoidance response and conditioned taste-aversion (CTA) acquisition in rats. ZIP (10 nmol/[mu]L) injected into the BLA 24 h after training impaired retention of a learned…
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ERIC Educational Resources Information Center
Roitman, Mitchell F.; Wheeler, Robert A.; Tiesinga, Paul H. E.; Roitman, Jamie D.; Carelli, Regina M.
2010-01-01
The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli. Learning can alter the hedonic valence of a given stimulus, and it remains unclear how the NAc encodes this shift. The present study examined whether the population response of NAc neurons to a taste stimulus is plastic using a conditioned taste aversion (CTA)…
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ERIC Educational Resources Information Center
Bi, Ai-Ling; Wang, Yue; Li, Bo-Qin; Wang, Qian-Qian; Ma, Ling; Yu, Hui; Zhao, Ling; Chen, Zhe-Yu
2010-01-01
Actin rearrangement plays an essential role in learning and memory; however, the spatial and temporal regulation of actin dynamics in different phases of associative memory has not been fully understood. Here, using the conditioned taste aversion (CTA) paradigm, we investigated the region-specific involvement of actin rearrangement-related…
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ERIC Educational Resources Information Center
Miranda, Maria Isabel; Quirarte, Gina L.; Rodriguez-Garcia, Gabriela; McGaugh, James L.; Roozendaal, Benno
2008-01-01
It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function.…
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ABA, AAB and ABC Renewal in Taste Aversion Learning
ERIC Educational Resources Information Center
Bernal-Gamboa, Rodolfo; Juarez, Yectivani; Gonzalez-Martin, Gabriela; Carranza, Rodrigo; Sanchez-Carrasco, Livia; Nieto, Javier
2012-01-01
Context renewal is identified when the conditioned response (CR) elicited by an extinguished conditioned stimulus (CS) reappears as a result of changing the contextual cues during the test. Two experiments were designed for testing contextual renewal in a conditioned taste aversion preparation. Experiment 1 assessed ABA and AAB context renewal,…
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Taste Aversions Conditioned by the Aversiveness of Insulin and Formalin: Role of CS Specificity
ERIC Educational Resources Information Center
Domjan, Michael; Levy, Carolyn J.
1977-01-01
Experimenters in the past have reported that when insulin is used as the unconditioned stimulus (US), rats will learn an aversion to a sodium chloride but not a sucrose solution, whereas with formalin as the US, they will learn an aversion to a sucrose but not a saline solution. The present experiments failed to confirm these findings. (Editor)
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NASA Astrophysics Data System (ADS)
Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.
Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.
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Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L
2005-09-01
We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.
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Delay, Eugene R; Kondoh, Takashi
2015-02-01
The primary taste of dried bonito dashi is thought to be umami, elicited by inosine 5'-monphosphate (IMP) and L-amino acids. The present study compared the taste qualities of 25% dashi with 5 basic tastes and amino acids using conditioned taste aversion methods. Although wild-type C57BL/6J mice with compromised olfactory systems generalized an aversion of dashi to all 5 basic tastes, generalization was greater to sucrose (sweet), citric acid (sour), and quinine (bitter) than to NaCl (salty) or monosodium L-glutamate (umami) with amiloride. At neutral pH (6.5-6.9), the aversion generalized to l-histidine, L-alanine, L-proline, glycine, L-aspartic acid, L-serine, and monosodium L-glutamate, all mixed with IMP. Lowering pH of the test solutions to 5.7-5.8 (matching dashi) with HCl decreased generalization to some amino acids. However, adding lactic acid to test solutions with the same pH increased generalization to 5'-inosine monophosphate, L-leucine, L-phenylalanine, L-valine, L-arginine, and taurine but eliminated generalization to L-histidine. T1R1 knockout mice readily learned the aversion to dashi and generalized the aversion to sucrose, citric acid, and quinine but not to NaCl, glutamate, or any amino acid. These results suggest that dashi elicits a complex taste in mice that is more than umami, and deleting T1R1 receptor altered but did not eliminate their ability to taste dashi. In addition, lactic acid may alter or modulate taste transduction or cell-to-cell signaling. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Perirhinal Cortex Muscarinic Receptor Blockade Impairs Taste Recognition Memory Formation
ERIC Educational Resources Information Center
Gutierrez, Ranier; De la Cruz, Vanesa; Rodriguez-Ortiz, Carlos J.; Bermudez-Rattoni, Federico
2004-01-01
The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition…
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NASA Technical Reports Server (NTRS)
Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.
2003-01-01
Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.
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The Procerebrum Is Necessary for Odor-Aversion Learning in the Terrestrial Slug "Limax Valentianus"
ERIC Educational Resources Information Center
Kasai, Yoko; Watanabe, Satoshi; Kirino, Yutaka; Matsuo, Ryota
2006-01-01
The terrestrial slug "Limax" has a highly developed ability to associate the odor of some foods (e.g., carrot juice) with aversive stimuli such as the bitter taste of quinidine solution. The procerebrum (PC) is a part of the slug's brain thought to be involved in odor-aversion learning, but direct evidence is still lacking. Here, the authors…
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Conditioned taste aversions: From poisons to pain to drugs of abuse.
Lin, Jian-You; Arthurs, Joe; Reilly, Steve
2017-04-01
Learning what to eat and what not to eat is fundamental to our well-being, quality of life, and survival. In particular, the acquisition of conditioned taste aversions (CTAs) protects all animals (including humans) against ingesting foods that contain poisons or toxins. Counterintuitively, CTAs can also develop in situations in which we know with absolute certainty that the food did not cause the subsequent aversive systemic effect. Recent nonhuman animal research, analyzing palatability shifts, has indicated that a wider range of stimuli than has been traditionally acknowledged can induce CTAs. This article integrates these new findings with a reappraisal of some known characteristics of CTA and presents a novel conceptual analysis that is broader and more comprehensive than previous accounts of CTA learning.
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Conditioned taste aversions: From poisons to pain to drugs of abuse
Lin, Jian-You; Arthurs, Joe; Reilly, Steve
2018-01-01
Learning what to eat and what not to eat is fundamental to our well-being, quality of life and survival. In particular, the acquisition of conditioned taste aversions (CTAs) protects all animals (including humans) against ingesting foods that contain poisons or toxins. Counterintuitively, CTAs can also develop in situations where we know with absolute certainty that the food did not cause the subsequent aversive systemic effect. Recent non-human animal research, analyzing palatability shifts, indicates that a wider range of stimuli than traditionally acknowledged can induce CTAs. This article integrates these new findings with a reappraisal of some known characteristics of CTA, and presents a novel conceptual analysis that is broader and more comprehensive than other accounts of CTA learning. PMID:27301407
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ERIC Educational Resources Information Center
Merhav, Maayan; Rosenblum, Kobi
2008-01-01
Very little is known about the biological and molecular mechanisms that determine the effect of previous experience on implicit learning tasks. In the present study, we first defined weak and strong taste inputs according to measurements in the behavioral paradigm known as latent inhibition of conditioned taste aversion. We then demonstrated that…
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1990-06-30
gastronomes . In Food Aversion Learning, ed. N. W. Milgram, L. Krames, T. Alloway. New York: Plenum Press, 1977. Grill, H. J., Berridge, K. C. Taste...Jun 25 10:4,6:21 1990 ZLS: syr GRP: Po JOB: aug 0V: 12 Pb ok, &,vpr. VoL 4&, 000-=. 0 Pervnoe Press pl. 1990. Prited a tft USA . 0031-938"S90 53.00 + .00
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Schwager, Andrea L.; Sinclair, Michael S.; Tandon, Shashank; Taha, Sharif A.
2014-01-01
The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug. PMID:24695107
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Haack, Andrew K; Sheth, Chandni; Schwager, Andrea L; Sinclair, Michael S; Tandon, Shashank; Taha, Sharif A
2014-01-01
The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.
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What are the elements of motivation for acquisition of conditioned taste aversion?
Mita, Koichi; Okuta, Akiko; Okada, Ryuichi; Hatakeyama, Dai; Otsuka, Emi; Yamagishi, Miki; Morikawa, Mika; Naganuma, Yuki; Fujito, Yutaka; Dyakonova, Varvara; Lukowiak, Ken; Ito, Etsuro
2014-01-01
The pond snail Lymnaea stagnalis is capable of being classically conditioned to avoid food and to consolidate this aversion into a long-term memory (LTM). Previous studies have shown that the length of food deprivation is important for both the acquisition of taste aversion and its consolidation into LTM, which is referred to as conditioned taste aversion (CTA). Here we tested the hypothesis that the hemolymph glucose concentration is an important factor in the learning and memory of CTA. One-day food deprivation resulted in the best learning and memory, whereas more prolonged food deprivation had diminishing effects. Five-day food deprivation resulted in snails incapable of learning or remembering. During this food deprivation period, the hemolymph glucose concentration decreased. If snails were fed for 2days following the 5-day food deprivation, their glucose levels increased significantly and they exhibited both learning and memory, but neither learning nor memory was as good as with the 1-day food-deprived snails. Injection of the snails with insulin to reduce glucose levels resulted in better learning and memory. Insulin is also known to cause a long-term enhancement of synaptic transmission between the feeding-related neurons. On the other hand, injection of glucose into 5-day food-deprived snails did not alter their inability to learn and remember. However, if these snails were fed on sucrose for 3min, they then exhibited learning and memory formation. Our data suggest that hemolymph glucose concentration is an important factor in motivating acquisition of CTA in Lymnaea and that the action of insulin in the brain and the feeding behavior are also important factors. Copyright © 2013 Elsevier Inc. All rights reserved.
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Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A
2017-02-15
The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press-evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham- and LHb-lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol-induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
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Mechanisms of Radiation-Induced Conditioned Taste Aversion Learning
1986-01-01
to Walter A. Hunt. 86 4 21 144 . J Jr -.W U *’ = 7 . 7 .: M: W. ,WLW;i , .-, -’ .’P. %k T .- - ’ .: ’W ; .a --,.-" -. t .:-. , 56 RABIN AND HUNT can...8217. 7m. U RADIATION-INDUCED TASTE AVERSIONS 57 induced CTA 11021. Alternatively, when the antihistamine is [ 21 . A radiation-induced CTA can be...in rats. Pharmmad psychioactive drugs. J (omp Phvsiod Pvchld .;’: 21 -26. 1972. Biochem Behav 17: 305-311. 1982. 4. Berger. B. D.. C. D. Wise and L
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Odor-mediated taste learning requires dorsal hippocampus, but not basolateral amygdala activity
Wheeler, Daniel S.; Chang, Stephen E.; Holland, Peter C.
2013-01-01
Mediated learning is a unique cognitive phenomenon in which mental representations of physically absent stimuli enter into associations with directly-activated representations of physically present stimuli. Three experiments investigated the functional physiology of mediated learning involving the use of odor-taste associations. In Experiments 1a and 1b, basolateral amygdala lesions failed to attenuate mediated taste aversion learning. In Experiment 2, dorsal hippocampus inactivation impaired mediated learning, but left direct learning intact. Considered with past studies, the results implicate the dorsal hippocampus in mediated learning generally, and suggest a limit on the importance of the basolateral amygdala. PMID:23274135
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Sheth, Chandni; Furlong, Teri M; Keefe, Kristen A; Taha, Sharif A
2016-10-01
Ethanol has rewarding and aversive properties, and the balance of these properties influences voluntary ethanol consumption. Preclinical and clinical evidence show that the aversive properties of ethanol limit intake. The neural circuits underlying ethanol-induced aversion learning are not fully understood. We have previously shown that the lateral habenula (LHb), a region critical for aversive conditioning, plays an important role in ethanol-directed behaviors. However, the neurocircuitry through which LHb exerts its actions is unknown. In the present study, we investigate a role for the rostromedial tegmental nucleus (RMTg), a major LHb projection target, in regulating ethanol-directed behaviors. Rats received either sham or RMTg lesions and were studied during voluntary ethanol consumption; operant ethanol self-administration, extinction, and yohimbine-induced reinstatement of ethanol-seeking; and ethanol-induced conditioned taste aversion (CTA). RMTg lesions increased voluntary ethanol consumption and accelerated extinction of ethanol-induced CTA. The RMTg plays an important role in regulating voluntary ethanol consumption, possibly by mediating ethanol-induced aversive conditioning.
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Parabrachial gustatory lesions impair taste aversion learning in rats.
Spector, A C; Norgren, R; Grill, H J
1992-02-01
Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, intact rats (n = 15) and rats with PBN lesions (PBNX; n = 10) received seven intraoral taste stimulus infusions (30 s, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profile from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit.
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Optogenetic Induction of Aversive Taste Memory
C. Keene, Alex; Masek, Pavel
2013-01-01
The Drosophila melanogaster gustatory system consists of several neuronal pathways representing diverse taste modalities. The two predominant modalities are a sweet sensing pathway that mediates attraction, and a bitter sensing pathway that mediates avoidance. A central question is how flies integrate stimuli from these pathways and generate the appropriate behavioral response. We have developed a novel assay for induction of taste memories. We demonstrate that the gustatory response to fructose is suppressed when followed by the presence of bitter quinine. We employ optogenetic neural activation using infrared laser in combination with heat sensitive channel - TRPA1 to precisely activate gustatory neurons. This optogenetic system allows for spatially and temporally controlled activation of distinct neural classes in the gustatory circuit. We directly activated bitter-sensing neurons together with presentation of fructose for remote induction of aversive taste memories. Here we report that activation of bitter-sensing neurons in the proboscis suffices as a conditioning stimulus. Spatially restricted stimulation indicates that the conditioning stimulus is indeed a signal from the bitter neurons in the proboscis and it is independent of postingestive feedback. The coincidence of temporally specific activation of bitter-sensing neurons with fructose presentation is crucial for memory formation, establishing aversive taste learning in Drosophila as associative learning. Taken together, this optogenetic system provides a powerful new tool for interrogation of the central brain circuits that mediate memory formation. PMID:22820051
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Conditioned taste aversion and motion sickness in cats and squirrel monkeys
NASA Technical Reports Server (NTRS)
Fox, Robert A.; Corcoran, Meryl Lee; Brizzee, Kenneth R.
1991-01-01
The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.
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Learning context modulates aversive taste strength in honey bees.
de Brito Sanchez, Maria Gabriela; Serre, Marion; Avarguès-Weber, Aurore; Dyer, Adrian G; Giurfa, Martin
2015-03-01
The capacity of honey bees (Apis mellifera) to detect bitter substances is controversial because they ingest without reluctance different kinds of bitter solutions in the laboratory, whereas free-flying bees avoid them in visual discrimination tasks. Here, we asked whether the gustatory perception of bees changes with the behavioral context so that tastes that are less effective as negative reinforcements in a given context become more effective in a different context. We trained bees to discriminate an odorant paired with 1 mol l(-1) sucrose solution from another odorant paired with either distilled water, 3 mol l(-1) NaCl or 60 mmol l(-1) quinine. Training was either Pavlovian [olfactory conditioning of the proboscis extension reflex (PER) in harnessed bees], or mainly operant (olfactory conditioning of free-walking bees in a Y-maze). PER-trained and maze-trained bees were subsequently tested both in their original context and in the alternative context. Whereas PER-trained bees transferred their choice to the Y-maze situation, Y-maze-trained bees did not respond with a PER to odors when subsequently harnessed. In both conditioning protocols, NaCl and distilled water were the strongest and the weakest aversive reinforcement, respectively. A significant variation was found for quinine, which had an intermediate aversive effect in PER conditioning but a more powerful effect in the Y-maze, similar to that of NaCl. These results thus show that the aversive strength of quinine varies with the learning context, and reveal the plasticity of the bee's gustatory system. We discuss the experimental constraints of both learning contexts and focus on stress as a key modulator of taste in the honey bee. Further explorations of bee taste are proposed to understand the physiology of taste modulation in bees. © 2015. Published by The Company of Biologists Ltd.
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ERIC Educational Resources Information Center
Pineno, Oskar
2010-01-01
Two experiments were conducted to study overshadowing of extinction in a conditioned taste aversion preparation. In both experiments, aversive conditioning with sucrose was followed by extinction treatment with either sucrose alone or in compound with another taste, citric acid. Experiment 1 employed a simultaneous compound extinction treatment…
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Situational relevance: Context as a factor in serial overshadowing of taste aversion learning.
Kwok, Dorothy W S; Boakes, Robert A
2017-08-31
In a serial overshadowing procedure a target stimulus, A, is followed after an interval by a potentially interfering stimulus, B, and this is then followed by an unconditioned stimulus, US. Revusky (1977) proposed that the degree to which B overshadows conditioning of A depends on whether or not the two events take place in the same context. To test this proposal two experiments used a 1-trial long-delay conditioned taste aversion (CTA) procedure; sucrose served as the target taste (A) and dilute hydrochloric acid (HCl) as the overshadowing taste (B), with lithium chloride injection providing the US. In Experiment 1 these tastes were novel; weaker overshadowing by HCl of an aversion to sucrose was found when the two tastes were presented in different contexts. Experiment 2 tested whether the effect of pre-exposure to HCl, thereby rendering it less effective in overshadowing a sucrose aversion, was also context-dependent. In the conditioning session rats again received either context-same or context-different presentations of sucrose and HCl. However, for some rats HCl was pre-exposed in the same context to which it was later presented during conditioning (Consistent), while others were pre-exposed to HCl in a different context to the one in which it was presented during conditioning (Inconsistent). The Inconsistent group produced greater overshadowing than the Consistent group and thus confirmed that the latent inhibition effect was also context dependent. This study supports Revusky's (1977) idea of situational relevance.
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Effects of treadmill exercise on the LiCl-induced conditioned taste aversion in rats.
Tsuboi, Hisanori; Hirai, Yoshiyuki; Maezawa, Hitoshi; Notani, Kenji; Inoue, Nobuo; Funahashi, Makoto
2015-01-01
Studies have shown that exercise can enhance learning and memory. Conditioned taste aversion (CTA) is an avoidance behavior induced by associative memory of the taste sensation for something pleasant or neutral with a negative visceral reaction caused by the coincident action of a toxic substance that is tasteless or administered systemically. We sought to measure the effects of treadmill exercise on CTA in rats by investigating the effects of exercise on acquisition, extinction and spontaneous recovery of CTA. We made two groups of rats: an exercise group that ran on a treadmill, and a control group that did not have structured exercise periods. To condition rats to disfavor a sweet taste, consumption of a 0.1% saccharin solution in place of drinking water was paired with 0.15M LiCl (2% body weight, i.p.) to induce visceral discomfort. We measured changes of saccharin consumption during acquisition and extinction of CTA. The exercise and no-exercise groups both acquired CTA to similar levels and showed maximum extinction of CTA around 6 days after acquisition. This result indicates that exercise affects neither acquisition nor extinction of CTA. However, in testing for preservation of CTA after much longer extinction periods that included exercise or not during the intervening period, exercising animals showed a significantly lower saccharin intake, irrespective of having exercised or not during the conditioning phase of the trial. This result suggests that exercise may help to preserve aversive memory (taste aversion in this example) as evidence by the significant spontaneous recovery of aversion in exercising animals. Copyright © 2014 Elsevier Inc. All rights reserved.
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Keefe, Kristen A.; Taha, Sharif A.
2016-01-01
Key points The lateral habenula (LHb) has been implicated in regulation of drug‐seeking behaviours through aversion‐mediated learning.In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol‐induced conditioned taste aversion (CTA) to saccharin.Ethanol‐induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste.In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol‐induced CTA.Our results strongly suggest that excitation of LHb neurons is required for ethanol‐induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Abstract Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion‐mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol‐induced aversion, we recorded neural firing in the LHb of freely behaving, water‐deprived rats before and after an ethanol‐induced (1.5 g kg−1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol‐induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press‐evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham‐ and LHb‐lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol‐induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake. PMID:27682823
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Choice Behavior Guided by Learned, But Not Innate, Taste Aversion Recruits the Orbitofrontal Cortex.
Ramírez-Lugo, Leticia; Peñas-Rincón, Ana; Ángeles-Durán, Sandybel; Sotres-Bayon, Francisco
2016-10-12
The ability to select an appropriate behavioral response guided by previous emotional experiences is critical for survival. Although much is known about brain mechanisms underlying emotional associations, little is known about how these associations guide behavior when several choices are available. To address this, we performed local pharmacological inactivations of several cortical regions before retrieval of an aversive memory in choice-based versus no-choice-based conditioned taste aversion (CTA) tasks in rats. Interestingly, we found that inactivation of the orbitofrontal cortex (OFC), but not the dorsal or ventral medial prefrontal cortices, blocked retrieval of choice CTA. However, OFC inactivation left retrieval of no-choice CTA intact, suggesting its role in guiding choice, but not in retrieval of CTA memory. Consistently, OFC activity increased in the choice condition compared with no-choice, as measured with c-Fos immunolabeling. Notably, OFC inactivation did not affect choice behavior when it was guided by innate taste aversion. Consistent with an anterior insular cortex (AIC) involvement in storing taste memories, we found that AIC inactivation impaired retrieval of both choice and no-choice CTA. Therefore, this study provides evidence for OFC's role in guiding choice behavior and shows that this is dissociable from AIC-dependent taste aversion memory. Together, our results suggest that OFC is required and recruited to guide choice selection between options of taste associations relayed from AIC. Survival and mental health depend on being able to choose stimuli not associated with danger. This is particularly important when danger is associated with stimuli that we ingest. Although much is known about the brain mechanisms that underlie associations with dangerous taste stimuli, very little is known about how these stored emotional associations guide behavior when it involves choice. By combining pharmacological and immunohistochemistry tools with taste-guided tasks, our study provides evidence for the key role of orbitofrontal cortex activity in choice behavior and shows that this is dissociable from the adjacent insular cortex-dependent taste aversion memory. Understanding the brain mechanisms that underlie the impact that emotional associations have on survival choice behaviors may lead to better treatments for mental disorders characterized by emotional decision-making deficits. Copyright © 2016 the authors 0270-6474/16/3610574-10$15.00/0.
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Effects of pramipexole on the processing of rewarding and aversive taste stimuli.
McCabe, Ciara; Harwood, James; Brouwer, Sietske; Harmer, Catherine J; Cowen, Philip J
2013-07-01
Pramipexole, a D2/D3 dopamine receptor agonist, has been implicated in the development of impulse control disorders in patients with Parkinson's disease. Investigation of single doses of pramipexole in healthy participants in reward-based learning tasks has shown inhibition of the neural processing of reward, presumptively through stimulation of dopamine autoreceptors. This study aims to examine the effects of pramipexole on the neural response to the passive receipt of rewarding and aversive sight and taste stimuli. We used functional magnetic resonance imaging to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 16 healthy volunteers who received a single dose of pramipexole (0.25 mg) and placebo in a double-blind, within-subject, design. Relative to placebo, pramipexole treatment reduced blood oxygen level-dependent activation to the chocolate stimuli in the areas known to play a key role in reward, including the ventromedial prefrontal cortex, the orbitofrontal cortex, striatum, thalamus and dorsal anterior cingulate cortex. Pramipexole also reduced activation to the aversive condition in the dorsal anterior cingulate cortex. There were no effects of pramipexole on the subjective ratings of the stimuli. Our results are consistent with an ability of acute, low-dose pramipexole to diminish dopamine-mediated responses to both rewarding and aversive taste stimuli, perhaps through an inhibitory action of D2/3 autoreceptors on phasic burst activity of midbrain dopamine neurones. The ability of pramipexole to inhibit aversive processing might potentiate its adverse behavioural effects and could also play a role in its proposed efficacy in treatment-resistant depression.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Spector, A.C.; Smith, J.C.; Hollander, G.R.
1986-05-01
Radiation-induced taste aversion has been suggested to possibly play a role in the dietary difficulties observed in some radiotherapy patients. In rats, these aversions can still be formed even when the radiation exposure precedes the taste experience by several hours. This study was conducted to examine whether increasing the radiation exposure level could extend the range of the exposure-taste interval that would still support the formation of a taste aversion. Separate groups of rats received either a 100 or 300 R gamma-ray exposure followed 1, 3, 6, or 24 h later by a 10-min saccharin (0.1% w/v) presentation. A controlmore » group received a sham exposure followed 1 h later by a 10-min saccharin presentation. Twenty-four hours following the saccharin presentation all rats received a series of twelve 23-h two-bottle preference tests between saccharin and water. The results indicated that the duration of the exposure-taste interval plays an increasingly more important role in determining the initial extent of the aversion as the dose decreases. The course of recovery from taste aversion seems more affected by dose than by the temporal parameters of the conditioning trial.« less
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Jacobs, W J; Zellner, D A; LoLordo, V M; Riley, A L
1981-06-01
In the following experiment, multiple injections of morphine sulfate following the acquisition of a morphine-induced taste aversion had no effect on the retention of the previously acquired aversion. Post-conditioning injections of morphine resulted in the development of physical dependence to morphine and led to a decrement in the ability of morphine to induce a subsequent aversion to a second novel taste. This failure of post-conditioning exposures to morphine to affect a previously acquired morphine-induced taste aversion even though tolerance to morphine had occurred was discussed in the context of Rescorla's event-memory model of conditioning.
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Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats
Fowler, S.W.; Ramsey, A.K.; Walker, J.M.; Serfozo, P.; Olive, M.F.; Schachtman, T.R.; Simonyi, A.
2010-01-01
Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of learning processes and is important for inhibitory avoidance and conditioned taste aversion learning. MGlu5 receptors are physically connected with NMDA receptors and they interact with, and modulate, the function of one another in several brain regions. The present studies used systemic co-administration of an mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK-801) to characterize the interactions of these receptors in two aversive learning tasks. Male Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10 mg/kg, s.c.), delivered by itself prior to the conditioning trial, did not have any effect on performance in either task 48 hours after training. However, CDPPB (at 3 mg/kg) attenuated the MK-801 (0.2 mg/kg, i.p.) induced learning deficit in both tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie the importance of mGlu5 and NMDA receptor interactions in modulating memory processing, and are consistent with findings showing the efficacy of positive allosteric modulators of mGlu5 receptors in reversing the negative effects of NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor gating, or working, spatial and recognition memory. PMID:21093598
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Age-dependent MDPV-induced taste aversions and thermoregulation in adolescent and adult rats.
Merluzzi, Andrew P; Hurwitz, Zachary E; Briscione, Maria A; Cobuzzi, Jennifer L; Wetzell, Bradley; Rice, Kenner C; Riley, Anthony L
2014-07-01
Adolescent rats are more sensitive to the rewarding and less sensitive to the aversive properties of various drugs of abuse than their adult counterparts. Given a nationwide increase in use of "bath salts," the present experiment employed the conditioned taste aversion procedure to assess the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV; 0, 1.0, 1.8, or 3.2 mg/kg), a common constituent in "bath salts," in adult and adolescent rats. As similar drugs induce thermoregulatory changes in rats, temperature was recorded following MDPV administration to assess if thermoregulatory changes were related to taste aversion conditioning. Both age groups acquired taste aversions, although these aversions were weaker and developed at a slower rate in the adolescent subjects. Adolescents increased and adults decreased body temperature following MDPV administration with no correlation to aversions. The relative insensitivity of adolescents to the aversive effects of MDPV suggests that MDPV may confer an increased risk in this population. © 2013 Wiley Periodicals, Inc.
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ERIC Educational Resources Information Center
Kerfoot, Erin C.; Agarwal, Isha; Lee, Hongjoo J.; Holland, Peter C.
2007-01-01
Through associative learning, cues for biologically significant reinforcers such as food may gain access to mental representations of those reinforcers. Here, we used devaluation procedures, behavioral assessment of hedonic taste-reactivity responses, and measurement of immediate-early gene (IEG) expression to show that a cue for food engages…
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Effects of Swim Stress on Neophobia and Reconditioning Using a Conditioned Taste Aversion Procedure
ERIC Educational Resources Information Center
Walker, Jennifer M.; Ramsey, Ashley K.; Fowler, Stephanie W.; Schachtman, Todd R.
2012-01-01
Previous research has found that swim stress during a classical conditioning trial attenuates conditioned taste aversion (CTA). In the current study, rats were used to examine the effects of inescapable swim stress on the habituation of neophobia to a flavored solution and reacquisition of an extinguished conditioned taste aversion. In Experiment…
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Enhanced Extinction of Aversive Memories by High-Frequency Stimulation of the Rat Infralimbic Cortex
Maroun, Mouna; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara; Motanis, Helen
2012-01-01
Electrical stimulation of the rodent medial prefrontal cortex (mPFC), including the infralimbic cortex (IL), immediately prior to or during fear extinction training facilitates extinction memory. Here we examined the effects of high-frequency stimulation (HFS) of the rat IL either prior to conditioning or following retrieval of the conditioned memory, on extinction of Pavlovian fear and conditioned taste aversion (CTA). IL-HFS applied immediately after fear memory retrieval, but not three hours after retrieval or prior to conditioning, subsequently reduced freezing during fear extinction. Similarly, IL-HFS given immediately, but not three hours after, retrieval of a CTA memory reduced aversion during extinction. These data indicate that HFS of the IL may be an effective method for reducing both learned fear and learned aversion. PMID:22586453
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Nicotine-induced conditioned taste aversion in the rat: effects of ethanol.
Korkosz, Agnieszka; Scinska, Anna; Taracha, Ewa; Plaznik, Adam; Kukwa, Andrzej; Kostowski, Wojciech; Bienkowski, Przemyslaw
2006-05-10
It has been shown that small doses of ethanol antagonise the discriminative stimulus properties of nicotine in the rat. The aim of the present study was to evaluate whether ethanol could antagonise the aversive stimulus effects of nicotine. Wistar rats were trained to associate nicotine injections with a novel tasting fluid (0.1% saccharin) in the conditioned taste aversion procedure. Nicotine (0.3 mg/kg, s.c.) was injected 5 min after the end of a 20-min exposure to the saccharin solution. Ethanol (0.25-0.5 g/kg, i.p.) was administered 5 or 50 min before nicotine. In general, ethanol did not inhibit nicotine-induced conditioned taste aversion. Contrary to the findings in drug discrimination studies, a slight but significant enhancement of nicotine-induced taste aversion conditioning was observed after ethanol pre-treatment. Blood ethanol levels were measured in a separate group of rats. Maximal blood ethanol levels after i.p. administration of 0.25 or 0.5 g/kg ethanol exceeded 20 and 80 mg%, respectively. Concluding, the present results may indicate that ethanol does not attenuate nicotine-induced conditioned taste aversion in the rat.
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Genetic differences in ethanol-induced hyperglycemia and conditioned taste aversion
DOE Office of Scientific and Technical Information (OSTI.GOV)
Risinger, F.O.; Cunningham, C.L.
1992-01-01
Genetic differences in the hyperglycemic response to acute ethanol exposure and ethanol-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J and DBA/2J mice were injected with ethanol and blood glucose levels determined over 4 h. C57 mice demonstrated greater dose-dependent elevations in blood glucose compared to DBA mice. In a conditioned taste aversion procedure, water deprived mice received ethanol injections immediately after access to a NaCl flavored solution. DBA mice developed aversion to the ethanol-paired flavor at a lower dose than C57 mice. These results provide further support for a possible inverse genetic relationship between sensitivity tomore » ethanol-induced hyperglycemia and sensitivity to conditioned taste aversion.« less
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Ward-Fear, Georgia; Thomas, Jai; Webb, Jonathan K; Pearson, David J; Shine, Richard
2017-03-01
Conditioned taste aversion (CTA) is an adaptive learning mechanism whereby a consumer associates the taste of a certain food with symptoms caused by a toxic substance, and thereafter avoids eating that type of food. Recently, wildlife researchers have employed CTA to discourage native fauna from ingesting toxic cane toads (Rhinella marina), a species that is invading tropical Australia. In this paper, we compare the results of 2 sets of CTA trials on large varanid lizards ("goannas," Varanus panoptes). One set of trials (described in this paper) exposed recently-captured lizards to sausages made from cane toad flesh, laced with a nausea-inducing chemical (lithium chloride) to reinforce the aversion response. The other trials (in a recently-published paper, reviewed herein) exposed free-ranging lizards to live juvenile cane toads. The effectiveness of the training was judged by how long a lizard survived in the wild before it was killed (fatally poisoned) by a cane toad. Both stimuli elicited rapid aversion to live toads, but the CTA response did not enhance survival rates of the sausage-trained goannas after they were released into the wild. In contrast, the goannas exposed to live juvenile toads exhibited higher long-term survival rates than did untrained conspecifics. Our results suggest that although it is relatively easy to elicit short-term aversion to toad cues in goannas, a biologically realistic stimulus (live toads, encountered by free-ranging predators) is most effective at buffering these reptiles from the impact of invasive toxic prey. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.
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Conditioned taste aversion dependent regulation of amygdala gene expression.
Panguluri, Siva K; Kuwabara, Nobuyuki; Kang, Yi; Cooper, Nigel; Lundy, Robert F
2012-02-28
The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified "behavior" as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning. Copyright © 2011 Elsevier Inc. All rights reserved.
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Memory-updating abrogates extinction of learned immunosuppression.
Hadamitzky, Martin; Bösche, Katharina; Wirth, Timo; Buck, Benjamin; Beetz, Oliver; Christians, Uwe; Schniedewind, Björn; Lückemann, Laura; Güntürkün, Onur; Engler, Harald; Schedlowski, Manfred
2016-02-01
When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation. It is unknown, however, whether reconsolidation is restricted to neurocognitive processes such as fear memories or can be extended to peripheral physiological functions as well. Here, we show in a paradigm of behaviorally conditioned taste aversion in rats memory-updating in learned immunosuppression. The administration of sub-therapeutic doses of the immunosuppressant cyclosporin A together with the conditioned stimulus (CS/saccharin) during retrieval blocked extinction of conditioned taste aversion and learned suppression of T cell cytokine (interleukin-2; interferon-γ) production. This conditioned immunosuppression is of clinical relevance since it significantly prolonged the survival time of heterotopically transplanted heart allografts in rats. Collectively, these findings demonstrate that memories can be updated on both neural and behavioral levels as well as on the level of peripheral physiological systems such as immune functioning. Copyright © 2015 Elsevier Inc. All rights reserved.
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Effects of dietary choline availability on latent inhibition of flavor aversion learning.
Gámiz, Fernando; Recio, Sergio Andrés; Iliescu, Adela Florentina; Gallo, Milagros; de Brugada, Isabel
2015-08-01
It has been previously reported that dietary choline supplementation might affect latent inhibition (LI) using a conditioned suppression procedure in rats. We have assessed the effect of dietary choline on LI of flavor aversion learning. Adult male Wistar rats received a choline supplemented (5 g/kg), deficient (0 g/kg), or standard (1.1 g/kg) diet for 3 months. After this supplementation period, all rats went through a conditioned taste aversion (CTA) procedure, half of them being pre-exposed to the conditioned stimulus before the conditioning. The results indicated that choline deficiency prevents LI of conditioned flavor aversion to cider vinegar (3%) induced by a LiCl (0.15 M; 2% body weight) intraperitoneal injection, while choline supplementation enhances CTA leading to slower extinction. The role of the brain systems modulating attentional processes is discussed.
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Miranda, María Isabel; Rangel-Hernández, José Alejandro; Vera-Rivera, Gabriela; García-Medina, Nadia Edith; Soto-Alonso, Gerardo; Rodríguez-García, Gabriela; Núñez-Jaramillo, Luis
2017-09-17
The nucleus accumbens (NAcc) is a forebrain region that may significantly contribute to the integration of taste and visceral signals during food consumption. Changes in dopamine release in the NAcc have been observed during consumption of a sweet taste and during compulsive consumption of dietary sugars, suggesting that NAcc dopaminergic transmission is strongly correlated with taste familiarity and the hedonic value content. NAcc core and shell nuclei are differentially involved during and after sugar exposure and, particularly, previous evidence suggests that dopamine D2 receptors could be related with the strength of the latent inhibition (LI) of conditioned taste aversion (CTA), which depends on the length of the taste stimulus pre-exposure. Thus, the objective of this work was to evaluate, after long-term exposure to sugar, the function of dopaminergic D2 receptors in the NAcc core during taste memory retrieval preference test, and during CTA. Adult rats were exposed during 14days to 10% sugar solution as a single liquid ad libitum. NAcc core bilateral injections of D2 dopamine receptor antagonist, haloperidol (1μg/μL), were made before third preference test and CTA acquisition. We found that sugar was similarly preferred after 3 acute presentations or 14days of continued sugar consumption and that haloperidol did not disrupt this appetitive memory retrieval. Nevertheless, D2 receptors antagonism differentially affects aversive memory formation after acute or long-term sugar consumption. These results demonstrate that NAcc dopamine D2 receptors have a differential function during CTA depending on the degree of sugar familiarity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
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McCabe, Ciara; Rocha-Rego, Vanessa
2016-01-01
Dysfunctional neural responses to appetitive and aversive stimuli have been investigated as possible biomarkers for psychiatric disorders. However it is not clear to what degree these are separate processes across the brain or in fact overlapping systems. To help clarify this issue we used Gaussian process classifier (GPC) analysis to examine appetitive and aversive processing in the brain. 25 healthy controls underwent functional MRI whilst seeing pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to discriminate between the appetitive and aversive sights and tastes using functional activity patterns. The diagnostic accuracy of the GPC for the accuracy to discriminate appetitive taste from neutral condition was 86.5% (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced neutral taste stimuli the probability of correct classification was 92. The accuracy to discriminate aversive from neutral taste stimuli was 82.5% (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the sight modality, the accuracy to discriminate appetitive from neutral condition was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity = 92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was 63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). Our results demonstrate the predictive value of neurofunctional data in discriminating emotional and neutral networks of activity in the healthy human brain. It would be of interest to use pattern recognition techniques and fMRI to examine network dysfunction in the processing of appetitive, aversive and neutral stimuli in psychiatric disorders. Especially where problems with reward and punishment processing have been implicated in the pathophysiology of the disorder.
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ERIC Educational Resources Information Center
Miranda, Maria I.; McGaugh, James L.
2004-01-01
There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the…
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Sweet and bitter taste of ethanol in C57BL/6J and DBA2/J mouse strains.
Blizard, David A
2007-01-01
Studies of inbred strains of rats and mice have suggested a positive association between strain variations in sweet taste and ethanol intake. However, strain associations by themselves are insufficient to support a functional link between taste and ethanol intake. We used conditioned taste aversion (CTA) to explore the sweet and bitter taste of ethanol and ability to detect sucrose, quinine and ethanol in C57BL/6J (B6) and DBA/2J (D2) mouse strains that are frequently used in alcohol research. The present study showed that C57BL/6J mice generalized taste aversions from sucrose and quinine solutions to 10% ethanol and, reciprocally, aversions to 10% ethanol generalized to each of these solutions presented separately. Only conditioned aversions to quinine generalized to ethanol in the DBA/2J strain but an aversion conditioned to ethanol did not generalize reciprocally to quinine. Thus, considering these two gustatory qualities, 10% ethanol tastes both sweet and bitter to B6 mice but only bitter to D2. Both strains were able to generalize taste aversions across different concentrations of the same compound. B6 were able to detect lower concentrations of quinine than D2 but both strains were able to detect sucrose and (in contrast to previous findings) ethanol at similar concentrations. The strain-dependent gustatory profiles for ethanol may make an important contribution to the understanding of the undoubtedly complex mechanisms influencing high ethanol preference of B6 and pronounced ethanol avoidance of D2 mice.
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ERIC Educational Resources Information Center
Mickley, G. Andrew; DiSorbo, Anthony; Wilson, Gina N.; Huffman, Jennifer; Bacik, Stephanie; Hoxha, Zana; Biada, Jaclyn M.; Kim, Ye-Hyun
2009-01-01
Conditioned taste aversions (CTAs) may be acquired when an animal consumes a novel taste (CS) and then experiences the symptoms of poisoning (US). This aversion may be extinguished by repeated exposure to the CS alone. However, following a latency period in which the CS is not presented, the CTA will spontaneously recover (SR). In the current…
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Recognition by Rats of Binary Taste Solutions and Their Components.
Katagawa, Yoshihisa; Yasuo, Toshiaki; Suwabe, Takeshi; Yamamura, Tomoki; Gen, Keika; Sako, Noritaka
2016-09-13
This behavioral study investigated how rats conditioned to binary mixtures of preferred and aversive taste stimuli, respectively, responded to the individual components in a conditioned taste aversion (CTA) paradigm. The preference of stimuli was determined based on the initial results of 2 bottle preference test. The preferred stimuli included 5mM sodium saccharin (Sacc), 0.03M NaCl (Na), 0.1M Na, 5mM Sacc + 0.03M Na, and 5mM Sacc + 0.2mM quinine hydrochloride (Q), whereas the aversive stimuli tested were 1.0M Na, 0.2mM Q, 0.3mM Q, 5mM Sacc + 1.0M Na, and 5mM Sacc + 0.3mM Q. In CTA tests where LiCl was the unconditioned stimulus, the number of licks to the preferred binary mixtures and to all tested preferred components were significantly less than in control rats. No significant difference resulted between the number of licks to the aversive binary mixtures or to all tested aversive components. However, when rats pre-exposed to the aversive components contained of the aversive binary mixtures were conditioned to these mixtures, the number of licks to all the tested stimuli was significantly less than in controls. Rats conditioned to components of the aversive binary mixtures generalized to the binary mixtures containing those components. These results suggest that rats recognize and remember preferred and aversive taste mixtures as well as the preferred and aversive components of the binary mixtures, and that pre-exposure before CTA is an available method to study the recognition of aversive taste stimuli. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Miranda, María I.; McGaugh, James L.
2004-01-01
There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the acquisition/consolidation of conditioned taste aversion (CTA). Posttraining infusion into the IC of 0.3 μg oxotremorine and 1.25 μg 8-Br-cAMP enhanced IA retention. Infusions of 8-Br-cAMP, but not oxotremorine, into the IC enhanced taste aversion. The experiments also examined whether noradrenergic activity in the basolateral amygdala (BLA) is critical in enabling the enhancement of CTA and IA memory induced by drug infusions administered into the IC. For both CTA and IA, ipsilateral infusions of β-adrenergic antagonist propranolol administered into the BLA blocked the retention-enhancing effect of 8-Br-cAMP or oxotremorine infused into the IC. These results indicate that the IC is involved in the consolidation of memory for both IA and CTA, and this effect requires intact noradrenergic activity into the BLA. These findings provide additional evidence that the BLA interacts with other brain regions, including sensory cortex, in modulating memory consolidation. PMID:15169861
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Yiannakas, Adonis; Rosenblum, Kobi
2017-01-01
The sense of taste is a key component of the sensory machinery, enabling the evaluation of both the safety as well as forming associations regarding the nutritional value of ingestible substances. Indicative of the salience of the modality, taste conditioning can be achieved in rodents upon a single pairing of a tastant with a chemical stimulus inducing malaise. This robust associative learning paradigm has been heavily linked with activity within the insular cortex (IC), among other regions, such as the amygdala and medial prefrontal cortex. A number of studies have demonstrated taste memory formation to be dependent on protein synthesis at the IC and to correlate with the induction of signaling cascades involved in synaptic plasticity. Taste learning has been shown to require the differential involvement of dopaminergic GABAergic, glutamatergic, muscarinic neurotransmission across an extended taste learning circuit. The subsequent activation of downstream protein kinases (ERK, CaMKII), transcription factors (CREB, Elk-1) and immediate early genes (c-fos, Arc), has been implicated in the regulation of the different phases of taste learning. This review discusses the relevant neurotransmission, molecular signaling pathways and genetic markers involved in novel and aversive taste learning, with a particular focus on the IC. Imaging and other studies in humans have implicated the IC in the pathophysiology of a number of cognitive disorders. We conclude that the IC participates in circuit-wide computations that modulate the interception and encoding of sensory information, as well as the formation of subjective internal representations that control the expression of motivated behaviors. PMID:29163022
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Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.
Jones, Jermaine D; Busse, Gregory D; Riley, Anthony L
2006-04-01
Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.
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1992-01-01
SR2-1 Cisplatin-induced conditioned taste aversion: ateuto by dexamethasone but not zacopride or GR38032F Nm I- Paul C Mele, John R. McDonough, David...to 5-H1’, receptor blockade. 5-HT., receptor antagonists; Zacopridc: GR38032F; Desamethasone: Cisplatin: Taste aversion (conditioned) I. Introductlon...intake) was used as the area known as the chemoreceptor trigger zone (Borri- index of the CTA. son, 1974). Moreover. the findings that rats, ferrets
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Medial prefrontal cortex dopamine controls the persistent storage of aversive memories
Gonzalez, María C.; Kramar, Cecilia P.; Tomaiuolo, Micol; Katche, Cynthia; Weisstaub, Noelia; Cammarota, Martín; Medina, Jorge H.
2014-01-01
Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus. PMID:25506318
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McCabe, Ciara; Rocha-Rego, Vanessa
2016-01-01
Background Dysfunctional neural responses to appetitive and aversive stimuli have been investigated as possible biomarkers for psychiatric disorders. However it is not clear to what degree these are separate processes across the brain or in fact overlapping systems. To help clarify this issue we used Gaussian process classifier (GPC) analysis to examine appetitive and aversive processing in the brain. Method 25 healthy controls underwent functional MRI whilst seeing pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to discriminate between the appetitive and aversive sights and tastes using functional activity patterns. Results The diagnostic accuracy of the GPC for the accuracy to discriminate appetitive taste from neutral condition was 86.5% (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced neutral taste stimuli the probability of correct classification was 92. The accuracy to discriminate aversive from neutral taste stimuli was 82.5% (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the sight modality, the accuracy to discriminate appetitive from neutral condition was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity = 92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was 63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). Conclusions Our results demonstrate the predictive value of neurofunctional data in discriminating emotional and neutral networks of activity in the healthy human brain. It would be of interest to use pattern recognition techniques and fMRI to examine network dysfunction in the processing of appetitive, aversive and neutral stimuli in psychiatric disorders. Especially where problems with reward and punishment processing have been implicated in the pathophysiology of the disorder. PMID:27870866
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Yavuzsen, Tugba; Walsh, Declan; Davis, Mellar P; Kirkova, Jordanka; Jin, Tao; LeGrand, Susan; Lagman, Ruth; Bicanovsky, Lesley; Estfan, Bassam; Cheema, Bushra; Haddad, Abdo
2009-12-01
Cancer-related anorexia is traditionally considered part of a complex but ill-defined anorexia-cachexia syndrome in which anorexia is intimately associated with other gastrointestinal (GI) symptoms and weight loss. We surveyed cancer patients with anorexia to learn more about the relationship between anorexia and these symptoms. A 22-item GI questionnaire assessed the severity of anorexia and the prevalence of concurrent GI symptoms, including taste changes, food aversions, altered sense of smell, and diurnal food intake changes. The relationship between anorexia severity and anticancer therapy and prior menstrual or pregnancy-related appetite changes was also assessed. Ninety-five of 101 patients with anorexia surveyed had complete data. Seventy-eight percent of them had moderate or severe anorexia. Abnormal diurnal appetite variation, taste changes, and food aversions were present in over 50% of all those with anorexia. Judged by the numerical rating scale, the worse the anorexia, the more prevalent were early satiety, constipation, vomiting, and food aversions. Those with more severe anorexia had greater weight loss, and worse performance status. Anorexia severity did not correlate with that during prior menses/pregnancy or antitumor therapy. Evaluation of multiple other GI symptoms is important in understanding the total experience of cancer anorexia. Early satiety, taste changes, food aversions, and altered sense of smell are important accompanying GI symptoms. Most validated anorexia tools do not assess these commonly associated GI symptoms. Future research should develop a comprehensive anorexia symptom questionnaire.
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Taste aversion memory reconsolidation is independent of its retrieval.
Rodriguez-Ortiz, Carlos J; Balderas, Israela; Garcia-DeLaTorre, Paola; Bermudez-Rattoni, Federico
2012-10-01
Reconsolidation refers to the destabilization/re-stabilization memory process upon its activation. However, the conditions needed to undergo reconsolidation, as well as its functional significance is quite unclear and a matter of intense investigation. Even so, memory retrieval is held as requisite to initiate reconsolidation. Therefore, in the present work we examined whether transient pharmacological disruption of memory retrieval impedes reconsolidation of stored memory in the widely used associative conditioning task, taste aversion. We found that AMPA receptors inhibition in the amygdala impaired retrieval of taste aversion memory. Furthermore, AMPA receptors blockade impeded retrieval regardless of memory strength. However, inhibition of retrieval did not affect anisomycin-mediated disruption of reconsolidation. These results indicate that retrieval is a dispensable condition to undergo reconsolidation and provide evidence of molecular dissociation between retrieval and activation of memory in the non-declarative memory model taste aversion. Copyright © 2012 Elsevier Inc. All rights reserved.
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Failure to Find Ethanol-Induced Conditioned Taste Aversion in Honey Bees (Apis mellifera L.).
Varnon, Christopher A; Dinges, Christopher W; Black, Timothy E; Wells, Harrington; Abramson, Charles I
2018-04-24
Conditioned taste aversion (CTA) learning is a highly specialized form of conditioning found across taxa that leads to avoidance of an initially neutral stimulus, such as taste or odor, that is associated with, but is not the cause of, a detrimental health condition. This study examines if honey bees (Apis mellifera L.) develop ethanol (EtOH)-induced CTA. Restrained bees were first administered a sucrose solution that was cinnamon scented, lavender scented, or unscented, and contained either 0, 2.5, 5, 10, or 20% EtOH. Then, 30 minutes later, we used a proboscis extension response (PER) conditioning procedure where the bees were taught to associate either cinnamon odor, lavender odor, or an air-puff with repeated sucrose feedings. For some bees, the odor of the previously consumed EtOH solution was the same as the odor associated with sucrose in the conditioning procedure. If bees are able to learn EtOH-induced CTA, they should show an immediate low level of response to odors previously associated with EtOH. We found that bees did not develop CTA despite the substantial inhibitory and aversive effects EtOH has on behavior. Instead, bees receiving a conditioning odor that was previously associated with EtOH showed an immediate high level of response. While this demonstrates bees are capable of one-trial learning common to CTA experiments, this high level of response is the opposite of what would occur if the bees developed a CTA. Responding on subsequent trials also showed a general inhibitory effect of EtOH. Finally, we found that consumption of cinnamon extract reduced the effects of EtOH. The honey bees' lack of learned avoidance to EtOH mirrors that seen in human alcoholism. These findings demonstrate the usefulness of honey bees as an insect model for EtOH consumption. Copyright © 2018 by the Research Society on Alcoholism.
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Swimming-Induced Taste Aversion and Its Prevention by a Prior History of Swimming
ERIC Educational Resources Information Center
Masaki, Takahisa; Nakajima, Sadahiko
2004-01-01
In two experiments, the evidence showed that 20 min of forced swimming by rats caused aversion to a taste solution consumed before swimming. When one of two taste solutions (sodium saccharin or sodium chloride, counterbalanced across rats) was paired with swimming and the other was not, the rats' intakes of these two solutions showed less…
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Davis, Catherine M; de Brugada, Isabel; Riley, Anthony L
2010-05-01
The attenuation of an LiCl-induced conditioned taste aversion (CTA) by LiCl preexposure is mediated primarily by associative blocking via injection-related cues. Given that preexposure to morphine attenuates morphine-induced CTAs, it was of interest to determine whether injection cues also mediate this effect. Certain morphine-induced behaviors such as analgesic tolerance are controlled associatively, via injection-related cues. Accordingly, animals in the present experiments were preexposed to morphine (or vehicle) every other day for five total exposures, followed by an extinction phase, in which the subjects were given saline injections (or no treatment) for 8 (Experiment 1) or 16 (Experiment 2) consecutive days. All of the animals then received five CTA trials with morphine (or vehicle). The morphine-preexposed animals in Experiment 1 displayed an attenuation of the morphine CTA that was unaffected by extinction saline injections, suggesting that blocking by injection cues during morphine preexposure does not mediate this effect. All of the morphine-preexposed subjects in Experiment 2 displayed a weakened preexposure effect, an effect inconsistent with a selective extinction of drug-associated stimuli. The attenuating effects of morphine preexposure in aversion learning are most likely controlled by nonassociative mechanisms, like drug tolerance.
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Monteleone, Alessio Maria; Monteleone, Palmiero; Esposito, Fabrizio; Prinster, Anna; Volpe, Umberto; Cantone, Elena; Pellegrino, Francesca; Canna, Antonietta; Milano, Walter; Aiello, Marco; Di Salle, Francesco; Maj, Mario
2017-07-01
Functional magnetic resonance imaging (fMRI) studies have displayed a dysregulation in the way in which the brain processes pleasant taste stimuli in patients with anorexia nervosa (AN) and bulimia nervosa (BN). However, exactly how the brain processes disgusting basic taste stimuli has never been investigated, even though disgust plays a role in food intake modulation and AN and BN patients exhibit high disgust sensitivity. Therefore, we investigated the activation of brain areas following the administration of pleasant and aversive basic taste stimuli in symptomatic AN and BN patients compared to healthy subjects. Twenty underweight AN women, 20 symptomatic BN women and 20 healthy women underwent fMRI while tasting 0.292 M sucrose solution (sweet taste), 0.5 mM quinine hydrochloride solution (bitter taste) and water as a reference taste. In symptomatic AN and BN patients the pleasant sweet stimulus induced a higher activation in several brain areas than that induced by the aversive bitter taste. The opposite occurred in healthy controls. Moreover, compared to healthy controls, AN patients showed a decreased response to the bitter stimulus in the right amygdala and left anterior cingulate cortex, while BN patients showed a decreased response to the bitter stimulus in the right amygdala and left insula. These results show an altered processing of rewarding and aversive taste stimuli in ED patients, which may be relevant for understanding the pathophysiology of AN and BN. Copyright © 2017 Elsevier Ltd. All rights reserved.
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ERIC Educational Resources Information Center
Hinderliter, Charles F.; Andrews, Amy; Misanin, James R.
2012-01-01
In conditioned taste aversion (CTA), a taste, the conditioned stimulus (CS), is paired with an illness-inducing stimulus, the unconditioned stimulus (US), to produce CS-US associations at very long (hours) intervals, a result that appears to violate the law of contiguity. The specific length of the maximum effective trace interval that has been…
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Mouse model of fragile X syndrome: behavioral and hormonal response to stressors.
Nielsen, Darci M; Evans, Jeffrey J; Derber, William J; Johnston, Kenzie A; Laudenslager, Mark L; Crnic, Linda S; Maclean, Kenneth N
2009-06-01
Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity. Copyright (c) 2009 APA, all rights reserved.
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Conditioned aversion of aluminum sulfate in black ducks
Sparling, D.W.
1990-01-01
Three experiments were conducted to determine if reduced consumption of foods with elevated Al levels by black ducks (Anas rubripes) was due to taste aversion, conditioned taste aversion or malaise. Black ducks preferred a diet with 1,000 ppm Al over a control diet but ate less of a diet with 5,000 ppm Al. Prior experience with the high Al diet enhanced preference for the control diet. Changes in body weight and food consumption through time suggested that aversion to the high Al diet was a conditioned response to mild malaise.
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ERIC Educational Resources Information Center
Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto
2006-01-01
The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…
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Food aversion: a critical balance between allergen-specific IgE levels and taste preference.
Mirotti, Luciana; Mucida, Daniel; de Sá-Rocha, Luis Carlos; Costa-Pinto, Frederico Azevedo; Russo, Momtchilo
2010-03-01
Animals sensitized to allergens change their feeding behavior and avoid drinking the otherwise preferred sweetened solutions containing the allergens. This phenomenon, known as food aversion, appears to be mediated by allergen-specific IgE antibodies. Here we investigated food aversion in BALB/c and C57BL/6 mice, which differ in their allergic responses to the allergen ovalbumin as well as in their preference for sweet taste. BALB/c mice present higher levels of IgE and a natural lower preference for sweet flavors when compared to C57BL/6 mice. Specifically, we studied a conflicting situation in which animals simultaneously experienced the aversive contact with the allergen and the attractive sweet taste of increasing concentrations of sucrose. We found that BALB/c mice were more prone to develop food aversion than C57BL/6 mice and that this aversive behavior could be abolished in both strains by increasing the palatability of the solution containing the allergen. In both strains food aversion was positively correlated with the levels of allergen-specific IgE antibodies and inversely correlated with their preference for sucrose sweetened solutions. 2009 Elsevier Inc. All rights reserved.
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Flax, Shaun M.; Wakeford, Alison G.P.; Cheng, Kejun; Rice, Kenner C.; Riley, Anthony L.
2017-01-01
Rationale The aversive effects of Δ9-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. Objectives The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Methods Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8 and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague Dawley rats. Results The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. Conclusions That norBNI had no significant effect on THC-induced avoidance in adults and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague Dawley rats. PMID:26025420
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Flax, Shaun M; Wakeford, Alison G P; Cheng, Kejun; Rice, Kenner C; Riley, Anthony L
2015-09-01
The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats.
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Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice.
Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W; Proud, Chris G; Rosenblum, Kobi
2012-02-24
Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment. © 2012 Cold Spring Harbor Laboratory Press
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Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat
NASA Technical Reports Server (NTRS)
Fox, Robert A.; Mckenna, Susan
1991-01-01
The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 deg/s. Results are discussed with reference to the use of CTA as a measure of motion-induced 'sickness' or gastrointestinal disturbance, and because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vegal and vestibular functions.
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Sako, N; Shimura, T; Komure, M; Mochizuki, R; Matsuo, R; Yamamoto, T
1994-10-01
Behavioral and electrophysiological experiments were performed to examine the suggestion that rats have two types of carbohydrate taste receptors, one for polysaccharides (e.g., Polycose) and one for common sugars (e.g., sucrose). Qualitative difference between the tastes of Polycose and sugars including sucrose, maltose, glucose, and fructose was surveyed by means of a conditioned taste aversion paradigm in which the number of licks for 20 s to each taste stimulus was measured. Aversive conditioning to Polycose did not generalize to sugars, while aversive conditioning to sucrose generalized to other sugars, but not to Polycose. In the electrophysiological study, taste responses of the whole chorda tympani were recorded. A proteolytic enzyme, pronase E, suppressed nerve responses to both Polycose and sugars to less than 50%. A novel anti-sweet peptide, gurmarin, strongly suppressed responses to sugars, but had essentially no effect on Polycose responses. On the other hand, KHCO3 enhanced responses to sugars to about 300%, but had little effect on Polycose responses. These results have confirmed the notion that rats can differentiate the tastes between Polycose and common sugars and that rats have two types of carbohydrate receptors.
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Sex differences in learning processes of classical and operant conditioning
Dalla, Christina; Shors, Tracey J.
2009-01-01
Males and females learn and remember differently at different times in their lives. These differences occur in most species, from invertebrates to humans. We review here sex differences as they occur in laboratory rodent species. We focus on classical and operant conditioning paradigms, including classical eyeblink conditioning, fear conditioning, active avoidance and conditioned taste aversion. Sex differences have been reported during acquisition, retention and extinction in most of these paradigms. In general, females perform better than males in the classical eyeblink conditioning, in fear-potentiated startle and in most operant conditioning tasks, such as the active avoidance test. However, in the classical fear conditioning paradigm, in certain lever-pressing paradigms and in the conditioned taste aversion males outperform females or are more resistant to extinction. Most sex differences in conditioning are dependent on organizational effects of gonadal hormones during early development of the brain, in addition to modulation by activational effects during puberty and adulthood. Critically, sex differences in performance account for some of the reported effects on learning and these are discussed throughout the review. Because so many mental disorders are more prevalent on one sex than the other, it is important to consider sex differences in learning when applying animal models of learning for these disorders. Finally, we discuss how sex differences in learning continue to alter the brain throughout the lifespan. Thus, sex differences in learning are not only mediated by sex differences in the brain, but also contribute to them. PMID:19272397
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Sex differences in learning processes of classical and operant conditioning.
Dalla, Christina; Shors, Tracey J
2009-05-25
Males and females learn and remember differently at different times in their lives. These differences occur in most species, from invertebrates to humans. We review here sex differences as they occur in laboratory rodent species. We focus on classical and operant conditioning paradigms, including classical eyeblink conditioning, fear-conditioning, active avoidance and conditioned taste aversion. Sex differences have been reported during acquisition, retention and extinction in most of these paradigms. In general, females perform better than males in the classical eyeblink conditioning, in fear-potentiated startle and in most operant conditioning tasks, such as the active avoidance test. However, in the classical fear-conditioning paradigm, in certain lever-pressing paradigms and in the conditioned taste aversion, males outperform females or are more resistant to extinction. Most sex differences in conditioning are dependent on organizational effects of gonadal hormones during early development of the brain, in addition to modulation by activational effects during puberty and adulthood. Critically, sex differences in performance account for some of the reported effects on learning and these are discussed throughout the review. Because so many mental disorders are more prevalent in one sex than the other, it is important to consider sex differences in learning when applying animal models of learning for these disorders. Finally, we discuss how sex differences in learning continue to alter the brain throughout the lifespan. Thus, sex differences in learning are not only mediated by sex differences in the brain, but also contribute to them.
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Marotta, Roberto; Fenu, Sandro; Scheggi, Simona; Vinci, Stefania; Rosas, Michela; Falqui, Andrea; Gambarana, Carla; De Montis, M. Graziella; Acquas, Elio
2014-01-01
Conditioned taste aversion (CTA) can be applied to study associative learning and its relevant underpinning molecular mechanisms in discrete brain regions. The present study examined, by immunohistochemistry and immunocytochemistry, the effects of acquisition and expression of lithium-induced CTA on activated Extracellular signal Regulated Kinase (p-ERK) in the prefrontal cortex (PFCx) and nucleus accumbens (Acb) of male Sprague-Dawley rats. The study also examined, by immunoblotting, whether acquisition and expression of lithium-induced CTA resulted in modified levels of phosphorylation of glutamate receptor subunits (NR1 and GluR1) and Thr34- and Thr75-Dopamine-and-cAMP-Regulated PhosphoProtein (DARPP-32). CTA acquisition was associated with an increase of p-ERK-positive neurons and phosphorylated NR1 receptor subunit (p-NR1) in the PFCx, whereas p-GluR1, p-Thr34- and p-Thr75-DARPP-32 levels were not changed in this brain region. CTA expression increased the number of p-ERK-positive neurons in the shell (AcbSh) and core (AcbC) but left unmodified p-NR1, p-GluR1, p-Thr34- and p-Thr75-DARPP-32 levels. Furthermore, post-embedding immunogold quantitative analysis in AcbSh revealed that CTA expression significantly increased nuclear p-ERK immunostaining as well as p-ERK-labeled axo-spinous contacts. Overall, these results indicate that ERK and NR1, but not GluR1 and DARPP-32, are differentially phosphorylated as a consequence of acquisition and expression of aversive associative learning. Moreover, these results confirm that CTA represents an useful approach to study the molecular basis of associative learning in rats and suggest the involvement of ERK cascade in learning-associated synaptic plasticity. PMID:24847227
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Off-vertical rotation produces conditioned taste aversion and suppressed drinking in mice
NASA Technical Reports Server (NTRS)
Fox, R. A.; Lauber, A. H.; Daunton, N. G.; Phillips, M.; Diaz, L.
1984-01-01
The effects of off-vertical rotation upon the intake of tap water immediately after rotation and upon conditioned taste aversion were assessed in mice with the tilt of the rotation axis varying from 5 to 20 deg from the earth-vertical. Conditioned taste aversion occurred in all mice that were rotated, but the intake of tap water was suppressed only in mice that were rotated at 15 or 20 deg of tilt. The greater suppression of tap-water intake and the stronger conditioned aversion in the mouse as the angle of tilt was increased in this experiment are consistent with predictions from similar experiments with human subjects, where motion sickness develops more rapidly as the angle of tilt is increased. It was suggested that off-vertical rotation may be a useful procedure for insuring experimental control over vestibular stimulation in animal studies of motion sickness.
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Alcohol-Aversion Therapy: Relation Between Strength of Aversion and Abstinence.
ERIC Educational Resources Information Center
Cannon, Dale S.; And Others
1986-01-01
Assessed degree of alcohol aversion in 60 alcoholics who received emetic alcohol-aversion therapy. Results revealed changes in response to alcoholic, but not to nonalcoholic, flavors, including decreased consumption in taste tests, more negative flavor ratings, overt behavioral indicants of aversion and increased tachycardiac response. (Author/NB)
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ERIC Educational Resources Information Center
De la Casa, L. G.; Mena, A.; Orgaz, A.; Fernandez, A.
2013-01-01
Contextual specificity of Latent Inhibition (LI) has been demonstrated using an ample range of experimental procedures. Context dependence has not been consistently obtained, however, when LI has been induced using a Conditioned Taste Aversion (CTA) procedure. This paper presents two experiments designed to analyze whether the context plays the…
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ERIC Educational Resources Information Center
Guzman-Ramos, Kioko; Osorio-Gomez, Daniel; Moreno-Castilla, Perla; Bermudez-Rattoni, Federico
2012-01-01
Amygdala activity mediates the acquisition and consolidation of emotional experiences; we have recently shown that post-acquisition reactivation of this structure is necessary for the long-term storage of conditioned taste aversion (CTA). However, the specific neurotransmitters involved in such reactivation are not known. The aim of the present…
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Hadamitzky, Martin; Orlowski, Kathrin; Schwitalla, Jan Claudius; Bösche, Katharina; Unteroberdörster, Meike; Bendix, Ivo; Engler, Harald; Schedlowski, Manfred
2016-09-01
Conditioned responses gradually weaken and eventually disappear when subjects are repeatedly exposed to the conditioned stimulus (CS) in the absence of the unconditioned stimulus (US), a process called extinction. Studies have demonstrated that extinction of conditioned taste aversion (CTA) can be prevented by interfering with protein synthesis in the insular cortex (IC). However, it remained unknown whether it is possible to pharmacologically stabilize the taste aversive memory trace over longer periods of time. Thus, the present study aimed at investigating the time frame during which extinction of CTA can be efficiently prevented by blocking protein synthesis in the IC. Employing an established conditioning paradigm in rats with saccharin as CS, and the immunosuppressant cyclosporine A (CsA) as US, we show here that daily bilateral intra-insular injections of the protein synthesis inhibitor anisomycin (120μg/μl) immediately after retrieval significantly diminished CTA extinction over a period of five retrieval days and subsequently reached levels of saline-infused controls. These findings demonstrate that it is possible to efficiently delay but not to fully prevent CTA extinction during repeated retrieval trials by blocking protein translation with daily bilateral infusions of anisomycin in the IC. These data confirm and extent earlier reports indicating that the role of protein synthesis in CTA extinction learning is not limited to gastrointestinal malaise-inducing drugs such as lithium chloride (LiCl). Copyright © 2016 Elsevier Inc. All rights reserved.
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Effect of Flumethrin on Survival and Olfactory Learning in Honeybees
Tan, Ken; Yang, Shuang; Wang, Zhengwei; Menzel, Randolf
2013-01-01
Flumethrin has been widely used as an acaricide for the control of Varroa mites in commercial honeybee keeping throughout the world for many years. Here we test the mortality of the Asian honeybee Apis cerana cerana after treatment with flumethrin. We also ask (1) how bees react to the odor of flumethrin, (2) whether its odor induces an innate avoidance response, (3) whether its taste transmits an aversive reinforcing component in olfactory learning, and (4) whether its odor or taste can be associated with reward in classical conditioning. Our results show that flumethrin has a negative effect on Apis ceranàs lifespan, induces an innate avoidance response, acts as a punishing reinforcer in olfactory learning, and interferes with the association of an appetitive conditioned stimulus. Furthermore flumethrin uptake within the colony reduces olfactory learning over an extended period of time. PMID:23785490
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Pontine and Thalamic Influences on Fluid Rewards: II. Sucrose and Corn Oil Conditioned Aversions
Liang, Nu-Chu; Grigson, Patricia S.; Norgren, Ralph
2011-01-01
In this study conditioned aversions were produced in sham feeding rats to limit postingestive feedback from the oral stimulus. All control rats learned an aversion to either 100% corn oil or 0.3M sucrose when ingestion of these stimuli was followed by an injection of lithium chloride (LiCl). Rats with lesions of the ventroposteromedial thalamus also learned to avoid either corn oil or sucrose. After 3 trials, rats with damage to the parabrachial nuclei (PBN) learned to avoid 100% corn oil, but failed to do so when the stimulus was 0.3M sucrose. These results support our hypothesis that the PBN is necessary to appropriately respond to a taste, but not an oil cue as a function of experience (i.e., pairings with LiCl). The results also are consistent with our results from operant tasks demonstrating that the trigeminal thalamus, the ventroposteromedial nucleus, is not required for responding to the rewarding properties of sucrose, oil, or for modifying the response to these stimuli as a function of experience. PMID:21699909
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Bachmanov, Alexander A.; Li, Xia; Li, Shanru; Neira, Mauricio; Beauchamp, Gary K.; Azen, Edwin A.
2013-01-01
An acetylated sugar, sucrose octaacetate (SOA), tastes bitter to humans and has an aversive taste to at least some mice and other animals. In mice, taste aversion to SOA depends on allelic variation of a single locus, Soa. Three Soa alleles determine ‘taster’ (Soaa), ‘nontaster’ (Soab), and ‘demitaster’ (Soac) phenotypes of taste sensitivity to SOA. Although Soa has been mapped to distal Chromosome (Chr) 6, the limits of the Soa region have not been defined. In this study, mice from congenic strains SW.B6-Soab, B6.SW-Soaa, and C3.SW-Soaa/c and from an outbred CFW strain were genotyped with polymorphic markers on Chr 6. In the congenic strains, the limits of introgressed donor fragments were determined. In the outbred mice, linkage disequilibrium and haplotype analyses were conducted. Positions of the markers were further resolved by using radiation hybrid mapping. The results show that the Soa locus is contained in a ~1-cM (3.3–4.9 Mb) region including the Prp locus. PMID:11641717
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ERIC Educational Resources Information Center
Ishii, Kiyoshi; Iguchi, Yoshio; Fukumoto, Kazuya; Nakayasu, Tomohiro
2008-01-01
Using a conditioned taste aversion procedure with rats as the subjects, two experiments examined the effect of presenting a conditioned stimulus (CS saccharin solution) in one context followed by an unconditioned stimulus (US LiCl) in a different context. Experiment 1 showed that animals which received the above-mentioned procedure (Group D)…
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NASA Technical Reports Server (NTRS)
Rabin, B. M.; Joseph, J. A.; Erat, S.
1998-01-01
The effects of exposure to ionizing radiation on behavior may result from effects on peripheral or on central systems. For behavioral endpoints that are mediated by peripheral systems (e.g., radiation-induced conditioned taste aversion or vomiting), the behavioral effects of exposure to heavy particles (56Fe, 600 MeV/n) are qualitatively similar to the effects of exposure to gamma radiation (60Co) and to fission spectrum neutrons. For these endpoints, the only differences between the different types of radiation are in terms of relative behavioral effectiveness. For behavioral endpoints that are mediated by central systems (e.g., amphetamine-induced taste aversion learning), the effects of exposure to 56Fe particles are not seen following exposure to lower LET gamma rays or fission spectrum neutrons. These results indicate that the effects of exposure to heavy particles on behavioral endpoints cannot necessarily be extrapolated from studies using gamma rays, but require the use of heavy particles.
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Arias, Carlos; Pautassi, Ricardo Marcos; Molina, Juan Carlos; Spear, Norman E
2010-09-01
Adult rats display taste avoidance and disgust reactions when stimulated with gustatory stimuli previously paired with aversive agents such as lithium chloride (LiCl). By the second postnatal week of life, preweanling rats also display specific behaviors in response to a tastant conditioned stimulus (CS) that predicts LiCl-induced malaise. The present study compared conditioned disgust reactions induced by LiCl or ethanol (EtOH) in preweanling rats. In Experiment 1 we determined doses of ethanol and LiCl that exert similar levels of conditioned taste avoidance. After having equated drug dosage in terms of conditioned taste avoidance, 13-day-old rats were given a single pairing of a novel taste (saccharin) and either LiCl or ethanol (2.5 g/kg; Experiment 2). Saccharin intake and emission of disgust reactions were assessed 24 and 48 hr after training. Pups given paired presentations of saccharin and the aversive agents (ethanol or LiCl) consumed less saccharin during the first testing day than controls. These pups also showed more aversive behavioral reactions to the gustatory CS than controls. Specifically, increased amounts of grooming, general activity, head shaking, and wall climbing as well as reduced mouthing were observed in response to the CS. Conditioned aversive reactions but not taste avoidance were still evident on the second testing day. In conclusion, a taste CS paired with postabsorptive effects of EtOH and LiCl elicited a similar pattern of conditioned rejection reactions in preweanling rats. These results suggest that similar mechanisms may be underlying CTAs induced by LiCl and a relatively high EtOH dose.
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AAB and ABA Renewal as a Function of the Number of Extinction Trials in Conditioned Taste Aversion
ERIC Educational Resources Information Center
Rosas, Juan M.; Garcia-Gutierrez, Ana; Callejas-Aguilera, Jose E.
2007-01-01
Three experiments explored renewal in conditioned taste aversion after different amounts of extinction. In Experiment 1, three groups of rats received a single conditioning trial where a saccharin solution was paired with LiCl, followed by 3 extinction trials, and a two-trial test. Groups differed in the context where they received each of the…
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ERIC Educational Resources Information Center
Akirav, Irit; Khatsrinov, Vicktoria; Vouimba, Rose-Marie; Merhav, Maayan; Ferreira, Guillaume; Rosenblum, Kobi; Maroun, Mouna
2006-01-01
We investigated the role of the ventromedial prefrontal cortex (vmPFC) in extinction of conditioned taste aversion (CTA) by microinfusing a protein synthesis inhibitor or N-methyl-d-asparate (NMDA) receptors antagonist into the vmPFC immediately following a non-reinforced extinction session. We found that the protein synthesis blocker anisomycin,…
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Davis, Catherine M; Rice, Kenner C; Riley, Anthony L
2009-10-01
The Fischer 344 (F344) and Lewis (LEW) inbred rat strains react differently to morphine in a number of behavioral and physiological preparations, including the acquisition of aversions induced by this compound. The present experiment tested the ability of various compounds with relative selectivity at kappa, delta and mu receptor subtypes to assess the relative roles of these subtypes in mediating the differential aversive effects of morphine in the two strains. In the assessment of the role of the kappa receptor in morphine-induced aversions, animals in both strains were given access to saccharin followed by varying doses of the kappa agonist (-)-U50,488H (0.0, 0.28, 0.90 and 1.60 mg/kg). Although (-)-U50,488H induced aversions in both strains, no strain differences emerged. A separate subset of subjects was trained with the selective delta opioid agonist, SNC80 (0.0, 5.6, 10.0 and 18.0 mg/kg), and again although SNC80 induced aversions, there were no strain differences. Finally, a third subset of subjects was trained with heroin (0.0, 3.2, 5.6 and 10.0 mg/kg), a compound with activity at all three opiate receptor subtypes. Although heroin induced aversions in both strains, the aversions were significantly greater in the F344 strain, suggesting that differential activation of the mu opioid receptor likely mediates the reported strain differences in morphine-induced aversion learning. These data were discussed in terms of strain differences in opioid system functioning and the implications of such differences for other morphine-induced behavioral effects reported in F344 and LEW rats.
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Risco, Severiano; Mediavilla, Cristina
2014-11-01
Previous studies demonstrated that the intracerebroventricular administration of SB-334867-A, a selective antagonist of orexin OX1R receptors, blocks the acquisition of saccharin-induced conditioned flavor preference (CFP) but not LiCl-induced taste aversion learning (TAL). Orexinergic fibers from the lateral hypothalamus end in the central nucleus of the amygdala (CeA), which expresses orexin OX1R receptors. Taste and sensory inputs also are present in CeA, which may contribute to the development of taste learning. This study analyzed the effect of two doses (1.5 and 6μg/0.5μl) of SB-334867-A administered into the CeA on flavor-taste preference induced by saccharin and on TAL induced by a single administration of LiCl (0.15M, 20ml/kg, i.p.). Outcomes indicate that inactivation of orexinergic receptors in the CeA attenuates flavor-taste preference in a two-bottle test (saccharin vs. water). Intra-amygdalar SB-334867-A does not affect gustatory processing or the preference for the sweet taste of saccharin given that SB-334867-A- and DMSO-treated groups (control animals) increased the intake of the saccharin-associated flavor across training acquisition sessions. Furthermore, SB-334867-A in the CeA does not block TAL acquisition ruling out the possibility that functional inactivation of OX1R receptors interferes with taste processing. Orexin receptors in the CeA appear to intervene in the association of a flavor with orosensory stimuli, e.g., a sweet and pleasant taste, but could be unnecessary when the association is established with visceral stimuli, e.g., lithium chloride. These data suggest that orexinergic projections to the CeA may contribute to the reinforcing signals facilitating the acquisition of taste learning and the change in hedonic evaluation of the taste, which would have important implications for the OX1R-targeted pharmacological treatment of eating disorders. Copyright © 2014 Elsevier Inc. All rights reserved.
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Plasticity in the Interoceptive System.
Torrealba, Fernando; Madrid, Carlos; Contreras, Marco; Gómez, Karina
2017-01-01
The most outstanding manifestations of the plastic capacities of brain circuits and their neuronal and synaptic components in the adult CNS are learning and memory. A reduced number of basic plastic mechanisms underlie learning capacities at many levels and regions of the brain. The interoceptive system is no exception, and some of the most studied behavioral changes that involve learning and memory engage the interoceptive pathways at many levels of their anatomical and functional organization.In this chapter, we will review four examples of learning, mostly in rats, where the interoceptive system has a role. In the case of conditioned taste aversion, the interoceptive system is of outstanding importance. In drug addiction, the role of the insular cortex - the highest level of the interoceptive system- is unusual and complex, as many forebrain regions are engaged by the process of addiction. In the third example, neophobia, the gustatory region of the insular cortex plays a major role. Finally, the role of different areas of the insular cortex in different processes of aversive memory, particularly fear conditioning, will be reviewed.
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Economic Constraints on Taste Formation and the True Cost of Healthy Eating
Daniel, Caitlin
2015-01-01
This paper shows how an interaction between economic constraints and children’s taste preferences shapes low-income families’ food decisions. According to studies of eating behavior, children often refuse unfamiliar foods 8 to 15 times before accepting them. Using 80 interviews and 41 grocery-shopping observations with 73 primary caregivers in the Boston area in 2013–2015, I find that many low-income respondents minimize the risk of food waste by purchasing what their children like—often calorie-dense, nutrient-poor foods. High-income study participants, who have greater resources to withstand the cost of uneaten food, are more likely to repeatedly introduce foods that their children initially refuse. Several conditions moderate the relationship between children’s taste aversion and respondents’ risk aversion, including household-level food preferences, respondents’ conceptions of adult authority, and children’s experiences outside of the home. Low-income participants’ risk aversion may affect children’s taste acquisition and eating habits, with implications for socioeconomic disparities in diet quality. This paper proposes that the cost of providing children a healthy diet may include the possible cost of foods that children waste as they acquire new tastes. PMID:26650928
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Economic constraints on taste formation and the true cost of healthy eating.
Daniel, Caitlin
2016-01-01
This article shows how an interaction between economic constraints and children's taste preferences shapes low-income families' food decisions. According to studies of eating behavior, children often refuse unfamiliar foods 8 to 15 times before accepting them. Using 80 interviews and 41 grocery-shopping observations with 73 primary caregivers in the Boston area in 2013-2015, I find that many low-income respondents minimize the risk of food waste by purchasing what their children like--often calorie-dense, nutrient-poor foods. High-income study participants, who have greater resources to withstand the cost of uneaten food, are more likely to repeatedly introduce foods that their children initially refuse. Several conditions moderate the relationship between children's taste aversion and respondents' risk aversion, including household-level food preferences, respondents' conceptions of adult authority, and children's experiences outside of the home. Low-income participants' risk aversion may affect children's taste acquisition and eating habits, with implications for socioeconomic disparities in diet quality. This article proposes that the cost of providing children a healthy diet may include the possible cost of foods that children waste as they acquire new tastes. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Uematsu, Akira; Kitamura, Akihiko; Iwatsuki, Ken; Uneyama, Hisayuki; Tsurugizawa, Tomokazu
2015-09-01
Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby animals associate tastes with subsequent visceral illness. The prelimbic cortex (PL) has been shown to be involved in the association of events separated by time. However, the nature of PL activity and its functional network in the whole brain during CTA learning remain unknown. Here, using awake functional magnetic resonance imaging and fiber tracking, we analyzed functional brain connectivity during the association of tastes and visceral illness. The blood oxygen level-dependent (BOLD) signal significantly increased in the PL after tastant and lithium chloride (LiCl) infusions. The BOLD signal in the PL significantly correlated with those in the amygdala and agranular insular cortex (IC), which we found were also structurally connected to the PL by fiber tracking. To precisely examine these data, we then performed double immunofluorescence with a neuronal activity marker (c-Fos) and an inhibitory neuron marker (GAD67) combined with a fluorescent retrograde tracer in the PL. During CTA learning, we found an increase in the activity of excitatory neurons in the basolateral amygdala (BLA) or agranular IC that project to the PL. Taken together, these findings clearly identify a role of synchronized PL, agranular IC, and BLA activity in CTA learning. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Burying by rats in response to aversive and nonaversive stimuli
Poling, Alan; Cleary, James; Monaghan, Michael
1981-01-01
Previous investigations have shown that rats bury a variety of conditioned and unconditioned aversive stimuli. Such burying has been considered as a species-typical defensive reaction. In the present studies, rats buried spouts filled with Tabasco sauce, or condensed milk to which a taste aversion was conditioned, but did not bury water-filled spouts or spouts filled with a palatable novel food (apple juice) to which a taste aversion was not conditioned. However, in other experiments rats consistently and repeatedly buried Purina Rat Chow, Purina Rat Chow coated with quinine, and glass marbles. This indicates that a variety of stimuli, not all aversive or novel, evoke burying by rats. Whereas the behavior may reasonably be considered as a species-typical defensive behavior in some situations, the wide range of conditions that occasion burying suggests that the behavior has no single biological function. PMID:16812198
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Mickley, G. Andrew; Hoxha, Nita; Luchsinger, Joseph L.; Rogers, Morgan M.; Wiles, Nathanael R.
2013-01-01
Elevation of brain magnesium enhances synaptic plasticity and extinction of conditioned fear memories. This experiment examined the generalizability of this phenomenon by studying the effects of a novel magnesium compound, magnesium-L-threonate (MgT), on conditioned taste aversion (CTA) extinction and spontaneous recovery (SR). Adult male Sprague-Dawley rats were maintained on a 23-hour water deprivation cycle and acquired a CTA following the taste of a CS [0.3% saccharin + 16mg/ml MgT (SAC+MgT)] paired with a US [81 mg/kg (i.p.) Lithium Chloride (LiCl)]. Following CTA acquisition, rats drank a water + MgT solution for up to 1 hour/day over the next 31 days. For 14 additional days, some animals continued water + MgT treatment, but others drank water only to allow MgT to be eliminated from the body. We then employed 2 different extinction paradigms: (1) CS-Only (CSO), in which SAC was presented, every-other day, or (2) Explicitly Unpaired (EU), in which both SAC and LiCl were presented, but on alternate days. EU extinction procedures have been shown to speed CTA extinction and reduce spontaneous recovery of the aversion. Throughout extinction, half of the rats in each group continued to drink MgT (now in SAC or supplemental water+MgT solution), whereas the other half drank SAC only/water only until SAC drinking reached ≥ 90% of baseline (asymptotic extinction). Rats receiving MgT just before/during extinction drank less SAC on the first day of extinction suggesting that they had retained a stronger CTA. MgT enhanced the rate of extinction. Furthermore, the MgT-treated rats showed a relatively modest SR of the CTA 30 days later – indicating that the extinction procedure was more effective for these animals. Our data suggest that long-term dietary MgT may enhance the consolidation/retention of a CTA, speed extinction, and inhibit SR of this learned aversion. PMID:23474371
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Reciprocal Relationships Between the Immune and Central Nervous System
1990-05-01
grovth factor B2, corticoster ", oids, IFN-y, conditioned taste aversion, schedule-cont rolled I Ibehavior, prostaglandin ., cPA yr s P oq/c.1oý w 19...on conditioned taste ’- & aversion, but they both inhibit the reductions in social exploration and scheddle-controlled behavior of rats injected...secreted by the pituitary gland. These findings probably at least partially explain why elderly persons cannot develop adequate fevers and are at risk
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Taraschenko, Olga D.; Maisonneuve, Isabelle M.; Glick, Stanley D.
2015-01-01
18-Methoxycoronaridine (18-MC), a selective antagonist of α3β4 nicotinic receptors, has been shown to reduce the self-administration of several drugs of abuse. Recently, this agent has also been shown to attenuate sucrose reward, decrease sucrose intake and prevent the development of sucrose-induced obesity in rats. The present experiments were designed to determine whether the latter effect was due to an 18-MC-induced conditioned taste aversion to sucrose. Both 18-MC (20 mg/ kg, i.p.) and control agent, lithium chloride (100 mg/kg, i.p.), reduced sucrose intake 24 h after association with sucrose; however, only lithium chloride reduced sucrose intake 72h later. Consistent with previous data, 18-MC appears to have proactive effect for 24h and it does not induce a conditioned taste aversion. PMID:20457177
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Delta receptor antagonism, ethanol taste reactivity, and ethanol consumption in outbred male rats.
Higley, Amanda E; Kiefer, Stephen W
2006-11-01
Naltrexone, a nonspecific opioid antagonist, produces significant changes in ethanol responsivity in rats by rendering the taste of ethanol aversive as well as producing a decrease in voluntary ethanol consumption. The present study investigated the effect of naltrindole, a specific antagonist of delta opioid receptors, on ethanol taste reactivity and ethanol consumption in outbred rats. In the first experiment, rats received acute treatment of naltrexone, naltrindole, or saline followed by the measurement of ethanol consumption in a short-term access period. The second experiment involved the same treatments and investigated ethanol palatability (using the taste-reactivity test) as well as ethanol consumption. Results indicated that treatment with 3 mg/kg naltrexone significantly affected palatability (rendered ethanol more aversive, Experiment 2) and decreased voluntary ethanol consumption (Experiments 1 and 2). The effects of naltrindole were inconsistent. In Experiment 1, 8 mg/kg naltrindole significantly decreased voluntary ethanol consumption but this was not replicated in Experiment 2. The 8 mg/kg dose produced a significant increase in aversive responding (Experiment 2) but did not affect ingestive responding. Lower doses of naltrindole (2 and 4 mg/kg) were ineffective in altering rats' taste-reactivity response to and consumption of ethanol. While these data suggest that delta receptors are involved in rats' taste-reactivity response to ethanol and rats' ethanol consumption, it is likely that multiple opioid receptors mediate both behavioral responses.
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Insular Cortex Is Involved in Consolidation of Object Recognition Memory
ERIC Educational Resources Information Center
Bermudez-Rattoni, Federico; Okuda, Shoki; Roozendaal, Benno; McGaugh, James L.
2005-01-01
Extensive evidence indicates that the insular cortex (IC), also termed gustatory cortex, is critically involved in conditioned taste aversion and taste recognition memory. Although most studies of the involvement of the IC in memory have investigated taste, there is some evidence that the IC is involved in memory that is not based on taste. In…
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Investigating motion sickness using the conditioned taste aversion paradigm
NASA Technical Reports Server (NTRS)
Fox, Robert A.
1991-01-01
The avoidance of foods which are associated with uncomfortable or aversive internal states has long been recognized. Many people are aware, either directly or via anecdotal reports, of individuals who avoid foods which were eaten just before the onset of sickness. Awareness of this phenomenon can be traced to the writings of John Locke. The disruption of diet during cancer therapy is sometimes ascribed to the attribution of an unpleasant quality to foods eaten preceding the sickness induced by therapy itself. In addition, it has long been recognized by the manufacturers of rodent poisons that animals avoid the injection of food treated with nonlethal doses of poison. An important part of the laboratory study of this phenomenon was directed toward studying the role learning plays in this type of avoidance behavior. Following the lead of Garcia and his associates, this avoidance has come to be interpreted as arising from a form of classical conditioning. In typical laboratory studies of this bahavior, a novel food is ingested just prior to exposure to some stimulus, commonly poisoning or irradiation, which produces illness. Following the terminology of classical conditioning, it is common to describe this procedure as one of 'pairing' a conditioned stimulus (CS), the novel food, with an unconditioned stimulus (US), the illness induced by toxicosis or irradiation. Avoidance of the food in succeeding feeding opportunities is viewed as a learned response or a conditioned taste aversion (CTA). Garcia et al. asserted that motion sickness could produce 'gustatory' aversions, but passive motion was first reported as an US to establish CTA by Green and Rachlin. The purpose is to review the manner in which CTA has been used to study motion sickness. Numerous reviews concentrating on other aspects of CTA are available in the existing literature. Readers are encouraged to consult the various papers and edited books for extensive information on other aspects of this literature.
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Gonzalez, Maria Carolina; Villar, Maria Eugenia; Igaz, Lionel M; Viola, Haydée; Medina, Jorge H
2015-12-01
The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions. Copyright © 2015 Elsevier Inc. All rights reserved.
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A high-protein diet enhances satiety without conditioned taste aversion in the rat.
Bensaïd, Ahmed; Tomé, Daniel; L'Heureux-Bourdon, Diane; Even, Patrick; Gietzen, Dorothy; Morens, Céline; Gaudichon, Claire; Larue-Achagiotis, Christiane; Fromentin, Gilles
2003-02-01
In order to determine the respective roles of conditioned food aversion, satiety and palatability, we studied behavioral responses to a 50% total milk protein diet, compared with those to a normal protein diet containing 14% total milk protein. Different paradigms were employed, including meal pattern analysis, two-choice testing, flavor testing, a behavioral satiety sequence (BSS) and taste reactivity. Our experiments showed that only behavioral and food intake parameters were disturbed during the first day when an animal ate the high-protein (P50) diet, and that most parameters returned to baseline values as soon as the second day of P50. Rats adapted to P50 did not acquire a conditioned taste aversion (CTA) but exhibited satiety, and a normal BSS. The initial reduction in high-protein diet intake appeared to result from the lower palatability of the food combined with the satiety effect of the high-protein diet and the delay required for metabolic adaptation to the higher protein level.
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Yoshida, Takashi; Monk, Kevin J.; Katz, Donald B.
2013-01-01
The taste of foods, in particular the palatability of these tastes, exerts a powerful influence on our feeding choices. Although the lateral hypothalamus (LH) has long been known to regulate feeding behavior, taste processing in LH remains relatively understudied. Here, we examined single-unit LH responses in rats subjected to a battery of taste stimuli that differed in both chemical composition and palatability. Like neurons in cortex and amygdala, LH neurons produced a brief epoch of nonspecific responses followed by a protracted period of taste-specific firing. Unlike in cortex, however, where palatability-related information only appears 500 ms after the onset of taste-specific firing, taste specificity in LH was dominated by palatability-related firing, consistent with LH's role as a feeding center. Upon closer inspection, taste-specific LH neurons fell reliably into one of two subtypes: the first type showed a reliable affinity for palatable tastes, low spontaneous firing rates, phasic responses, and relatively narrow tuning; the second type showed strongest modulation to aversive tastes, high spontaneous firing rates, protracted responses, and broader tuning. Although neurons producing both types of responses were found within the same regions of LH, cross-correlation analyses suggest that they may participate in distinct functional networks. Our data shed light on the implementation of palatability processing both within LH and throughout the taste circuit, and may ultimately have implications for LH's role in the formation and maintenance of taste preferences and aversions. PMID:23719813
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Li, Jennifer X; Yoshida, Takashi; Monk, Kevin J; Katz, Donald B
2013-05-29
The taste of foods, in particular the palatability of these tastes, exerts a powerful influence on our feeding choices. Although the lateral hypothalamus (LH) has long been known to regulate feeding behavior, taste processing in LH remains relatively understudied. Here, we examined single-unit LH responses in rats subjected to a battery of taste stimuli that differed in both chemical composition and palatability. Like neurons in cortex and amygdala, LH neurons produced a brief epoch of nonspecific responses followed by a protracted period of taste-specific firing. Unlike in cortex, however, where palatability-related information only appears 500 ms after the onset of taste-specific firing, taste specificity in LH was dominated by palatability-related firing, consistent with LH's role as a feeding center. Upon closer inspection, taste-specific LH neurons fell reliably into one of two subtypes: the first type showed a reliable affinity for palatable tastes, low spontaneous firing rates, phasic responses, and relatively narrow tuning; the second type showed strongest modulation to aversive tastes, high spontaneous firing rates, protracted responses, and broader tuning. Although neurons producing both types of responses were found within the same regions of LH, cross-correlation analyses suggest that they may participate in distinct functional networks. Our data shed light on the implementation of palatability processing both within LH and throughout the taste circuit, and may ultimately have implications for LH's role in the formation and maintenance of taste preferences and aversions.
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Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa.
Cowdrey, Felicity A; Park, Rebecca J; Harmer, Catherine J; McCabe, Ciara
2011-10-15
Recent evidence has shown that individuals with acute anorexia nervosa and those recovered have aberrant physiological responses to rewarding stimuli. We hypothesized that women recovered from anorexia nervosa would show aberrant neural responses to both rewarding and aversive disorder-relevant stimuli. Using functional magnetic resonance imaging (fMRI), the neural response to the sight and flavor of chocolate, and their combination, in 15 women recovered from restricting-type anorexia nervosa and 16 healthy control subjects matched for age and body mass index was investigated. The neural response to a control aversive condition, consisting of the sight of moldy strawberries and a corresponding unpleasant taste, was also measured. Participants simultaneously recorded subjective ratings of "pleasantness," "intensity," and "wanting." Despite no differences between the groups in subjective ratings, individuals recovered from anorexia nervosa showed increased neural response to the pleasant chocolate taste in the ventral striatum and pleasant chocolate sight in the occipital cortex. The recovered participants also showed increased neural response to the aversive strawberry taste in the insula and putamen and to the aversive strawberry sight in the anterior cingulate cortex and caudate. Individuals recovered from anorexia nervosa have increased neural responses to both rewarding and aversive food stimuli. These findings suggest that even after recovery, women with anorexia nervosa have increased salience attribution to food stimuli. These results aid our neurobiological understanding and support the view that the neural response to reward may constitute a neural biomarker for anorexia nervosa. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.
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Ethanol-induced conditioned taste avoidance: reward or aversion?
Liu, Chuang; Showalter, John; Grigson, Patricia Sue
2009-03-01
Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague-Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. The results suggest that the suppressive effects of ethanol on CS intake are mediated by both rewarding and aversive consequences, varying as a function of dose.
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Yoshida, Yuta; Kawabata, Fuminori; Kawabata, Yuko; Nishimura, Shotaro; Tabata, Shoji
2018-07-01
Umami taste is one of the five basic tastes (sweet, umami, bitter, sour, and salty), and is elicited by l-glutamate salts and 5'-ribonucleotides. In chickens, the elucidation of the umami taste sense is an important step in the production of new feedstuff for the animal industry. Although previous studies found that chickens show a preference for umami compounds in long-term behavioral tests, there are limitations to our understanding of the role of the umami taste sense in chicken oral tissues because the long-term tests partly reflected post-ingestive effects. Here, we performed a short-term test and observed agonists of chicken umami taste receptor, l-alanine and l-serine, affected the solution intakes of chickens. Using this method, we found that chickens could respond to umami solutions containing monosodium l-glutamate (MSG) + inosine 5'-monophosphate (IMP) within 5 min. We also demonstrated that chickens were successfully conditioned to avoid umami solution by the conditioned taste aversion test. It is noted that conditioning to umami solution was generalized to salty and sweet solutions. Thus, chickens may perceive umami taste as a salty- and sweet-like taste. In addition, we found that umami taste receptor candidates were differentially expressed in different regions of the chicken oral tissues. Taken together, the present results strongly suggest that chickens have a sense of umami taste and have umami taste receptors in their oral tissue. Copyright © 2018 Elsevier Inc. All rights reserved.
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Dyr, Wanda; Wyszogrodzka, Edyta; Paterak, Justyna; Siwińska-Ziółkowska, Agnieszka; Małkowska, Anna; Polak, Piotr
2016-03-01
The aversive action of the pharmacological properties of ethanol was studied in selectively bred Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats. For this study, a conditioned-taste aversion test was used. Male WHP and WLP rats were submitted to daily 20-min sessions for 5 days, in which a saccharin solution (1.0 g/L) was available (pre-conditioning phase). Next, this drinking was paired with the injection of ethanol (0, 0.5, 1.0 g/kg), intraperitoneally [i.p.] immediately after removal of the saccharin bottle (conditioning phase). Afterward, the choice between the saccharin solution and water was extended for 18 subsequent days for 20-min daily sessions (post-conditioning phase). Both doses of ethanol did not produce an aversion to saccharin in WLP and WHP rats in the conditioning phase. However, injection of the 1.0 g/kg dose of ethanol produced an aversion in WLP rats that was detected by a decrease in saccharin intake at days 1, 3, 7, and 10 of the post-conditioning phase, with a decrease in saccharin preference for 16 days of the post-conditioning phase. Conditioned taste aversion, measured as a decrease in saccharin intake and saccharin preference, was only visible in WHP rats at day 1 and day 3 of the post-conditioning phase. This difference between WLP and WHP rats was apparent despite similar blood ethanol levels in both rat lines following injection of 0.5 and 1.0 g/kg of ethanol. These results may suggest differing levels of aversion to the post-ingestional effects of ethanol between WLP and WHP rats. These differing levels of aversion may contribute to the selected line difference in ethanol preference in WHP and WLP rats. Copyright © 2016 Elsevier Inc. All rights reserved.
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Rewarding and aversive effects of nicotine are segregated within the nucleus accumbens.
Sellings, Laurie H L; Baharnouri, Golriz; McQuade, Lindsey E; Clarke, Paul B S
2008-07-01
Forebrain dopamine plays a critical role in motivated behavior. According to the classic view, mesolimbic dopamine selectively guides behavior motivated by positive reinforcers. However, this has been challenged in favor of a wider role encompassing aversively motivated behavior. This controversy is particularly striking in the case of nicotine, with opposing claims that either the rewarding or the aversive effect of nicotine is critically dependent on mesolimbic dopamine transmission. In the present study, the effects of 6-hydroxydopamine lesions of nucleus accumbens core vs. medial shell on intravenous nicotine conditioned place preference and conditioned taste aversion were examined in male adult rats. Dopaminergic denervation in accumbens medial shell was associated with decreased nicotine conditioned place preference. Conversely, denervation in accumbens core was associated with an increase in conditioned place preference. In addition, dopaminergic denervation of accumbens core but not medial shell abolished conditioned taste aversion for nicotine. We conclude that nucleus accumbens core and medial shell dopaminergic innervation exert segregated effects on rewarding and aversive effects of nicotine. More generally, our findings indicate that dopaminergic transmission may mediate or enable opposing motivational processes within functionally distinct domains of the accumbens.
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The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.
Rinker, Jennifer A; Busse, Gregory D; Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L
2008-04-01
Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use. Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design. Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined. Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination. These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.
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Loney, Gregory C; Meyer, Paul J
2018-03-01
Aversion to the orosensory properties of concentrated ethanol (EtOH) solutions is often cited as a primary barrier to initiation of drinking and may contribute to abstention. These aversive properties include gustatory processes which encompass both bitter-like taste qualities and trigeminal-mediated irritation. Chronic intermittent EtOH access (CIA) results in substantial and persistent increases in EtOH consumption, but the degree to which this facilitation involves sensory responding to EtOH and other bitter stimuli is currently undetermined. Long-Evans rats were given brief-access licking tests designed to examine the immediate, taste-guided assessment of the palatability of EtOH and quinine solutions. Rats were assessed once in a naïve state and again following previous brief-access exposure, or following 4 weeks of CIA. The relationship between the sensitivity to the aversive orosensory properties of EtOH and quinine following EtOH access and the impact of antecedent quinine exposure on the acceptance of EtOH were determined in 2 parallel studies. Both brief access to EtOH and 4-week CIA resulted in substantial rightward shifts in the concentration-response function of brief-access EtOH licking, indicating that EtOH exposure increased acceptance of the taste of EtOH. The initial sensitivity to the aversive orosensory properties of EtOH and quinine was positively correlated in naïve rats, such that rats that were initially more accepting of quinine were also more accepting of EtOH. Rats that sampled quinine immediately prior to tasting EtOH exhibited successive positive contrast in that they were more accepting of highly concentrated EtOH, relative to a water-control group. Increased EtOH acceptance following exposure is, at least in part, facilitated by a decrease in its aversive sensory properties. Both long- and short-term access increase the palatability of the taste of EtOH in brief-access licking tests. Moreover, the sensitivity to the bitterness of quinine was predictive of acceptance of EtOH indicating some commonality in the sensory mechanisms that mediate the initial acceptance of the 2 stimuli. Accordingly, immediate prior exposure to quinine results in increased acceptance of EtOH, suggesting that successive positive contrast between oral stimuli may contribute to increased alcohol consumption. Copyright © 2017 by the Research Society on Alcoholism.
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Hinderliter, Charles F; Goodhart, Mark; Anderson, Matthew J; Misanin, James R
2002-06-01
Assuming body temperature correlates with metabolic activities, rate of body temperature recovery was manipulated to assess effects on long-trace conditioning in a conditioned taste-aversion paradigm. Following 10 min. access to a .1% saccharin solution and then 10 min. immersion in 0-0.5 degrees C water, two groups of 16 Wistar-derived, 81-113 day-old, male albino rats received either saline or lithium chloride injections 3 hr. later. These two groups were subdivided on basis of warming rate during the 3-hr. interval. Half of the rats recovered at room temperature (20 degrees to 21 degrees C), and half recovered in an incubator maintained at 30 degrees C. Maintaining a lowered body temperature between the conditioned stimulus and unconditioned stimulus allowed an association to be made at 3 hr., an interval that normally does not support conditioning. In contrast, lowering body temperature and then inducing a fast warming rate did not produce evidence of an aversion. It is suggested that maintaining a low body temperature over the interval between the presentation of the conditioned stimulus and unconditioned stimulus slows a metabolic clock that extends the measured interval at which associations can be made using conditioned taste-aversion procedures.
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Orosensory responsiveness to and preference for hydroxide-containing salts in mice.
St John, Steven J; Boughter, John D
2009-07-01
Historically, taste researchers have considered the possibility that the gustatory system detects basic compounds, such as those containing the hydroxide ion, but evidence for an "alkaline taste" has not been strong. We found that, in 48 h, 2-bottle preference tests, C3HeB/FeJ (C3) mice showed a preference for Ca(OH)(2), whereas SWR/J (SW) mice showed avoidance. Strain differences were also apparent to NaOH but not CaCl(2). Follow-up studies showed that the strain difference for Ca(OH)(2) was stable over time (Experiment 2) but that C3 and SW mice did not differ in their responses to Ca(OH)(2) or NaOH in brief-access tests, where both mice avoided high concentrations of these compounds (Experiment 3). In order to assess the perceived quality of Ca(OH)(2), mice were tested in 2 taste aversion generalization experiments (Experiments 4 and 5). Aversions to Ca(OH)(2) generalized to NaOH but not CaCl(2) in both strains, suggesting that the generalization was based on the hydroxide ion. Both strains also generalized aversions to quinine, suggesting the possibility that the hydroxide ion has a bitter taste quality to these mice, despite the preference shown by C3 mice to middle concentrations in long-term tests.
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Ross, Shani E; Lehmann Levin, Emily; Itoga, Christy A; Schoen, Chelsea B; Selmane, Romeissa; Aldridge, J Wayne
2016-10-01
We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever-pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self-stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory-excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an 'information lesion' that not only decreased motivational 'wanting' of food rewards, but also blocked 'liking' of rewards. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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Diaz-Granados, Jaime L; Graham, Danielle L
2007-12-01
Alcohol abuse among adolescents is prevalent. Epidemiological studies suggest that alcohol abuse during the adolescent developmental period may result in long-term changes such as an increased susceptibility to alcohol-related problems in adulthood. Laboratory findings suggest that alcohol exposure during the adolescent developmental period, as compared with adulthood, may differentially impact subsequent neurobehavioral responses to alcohol. The present study was designed to examine whether ethanol exposure, continuous versus intermittent, during the adolescent developmental period would alter the aversive properties of ethanol in adult C3H mice. Periadolescent (PD28) male C3H mice were exposed to 64 hours of continuous or intermittent ethanol vapor. As a comparison, adult (PD70) C3H mice were also exposed to 64 hours of continuous or intermittent ethanol vapor. Six weeks after ethanol exposure, taste aversion conditioning was carried out on both ethanol pre-exposed and ethanol-naive animals using a 1-trial, 1-flavor taste-conditioning procedure. Ethanol exposure during the periadolescent period significantly attenuated a subsequent ethanol-induced conditioned taste aversion, as compared with control animals. Adult animals exposed to chronic ethanol vapor during adolescence showed less of an aversion to an ethanol-paired flavor than ethanol-naive adults. Intermittent exposure to ethanol vapor during periadolescence produced a greater attenuation. It is suggested that ethanol exposure during the periadolescent period results in long-term neurobehavioral changes, which lessen a conditioned aversion to ethanol in adulthood. It is suggested that this age-related effect may underlie the increased susceptibility to alcohol-related problems which is negatively correlated with the age of onset for alcohol abuse.
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van den Bosch, I; van Delft, J M; de Wijk, R A; de Graaf, C; Boesveldt, S
2015-11-01
Evaluative conditioning may be an important mechanism for learning food preferences and aversions; however, in both real life and experimental settings it has not been consistently successful. The current study aimed to gain more insight into which underlying factors may contribute to a successful outcome of olfactory evaluative conditioning. Two groups of 18 participants came in on three consecutive days, and were repeatedly exposed to four novel, neutral odors (CS) coupled to varying disliked, neutral, liked, or no stimuli (taste and/or pictures, US), following a 50% reinforcement schedule, leading to 40 odor presentations per session. Liking ratings, as well as changes in the autonomic nervous system were assessed before, during and after conditioning. We were able to induce negative, but not positive, affective changes by pairing neutral odors with tastes and pictures differing in valence. Negative as well as multimodal stimuli appear to be more potent US, since they may be considered more salient. Lastly, results of the current study imply that heart rate is responsive to changes in valence of olfactory stimuli, and perhaps even more sensitive than explicit ratings of liking. Copyright © 2015 Elsevier Inc. All rights reserved.
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Role of the area postrema in three putative measures of motion sickness in the rat
NASA Technical Reports Server (NTRS)
Sutton, Richard L.; Fox, Robert A.; Daunton, Nancy G.
1991-01-01
After thermal cauterization of the area postrema in rats, the absence of conditioned taste aversion of sucrose paired with lithium chloride (0.15M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 deg/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.
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The molecular basis for attractive salt-taste coding in Drosophila.
Zhang, Yali V; Ni, Jinfei; Montell, Craig
2013-06-14
Below a certain level, table salt (NaCl) is beneficial for animals, whereas excessive salt is harmful. However, it remains unclear how low- and high-salt taste perceptions are differentially encoded. We identified a salt-taste coding mechanism in Drosophila melanogaster. Flies use distinct types of gustatory receptor neurons (GRNs) to respond to different concentrations of salt. We demonstrated that a member of the newly discovered ionotropic glutamate receptor (IR) family, IR76b, functioned in the detection of low salt and was a Na(+) channel. The loss of IR76b selectively impaired the attractive pathway, leaving salt-aversive GRNs unaffected. Consequently, low salt became aversive. Our work demonstrated that the opposing behavioral responses to low and high salt were determined largely by an elegant bimodal switch system operating in GRNs.
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Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C
2004-09-15
Rats repeatedly exposed to a distinctive novel solution (conditioned stimulus, CS) followed by the opportunity to run in a wheel subsequently drink less of this solution. Investigations on this phenomenon indicate that wheel running is an effective unconditioned stimulus (US) for establishing conditioned taste aversion (CTA) when using a forward conditioning procedure (i.e., the US-wheel running follows the CS-taste). However, other studies show that wheel running produces reliable preference for a distinctive place when pairings are backward (i.e., the CS-location follows the US-wheel running). One possibility to account for these results is that rewarding aftereffects of wheel running conditioned preference to the CS. The main objective of the present study was to assess the effects of backward conditioning using wheel running as the US and a distinctive taste as the CS. In a between-groups design, two experimental groups [i.e., forward (FC) and backward conditioning (BC)] and two control groups [CS-taste alone (TA) and CS-US unpaired (UNP)] were compared. Results from this experiment indicated that there is less suppression of drinking when a CS-taste followed a bout of wheel running. In fact, rats in the BC group drank more of the paired solution than all the other groups.
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Vasopressin and the Regulation of Thirst.
Bichet, Daniel G
2018-01-01
Recent experiments using optogenetic tools allow the identification and functional analysis of thirst neurons and vasopressin producing neurons. Two major advances provide a detailed anatomy of taste for water and arginine-vasopressin (AVP) release: (1) thirst and AVP release are regulated not only by the classical homeostatic, intero-sensory plasma osmolality negative feedback, but also by novel, extero-sensory, anticipatory signals. These anticipatory signals for thirst and vasopressin release converge on the same homeostatic neurons of circumventricular organs that monitor the composition of the blood; (2) acid-sensing taste receptor cells (which express polycystic kidney disease 2-like 1 protein) on the tongue that were previously suggested as the sour taste sensors also mediate taste responses to water. The tongue has a taste for water. The median preoptic nucleus (MnPO) of the hypothalamus could integrate multiple thirst-generating stimuli including cardiopulmonary signals, osmolality, angiotensin II, oropharyngeal and gastric signals, the latter possibly representing anticipatory signals. Dehydration is aversive and MnPO neuron activity is proportional to the intensity of this aversive state. © 2018 The Author(s) Published by S. Karger AG, Basel.
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Xiao, Xiao; Dupuis-Roy, Nicolas; Jiang, Jun; Du, Xue; Zhang, Mingmin; Zhang, Qinglin
2018-02-21
The functional magnetic resonance imaging (fMRI) technique was used to investigate brain activations related to conflict control in a taste-visual cross-modal pairing task. On each trial, participants had to decide whether the taste of a gustatory stimulus matched or did not match the expected taste of the food item depicted in an image. There were four conditions: Negative match (NM; sour gustatory stimulus and image of sour food), negative mismatch (NMM; sour gustatory stimulus and image of sweet food), positive match (PM; sweet gustatory stimulus and image of sweet food), positive mismatch (PMM; sweet gustatory stimulus and image of sour food). Blood oxygenation level-dependent (BOLD) contrasts between the NMM and the NM conditions revealed an increased activity in the middle frontal gyrus (MFG) (BA 6), the lingual gyrus (LG) (BA 18), and the postcentral gyrus. Furthermore, the NMM minus NM BOLD differences observed in the MFG were correlated with the NMM minus NM differences in response time. These activations were specifically associated with conflict control during the aversive gustatory stimulation. BOLD contrasts between the PMM and the PM condition revealed no significant positive activation, which supported the hypothesis that the human brain is especially sensitive to aversive stimuli. Altogether, these results suggest that the MFG is associated with the taste-visual cross-modal conflict control. A possible role of the LG as an information conflict detector at an early perceptual stage is further discussed, along with a possible involvement of the postcentral gyrus in the processing of the taste-visual cross-modal sensory contrast. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
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Moore, Eileen M.; Forrest, Robert D.; Boehm, Stephen L.
2012-01-01
Adolescent individuals display altered behavioral sensitivity to ethanol, which may contribute to the increased ethanol consumption seen in this age-group. However, genetics also exert considerable influence on both ethanol intake and sensitivity. Thus far there is little research assessing the combined influence of developmental and genetic alcohol sensitivities. Sensitivity to the aversive effects of ethanol using a conditioned taste aversion (CTA) procedure was measured during both adolescence (P30) and adulthood (P75) in 8 inbred mouse strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T+tf/J, C3H/HeJ, and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently provided with access to 0.9% (v/v) NaCl solution for 1h. Immediately following access mice were administered ethanol (0, 1.5, 2.25, 3g/kg, ip). This procedure was repeated in 72h intervals for a total of 5 CTA trials. Sensitivity to the aversive effects of ethanol was highly dependent upon both strain and age. Within an inbred strain, adolescent animals were consistently less sensitive to the aversive effects of ethanol than their adult counterparts. However, the dose of ethanol required to produce an aversion response differed as a function of both age and strain. PMID:23171343
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Murray, Elizabeth; Brouwer, Sietske; McCutcheon, Rob; Harmer, Catherine J; Cowen, Philip J; McCabe, Ciara
2014-11-01
Opioid antagonism reduces the consumption of palatable foods in humans but the neural substrates implicated in these effects are less well understood. The aim of the present study was to examine the effects of the opioid antagonist, naltrexone, on neural response to rewarding and aversive sight and taste stimuli. We used functional magnetic resonance imaging (fMRI) to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 20 healthy volunteers who received a single oral dose of naltrexone (50 mg) and placebo in a double-blind, repeated-measures cross-over, design. Relative to placebo, naltrexone decreased reward activation to chocolate in the dorsal anterior cingulate cortex and caudate, and increased aversive-related activation to unpleasant strawberry in the amygdala and anterior insula. These findings suggest that modulation of key brain areas involved in reward processing, cognitive control and habit formation such as the dorsal anterior cingulate cortex (dACC) and caudate might underlie reduction in food intake with opioid antagonism. Furthermore we show for the first time that naltrexone can increase activations related to aversive food stimuli. These results support further investigation of opioid treatments in obesity.
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Hiring a Gay Man, Taking a Risk?: A Lab Experiment on Employment Discrimination and Risk Aversion.
Baert, Stijn
2018-01-01
We investigate risk aversion as a driver of labor market discrimination against homosexual men. We show that more hiring discrimination by more risk-averse employers is consistent with taste-based and statistical discrimination. To test this hypothesis we conduct a scenario experiment in which experimental employers take a fictitious hiring decision concerning a heterosexual or homosexual male job candidate. In addition, participants are surveyed on their risk aversion and other characteristics that might correlate with this risk aversion. Analysis of the (post-)experimental data confirms our hypothesis. The likelihood of a beneficial hiring decision for homosexual male candidates decreases by 31.7% when employers are a standard deviation more risk-averse.
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Jahng, Jeong Won; Lee, Jong-Ho
2015-12-05
Intraperitoneal injections (ip) of lithium chloride at large doses induce c-Fos expression in the brain regions implicated in conditioned taste aversion (CTA) learning, and also activate the hypothalamic-pituitary-adrenal (HPA) axis and increase the plasma corticosterone levels in rats. A pharmacologic treatment blunting the lithium-induced c-Fos expression in the brain regions, but not the HPA axis activation, induced CTA formation. Synthetic glucocorticoids at conditioning, but not glucocorticoid antagonist, attenuated the lithium-induced CTA acquisition. The CTA acquisition by ip lithium was not affected by adrenalectomy regardless of basal corticosterone supplement, but the extinction was delayed in the absence of basal corticosterone. Glucocorticoids overloading delayed the extinction memory formation of lithium-induced CTA. ip lithium consistently induced the brain c-Fos expression, the HPA activation and CTA formation regardless of the circadian activation of the HPA axis. Intracerebroventricular (icv) injections of lithium at day time also increased the brain c-Fos expression, activated the HPA axis and induced CTA acquisition. However, icv lithium at night, when the HPA axis shows its circadian activation, did not induce CTA acquisition nor activate the HPA axis, although it increased the brain c-Fos expression. These results suggest that the circadian activation of the HPA axis may affect central, but not peripheral, effect of lithium in CTA learning in rats, and the HPA axis activation may be necessary for the central effect of lithium in CTA formation. Also, glucocorticoids may be required for a better extinction; however, increased glucocorticoids hinder both the acquisition and the extinction of lithium-induced CTA. Copyright © 2015. Published by Elsevier B.V.
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Second-Order Conditioning during a Compound Extinction Treatment
ERIC Educational Resources Information Center
Pineno, Oskar; Zilski, Jessica M.; Schachtman, Todd R.
2007-01-01
Two conditioned taste aversion experiments with rats were conducted to establish if a target taste that had received a prior pairing with illness could be subject to second-order conditioning during extinction treatment in compound with a flavor that also received prior conditioning. In these experiments, the occurrence of second-order…
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Investigating motion sickness using the conditioned taste aversion paradigm
NASA Technical Reports Server (NTRS)
Fox, Robert A.
1990-01-01
The use of conditioned taste aversion (CTA) to study motion sickness is reviewed. The use of CTA to measure motion sickness is supported by studies showing that an intact vestibular system is essential for the production of CTA when motion is the unconditioned stimulus. The magnitude of CTA is assessed at a time removed from exposure to motion, and therefore is not affected by residual effects of motion. Since the magnitude of CTA is assessed as volume or weight of flood or fluid, the degree of sickness is reflected in a continuous measure rather than in the discrete, all-or-none fashion characteristic of vomiting.
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De Brugada, Isabel; González, Felisa; Cándido, Antonio
2003-01-31
In one experiment using conditioned taste aversion and the unconditioned stimulus (US) preexposure procedure, one group of rats was given LiCl exposure for 3 days, whereas two other groups received saline. Following this phase, all groups were given a novel flavour (saccharine) to drink following either LiCl (group preexposed and one of the control groups) or saline injections (the remaining control group) and the consumption of the flavour was assessed. After this neophobia test, the acquired saccharine aversion was evaluated. The results show that three LiCl injections are enough to produce a US preexposure effect on backward excitatory taste aversion conditioning, whereas this number of injections procedure does not produce habituation of the increment in neophobia, an unconditioned response to the LiCl. The results are discussed taking into account different mechanisms involved in US preexposure effect.
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Moore, E M; Forrest, R D; Boehm, S L
2013-02-01
Adolescent individuals display altered behavioral sensitivity to ethanol, which may contribute to the increased ethanol consumption seen in this age-group. However, genetics also exert considerable influence on both ethanol intake and sensitivity. Currently there is little research assessing the combined influence of developmental and genetic alcohol sensitivities. Sensitivity to the aversive effects of ethanol using a conditioned taste aversion (CTA) procedure was measured during both adolescence (P30) and adulthood (P75) in eight inbred mouse strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T(+) tf/J, C3H/HeJ and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently provided with access to 0.9% (v/v) NaCl solution for 1 h. Immediately following access mice were administered ethanol (0, 1.5, 2.25 and 3 g/kg, ip). This procedure was repeated in 72 h intervals for a total of five CTA trials. Sensitivity to the aversive effects of ethanol was highly dependent upon both strain and age. Within an inbred strain, adolescent animals were consistently less sensitive to the aversive effects of ethanol than their adult counterparts. However, the dose of ethanol required to produce an aversion response differed as a function of both age and strain. © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
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Pautassi, Ricardo M; Nizhnikov, Michael E; Spear, Norman E
2009-06-01
The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects.
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Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.
2009-01-01
The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects. PMID:19428502
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Garcia-Burgos, David; Maglieri, Sabine; Vögele, Claus; Munsch, Simone
2018-01-01
Background: Despite on-going efforts to better understand dysregulated eating, the olfactory-gustatory deficits and food preferences in eating disorders (ED), and the mechanisms underlying the perception of and responses to food properties in anorexia nervosa (AN) and bulimia nervosa (BN) remain largely unknown; both during the course of the illness and compared to healthy populations. It is, therefore, necessary to systematically investigate the gustatory perception and hedonics of taste in patients with AN and BN. To this end, we will examine whether aversions to the taste of high-calorie food is related to the suppression of energy intake in restricting-type AN, and whether an increased hedonic valence of sweet, caloric-dense foods may be part of the mechanisms triggering binge-eating episodes in BN. In addition, the role of cognitions influencing these mechanisms will be examined. Method: In study 1, four mixtures of sweet-fat stimuli will be presented in a sensory two-alternative forced-choice test involving signal detection analysis. In study 2, a full-scale taste reactivity test will be carried out, including psychophysiological and behavioral measures to assess subtle and covert hedonic changes. We will compare the responses of currently-ill AN and BN patients to those who have recovered from AN and BN, and also to those of healthy normal-weight and underweight individuals without any eating disorder pathology. Discussion: If taste response profiles are differentially linked to ED types, then future studies should investigate whether taste responsiveness represents a useful diagnostic measure in the prevention, assessment and treatment of EDs. The expected results on cognitive mechanisms in the top-down processes of food hedonics will complement current models and contribute to the refinement of interventions to change cognitive aspects of taste aversions, to establish functional food preferences and to better manage food cravings associated with binge-eating episodes. No trial registration was required for this protocol, which was approved by the Swiss ethics committee (CER-VD, n° 2016-02150) and the Ethics Review Panel of the University of Luxembourg. PMID:29593595
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Garcia-Burgos, David; Maglieri, Sabine; Vögele, Claus; Munsch, Simone
2018-01-01
Background: Despite on-going efforts to better understand dysregulated eating, the olfactory-gustatory deficits and food preferences in eating disorders (ED), and the mechanisms underlying the perception of and responses to food properties in anorexia nervosa (AN) and bulimia nervosa (BN) remain largely unknown; both during the course of the illness and compared to healthy populations. It is, therefore, necessary to systematically investigate the gustatory perception and hedonics of taste in patients with AN and BN. To this end, we will examine whether aversions to the taste of high-calorie food is related to the suppression of energy intake in restricting-type AN, and whether an increased hedonic valence of sweet, caloric-dense foods may be part of the mechanisms triggering binge-eating episodes in BN. In addition, the role of cognitions influencing these mechanisms will be examined. Method: In study 1, four mixtures of sweet-fat stimuli will be presented in a sensory two-alternative forced-choice test involving signal detection analysis. In study 2, a full-scale taste reactivity test will be carried out, including psychophysiological and behavioral measures to assess subtle and covert hedonic changes. We will compare the responses of currently-ill AN and BN patients to those who have recovered from AN and BN, and also to those of healthy normal-weight and underweight individuals without any eating disorder pathology. Discussion: If taste response profiles are differentially linked to ED types, then future studies should investigate whether taste responsiveness represents a useful diagnostic measure in the prevention, assessment and treatment of EDs. The expected results on cognitive mechanisms in the top-down processes of food hedonics will complement current models and contribute to the refinement of interventions to change cognitive aspects of taste aversions, to establish functional food preferences and to better manage food cravings associated with binge-eating episodes. No trial registration was required for this protocol, which was approved by the Swiss ethics committee (CER-VD, n° 2016-02150) and the Ethics Review Panel of the University of Luxembourg.
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Bitter tastant responses in the amoeba Dictyostelium correlate with rat and human taste assays.
Cocorocchio, Marco; Ives, Robert; Clapham, David; Andrews, Paul L R; Williams, Robin S B
2016-01-01
Treatment compliance is reduced when pharmaceutical compounds have a bitter taste and this is particularly marked for paediatric medications. Identification of bitter taste liability during drug discovery utilises the rat in vivo brief access taste aversion (BATA) test which apart from animal use is time consuming with limited throughput. We investigated the suitability of using a simple, non-animal model, the amoeba Dictyostelium discoideum to investigate taste-related responses and particularly identification of compounds with a bitter taste liability. The effect of taste-related compounds on Dictyostelium behaviour following acute exposure (15 minutes) was monitored. Dictyostelium did not respond to salty, sour, umami or sweet tasting compounds, however, cells rapidly responded to bitter tastants. Using time-lapse photography and computer-generated quantification to monitor changes in cell membrane movement, we developed an assay to assess the response of Dictyostelium to a wide range of structurally diverse known bitter compounds and blinded compounds. Dictyostelium showed varying responses to the bitter tastants, with IC50 values providing a rank order of potency. Comparison of Dictyostelium IC50 values to those observed in response to a similar range of compounds in the rat in vivo brief access taste aversion test showed a significant (p = 0.0172) positive correlation between the two models, and additionally a similar response to that provided by a human sensory panel assessment test. These experiments demonstrate that Dictyostelium may provide a suitable model for early prediction of bitterness for novel tastants and drugs. Interestingly, a response to bitter tastants appears conserved from single-celled amoebae to humans.
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Sherrill, Luke K.; Berthold, Claire; Koss, Wendy A.; Juraska, Janice M.; Gulley, Joshua M.
2011-01-01
Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol s aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0 g/kg ethanol in a binge-like pattern during postnatal days (PD) 35–45. In adulthood (> PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5 g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. PMID:21767576
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Bitter or not? BitterPredict, a tool for predicting taste from chemical structure.
Dagan-Wiener, Ayana; Nissim, Ido; Ben Abu, Natalie; Borgonovo, Gigliola; Bassoli, Angela; Niv, Masha Y
2017-09-21
Bitter taste is an innately aversive taste modality that is considered to protect animals from consuming toxic compounds. Yet, bitterness is not always noxious and some bitter compounds have beneficial effects on health. Hundreds of bitter compounds were reported (and are accessible via the BitterDB http://bitterdb.agri.huji.ac.il/dbbitter.php ), but numerous additional bitter molecules are still unknown. The dramatic chemical diversity of bitterants makes bitterness prediction a difficult task. Here we present a machine learning classifier, BitterPredict, which predicts whether a compound is bitter or not, based on its chemical structure. BitterDB was used as the positive set, and non-bitter molecules were gathered from literature to create the negative set. Adaptive Boosting (AdaBoost), based on decision trees machine-learning algorithm was applied to molecules that were represented using physicochemical and ADME/Tox descriptors. BitterPredict correctly classifies over 80% of the compounds in the hold-out test set, and 70-90% of the compounds in three independent external sets and in sensory test validation, providing a quick and reliable tool for classifying large sets of compounds into bitter and non-bitter groups. BitterPredict suggests that about 40% of random molecules, and a large portion (66%) of clinical and experimental drugs, and of natural products (77%) are bitter.
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Cracking Taste Codes by Tapping into Sensory Neuron Impulse Traffic
Frank, Marion E.; Lundy, Robert F.; Contreras, Robert J.
2008-01-01
Insights into the biological basis for mammalian taste quality coding began with electrophysiological recordings from “taste” nerves and this technique continues to produce essential information today. Chorda tympani (geniculate ganglion) neurons, which are particularly involved in taste quality discrimination, are specialists or generalists. Specialists respond to stimuli characterized by a single taste quality as defined by behavioral cross-generalization in conditioned taste tests. Generalists respond to electrolytes that elicit multiple aversive qualities. Na+-salt (N) specialists in rodents and sweet-stimulus (S) specialists in multiple orders of mammals are well-characterized. Specialists are associated with species’ nutritional needs and their activation is known to be malleable by internal physiological conditions and contaminated external caloric sources. S specialists, associated with the heterodimeric G-protein coupled receptor: T1R, and N specialists, associated with the epithelial sodium channel: ENaC, are consistent with labeled line coding from taste bud to afferent neuron. Yet, S-specialist neurons and behavior are less specific thanT1R2-3 in encompassing glutamate and E generalist neurons are much less specific than a candidate, PDK TRP channel, sour receptor in encompassing salts and bitter stimuli. Specialist labeled lines for nutrients and generalist patterns for aversive electrolytes may be transmitting taste information to the brain side by side. However, specific roles of generalists in taste quality coding may be resolved by selecting stimuli and stimulus levels found in natural situations. T2Rs, participating in reflexes via the glossopharynygeal nerve, became highly diversified in mammalian phylogenesis as they evolved to deal with dangerous substances within specific environmental niches. Establishing the information afferent neurons traffic to the brain about natural taste stimuli imbedded in dynamic complex mixtures will ultimately “crack taste codes.” PMID:18824076
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Failure to produce taste-aversion learning in rats exposed to static electric fields and air ions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Creim, J.A.; Lovely, R.H.; Weigel, R.J.
1995-12-01
Taste-aversion (TA) learning was measured to determine whether exposure to high-voltage direct current (HVdc) static electric fields can produce TA learning in male Long Evans rats. Fifty-six rats were randomly distributed into four groups of 14 rats each. All rats were placed on a 20 min/day drinking schedule for 12 consecutive days prior to receiving five conditioning trials. During the conditioning trials, access to 0.1% sodium saccharin-flavored water was given for 20 min, followed 30 min later by one of four treatments. Two groups of 14 rats each were individually exposed to static electric fields and air ions, one groupmore » to +75 kV/m (+2 {times} 10{sup 5} air ions/cm{sup 3}) and the other group to {minus}75 kV/m ({minus}2 {times} 10{sup 5} air ions/cm{sup 3}). Two other groups of 14 rats each served as sham-exposed controls, with the following variation in one of the sham-exposed groups: this group was subdivided into two subsets of seven rats each, so that a positive control group could be included to validate the experimental design. The positive control group (n = 7) was injected with cyclophosphamide 25 mg/kg, i.p., 30 min after access to saccharin-flavored water on conditioning days, whereas the other subset of seven rats was similarly injected with an equivalent volume of saline. Access to saccharin-flavored water on conditioning days was followed by the treatments described above and was alternated daily with water recovery sessions in which the rats received access to water for 20 min in the home cage without further treatment. Following the last water-recovery session, a 20 min, two-bottle preference test (between water and saccharin-flavored water) was administered to each group. The positive control group did show TA learning, thus validating the experimental protocol.« less
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Conditioned taste aversion to ethanol in a social context: impact of age and sex.
Morales, Melissa; Schatz, Kelcie C; Anderson, Rachel I; Spear, Linda P; Varlinskaya, Elena I
2014-03-15
Given that human adolescents place a high value on social interactions-particularly while consuming alcohol-the current study utilized a novel social drinking paradigm to examine rewarding and aversive properties of ethanol in non-water deprived rats that were housed and tested in groups of five same-sex littermates. On postnatal day P34 (adolescents) or P69 (adults), rats were habituated to the testing apparatus for 30 min. On the next day, animals were placed into the test apparatus and given 30 min access to a supersaccharin solution (3% sucrose; 0.125% saccharin), followed immediately by an intraperitoneal injection of ethanol (0, 0.25, 0.5, 1.0, 1.5 g/kg). Subsequent intake of the supersacharrin solution was assessed on three consecutive test days. Adolescent males were less sensitive to ethanol's aversive effects than adult males, with adolescent males maintaining an aversion on all three test days only at the 1.5 g/kg dose, whereas adults demonstrated aversions across test days to 1 and 1.5 g/kg. Adolescent females maintained aversions to 1 and 1.5 g/kg across days, whereas adult females continued to show an aversion to the 1.5 g/kg dose only. These opposite patterns of sensitivity that emerged among males and females at each age in the propensity to maintain an ethanol-induced taste aversion under social conditions may contribute to age- and sex-related differences in ethanol intake. Testing in social groups may be useful for future work when studying rodent models of adolescent alcohol use given the importance that human adolescents place on drinking in social settings. Copyright © 2014 Elsevier B.V. All rights reserved.
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Schramm-Sapyta, Nicole L; DiFeliceantonio, Alexandra G; Foscue, Ethan; Glowacz, Susan; Haseeb, Naadeyah; Wang, Nancy; Zhou, Cathy; Kuhn, Cynthia M
2010-12-01
Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol's physiologic effects? Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs). We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs. These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol. Copyright © 2010 by the Research Society on Alcoholism.
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Wakeford, Alison G P; Flax, Shaun M; Pomfrey, Rebecca L; Riley, Anthony L
2016-01-01
Adolescent initiation of drug use has been linked to problematic drug taking later in life and may represent an important variable that changes the balance of the rewarding and/or aversive effects of abused drugs which may contribute to abuse vulnerability. The current study examined the effects of adolescent THC exposure on THC-induced place preference (rewarding effects) and taste avoidance (aversive effects) conditioning in adulthood. Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC (3.2mg/kg) or vehicle. After these injections, animals were allowed to mature and then trained in a combined CTA/CPP procedure in adulthood (PND ~90). Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test. THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure. Adolescent exposure to THC had no effect on THC taste and place conditioning in adulthood. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.
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ERIC Educational Resources Information Center
Garcia-DeLaTorre, Paola; Rodriguez-Ortiz, Carlos J.; Arreguin-Martinez, Jose L.; Cruz-Castaneda, Paulina; Bermudez-Rattoni, Federico
2009-01-01
Reconsolidation has been described as a process where a consolidated memory returns to a labile state when retrieved. Growing evidence suggests that reconsolidation is, in fact, a destabilization/stabilization process that incorporates updated information to a previously consolidated memory. We used the conditioned taste aversion (CTA) task in…
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Mickley, G. Andrew; Ketchesin, Kyle D.; Ramos, Linnet; Luchsinger, Joseph R.; Rogers, Morgan M.; Wiles, Nathanael R.; Hoxha, Nita
2012-01-01
Due to its relevance to clinical practice, extinction of learned fears has been a major focus of recent research. However, less is known about the means by which conditioned fears re-emerge (i.e., spontaneously recover) as time passes or contexts change following extinction. The periaqueductal gray represents the final common pathway mediating defensive reactions to fear and we have reported previously that the dorsolateral PAG (dlPAG) exhibits a small but reliable increase in neural activity (as measured by c-fos protein immunoreactivity) when spontaneous recovery (SR) of a conditioned taste aversion (CTA) is reduced. Here we extend these correlational studies to determine if inducing dlPAG c-fos expression through electrical brain stimulation could cause a reduction in SR of a CTA. Male Sprague-Dawley rats acquired a strong aversion to saccharin (conditioned stimulus; CS) and then underwent CTA extinction through multiple non-reinforced exposures to the CS. Following a 30-day latency period after asymptotic extinction was achieved; rats either received stimulation of the dorsal PAG (dPAG) or stimulation of closely adjacent structures. Sixty minutes following the stimulation, rats were again presented with the saccharin solution as we tested for SR of the CTA. The brain stimulation evoked c-fos expression around the tip of the electrodes. However, stimulation of the dPAG failed to reduce SR of the previously extinguished CTA. In fact, dPAG stimulation caused rats to significantly suppress their saccharin drinking (relative to controls) – indicating an enhanced SR. These data refute a cause-and-effect relationship between enhanced dPAG c-fos expression and a reduction in SR. However, they highlight a role for the dPAG in modulating SR of extinguished CTAs. PMID:23183042
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Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.
Schramm-Sapyta, Nicole L; Francis, Reynold; MacDonald, Andrea; Keistler, Colby; O'Neill, Lauren; Kuhn, Cynthia M
2014-04-01
Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse. This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development. Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats. CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns. These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.
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Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M
2011-11-20
Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. Copyright © 2011 Elsevier B.V. All rights reserved.
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Mantella, Nicole M; Youngentob, Steven L
2014-01-01
Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our results suggest broader implications related to the consequence of fetal exposure with one substance of abuse and initial acceptability of others.
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Mantella, Nicole M.; Youngentob, Steven L.
2014-01-01
Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our results suggest broader implications related to the consequence of fetal exposure with one substance of abuse and initial acceptability of others. PMID:25029285
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Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.
Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L
2016-01-15
Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace. Copyright © 2015 Elsevier B.V. All rights reserved.
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NASA Technical Reports Server (NTRS)
Fox, Robert A.; Sutton, R. L.; Mckenna, Susan
1991-01-01
Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.
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Makaronidis, Janine M; Neilson, Sabrina; Cheung, Wui-Hang; Tymoszuk, Urszula; Pucci, Andrea; Finer, Nicholas; Doyle, Jacqueline; Hashemi, Majid; Elkalaawy, Mohamed; Adamo, Marco; Jenkinson, Andrew; Batterham, Rachel L
2016-12-01
Reduced energy intake drives weight loss following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures. Post-operative changes in subjective appetite, taste, and smell and food preferences are reported and suggested to contribute to reduced energy intake. We aimed to investigate the prevalence of these changes following RYGB and SG and to evaluate their relationship with weight loss. 98 patients post-RYGB and 155 post-SG from a single bariatric centre were recruited to a cross-sectional study. Participants completed a questionnaire, previously utilised in post-operative bariatric patients, to assess the prevalence of post-operative food aversions and subjective changes in appetite, taste and smell. Anthropometric data were collected and percentage weight loss (%WL) was calculated. The relationship between food aversions, changes in appetite, taste and smell and %WL was assessed. The influence of time post-surgery, gender and type 2 diabetes (T2D) were evaluated. Following RYGB and SG the majority of patients reported food aversions (RYGB = 62%, SG = 59%), appetite changes (RYGB = 91%, SG = 91%) and taste changes (RYGB = 64%, SG = 59%). Smell changes were more common post-RYGB than post-SG (RYGB = 41%, SG = 28%, p = 0.039). No temporal effect was observed post-RYGB. In contrast, the prevalence of appetite changes decreased significantly with time following SG. Post-operative appetite changes associated with and predicted higher %WL post-SG but not post-RYGB. Taste changes associated with and predicted higher %WL following RYGB but not post-SG. There was no gender effect post-RYGB. Post-SG taste changes were less common in males (female = 65%, males = 40%, p = 0.008). T2D status in females did not influence post-operative subjective changes. However, in males with T2D, taste changes were less common post-SG than post-RYGB together with lower %WL (RYGB = 27.5 ± 2.7, SG = 14.6 ± 2.1, p = 0.003). Further research is warranted to define the biology underlying these differences and to individualise treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Neural processing of reward and punishment in young people at increased familial risk of depression.
McCabe, Ciara; Woffindale, Caroline; Harmer, Catherine J; Cowen, Philip J
2012-10-01
Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16-21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Conditioned taste avoidance induced by forced and voluntary wheel running in rats.
Forristall, J R; Hookey, B L; Grant, V L
2007-03-01
Voluntary exercise by rats running in a freely rotating wheel (free wheel) produces conditioned taste avoidance (CTA) of a flavored solution consumed before running [e.g., Lett, B.T., Grant, V.L., 1996. Wheel running induces conditioned taste aversion in rats trained while hungry and thirsty. Physiol. Behav. 59, 699-702]. Forced exercise, swimming or running, also produces CTA in rats [e.g., Masaki, T., Nakajima, S., 2006. Taste aversion induced by forced swimming, voluntary running, forced running, and lithium chloride injection treatments. Physiol. Behav. 88, 411-416]. Energy expenditure may be the critical factor in producing such CTA. If so, forced running in a motorized running wheel should produce CTA equivalent to that produced by a similar amount of voluntary running. In two experiments, we compared forced running in a motorized wheel with voluntary running in a free wheel. Mean distance run over 30 min was equated as closely as possible in the two apparatuses. Both types of exercise produced CTA relative to sedentary, locked-wheel controls. However, voluntary running produced greater CTA than forced running. We consider differences between running in the free and motorized wheels that may account for the differences in strength of CTA.
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CREB regulates memory allocation in the insular cortex
Sano, Yoshitake; Shobe, Justin L.; Zhou, Miou; Huang, Shan; Shuman, Tristan; Cai, Denise J.; Golshani, Peyman; Kamata, Masakazu; Silva, Alcino J.
2016-01-01
Summary The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory [1, 2]. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cAMP response element binding protein (CREB) are more likely to be recruited into encoding and storing fear memory [3–6]. To determine whether specific mechanisms also regulate memory allocation in other brain regions, and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (CS) with the experience of malaise (such as that induced by LiCl; US). The insular cortex is required for CTA memory formation and retrieval [7–12]. CTA learning activates a subpopulation of neurons in this structure [13–15], and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation [16, 17]. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc Fluorescence In Situ Hybridization (FISH) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory. PMID:25454591
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O'Tousa, David S; Grahame, Nicholas J
2016-07-01
Negative outcomes of alcoholism are progressively more severe as the duration of problem of alcohol use increases. Additionally, alcoholics demonstrate tendencies to neglect negative consequences associated with drinking and/or to choose to drink in the immediate presence of warning factors against drinking. The recently derived crossed high-alcohol-preferring (cHAP) mice, which volitionally drink to heavier intoxication (as assessed by blood ethanol [EtOH] concentration) than other alcohol-preferring populations, as well as spontaneously escalating their intake, may be a candidate to explore mechanisms underlying long-term excessive drinking. Here, we hypothesized that an extended drinking history would reduce the ability of 2 manipulations (forced abstinence [FA] and conditioned taste aversion [CTA]) to attenuate drinking. Experiment 1 examined differences between groups drinking for either 14 or 35 days, half of each subjected to 7 days of FA and half not, to characterize the potential changes in postabstinence drinking resulting from an extended drinking history. Experiment 2 used a CTA procedure to assess stimulus specificity of the ability of an aversive flavorant to decrease alcohol consumption. Experiment 3 used this taste aversion procedure to assess differences among groups drinking for 1, 14, or 35 days in their propensity to overcome this aversion when the flavorant was mixed with either EtOH or water. Experiment 1 demonstrated that although FA decreased alcohol consumption in mice with a 14-day drinking history, it failed to do so in mice drinking alcohol for 35 days. Experiment 2 showed that the addition of a flavorant only suppressed alcohol drinking if an aversion to the flavorant was previously established. Experiment 3 demonstrated that an extended drinking history expedited extinction of suppressed alcohol intake caused by a conditioned aversive flavor. These data show that a history of long-term drinking in cHAP mice attenuates the efficacy of interventions that normally reduce drinking. Analogous to alcoholics who may encounter difficulties in limiting their intake, cHAP mice with long drinking histories are relatively insensitive to both abstinence and signals of harmful consequences. We propose that the cHAP line may be a valid model for adaptations that occur following the extended heavy alcohol drinking. Copyright © 2016 by the Research Society on Alcoholism.
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Orosensory Responsiveness to and Preference for Hydroxide-Containing Salts in Mice
St. John, Steven J.; Boughter, John D.
2009-01-01
Historically, taste researchers have considered the possibility that the gustatory system detects basic compounds, such as those containing the hydroxide ion, but evidence for an “alkaline taste” has not been strong. We found that, in 48 h, 2-bottle preference tests, C3HeB/FeJ (C3) mice showed a preference for Ca(OH)2, whereas SWR/J (SW) mice showed avoidance. Strain differences were also apparent to NaOH but not CaCl2. Follow-up studies showed that the strain difference for Ca(OH)2 was stable over time (Experiment 2) but that C3 and SW mice did not differ in their responses to Ca(OH)2 or NaOH in brief-access tests, where both mice avoided high concentrations of these compounds (Experiment 3). In order to assess the perceived quality of Ca(OH)2, mice were tested in 2 taste aversion generalization experiments (Experiments 4 and 5). Aversions to Ca(OH)2 generalized to NaOH but not CaCl2 in both strains, suggesting that the generalization was based on the hydroxide ion. Both strains also generalized aversions to quinine, suggesting the possibility that the hydroxide ion has a bitter taste quality to these mice, despite the preference shown by C3 mice to middle concentrations in long-term tests. PMID:19423656
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Salty taste deficits in CALHM1 knockout mice.
Tordoff, Michael G; Ellis, Hillary T; Aleman, Tiffany R; Downing, Arnelle; Marambaud, Philippe; Foskett, J Kevin; Dana, Rachel M; McCaughey, Stuart A
2014-07-01
Genetic ablation of calcium homeostasis modulator 1 (CALHM1), which releases adenosine triphosphate from Type 2 taste cells, severely compromises the behavioral and electrophysiological responses to tastes detected by G protein-coupled receptors, such as sweet and bitter. However, the contribution of CALHM1 to salty taste perception is less clear. Here, we evaluated several salty taste-related phenotypes of CALHM1 knockout (KO) mice and their wild-type (WT) controls: 1) In a conditioned aversion test, CALHM1 WT and KO mice had similar NaCl avoidance thresholds. 2) In two-bottle choice tests, CALHM1 WT mice showed the classic inverted U-shaped NaCl concentration-preference function but CALHM1 KO mice had a blunted peak response. 3) In brief-access tests, CALHM1 KO mice showed less avoidance than did WT mice of high concentrations of NaCl, KCl, NH(4)Cl, and sodium lactate (NaLac). Amiloride further ameliorated the NaCl avoidance of CALHM1 KO mice, so that lick rates to a mixture of 1000 mM NaCl + 10 µM amiloride were statistically indistinguishable from those to water. 4) Relative to WT mice, CALHM1 KO mice had reduced chorda tympani nerve activity elicited by oral application of NaCl, NaLac, and sucrose but normal responses to HCl and NH(4)Cl. Chorda tympani responses to NaCl and NaLac were amiloride sensitive in WT but not KO mice. These results reinforce others demonstrating that multiple transduction pathways make complex, concentration-dependent contributions to salty taste perception. One of these pathways depends on CALHM1 to detect hypertonic NaCl in the mouth and signal the aversive taste of concentrated salt. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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French, Alice; Ali Agha, Moutaz; Mitra, Aniruddha; Yanagawa, Aya; Sellier, Marie-Jeanne; Marion-Poll, Frédéric
2015-01-01
Most animals possess taste receptors neurons detecting potentially noxious compounds. In humans, the ligands which activate these neurons define a sensory space called “bitter”. By extension, this term has been used in animals and insects to define molecules which induce aversive responses. In this review, based on our observations carried out in Drosophila, we examine how bitter compounds are detected and if bitter-sensitive neurons respond only to molecules bitter to humans. Like most animals, flies detect bitter chemicals through a specific population of taste neurons, distinct from those responding to sugars or to other modalities. Activating bitter-sensitive taste neurons induces aversive reactions and inhibits feeding. Bitter molecules also contribute to the suppression of sugar-neuron responses and can lead to a complete inhibition of the responses to sugar at the periphery. Since some bitter molecules activate bitter-sensitive neurons and some inhibit sugar detection, bitter molecules are represented by two sensory spaces which are only partially congruent. In addition to molecules which impact feeding, we recently discovered that the activation of bitter-sensitive neurons also induces grooming. Bitter-sensitive neurons of the wings and of the legs can sense chemicals from the gram negative bacteria, Escherichia coli, thus adding another biological function to these receptors. Bitter-sensitive neurons of the proboscis also respond to the inhibitory pheromone, 7-tricosene. Activating these neurons by bitter molecules in the context of sexual encounter inhibits courting and sexual reproduction, while activating these neurons with 7-tricosene in a feeding context will inhibit feeding. The picture that emerges from these observations is that the taste system is composed of detectors which monitor different “categories” of ligands, which facilitate or inhibit behaviors depending on the context (feeding, sexual reproduction, hygienic behavior), thus considerably extending the initial definition of “bitter” tasting. PMID:26635553
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PERCEPTION OF SWEET TASTE IS IMPORTANT FOR VOLUNTARY ALCOHOL CONSUMPTION IN MICE
Blednov, Y.A.; Walker, D.; Martinez, M.; Levine, M.; Damak, S.; Margolskee, R.F.
2012-01-01
To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: α-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild type mice, whereas Tas1r3 null mice were not different from wild-type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in conditioned taste aversion to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol. PMID:17376151
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Learning the specific quality of taste reinforcement in larval Drosophila.
Schleyer, Michael; Miura, Daisuke; Tanimura, Teiichi; Gerber, Bertram
2015-01-27
The only property of reinforcement insects are commonly thought to learn about is its value. We show that larval Drosophila not only remember the value of reinforcement (How much?), but also its quality (What?). This is demonstrated both within the appetitive domain by using sugar vs amino acid as different reward qualities, and within the aversive domain by using bitter vs high-concentration salt as different qualities of punishment. From the available literature, such nuanced memories for the quality of reinforcement are unexpected and pose a challenge to present models of how insect memory is organized. Given that animals as simple as larval Drosophila, endowed with but 10,000 neurons, operate with both reinforcement value and quality, we suggest that both are fundamental aspects of mnemonic processing-in any brain.
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Woloshchuk, Claudia J; Nelson, Katharine H; Rice, Kenner C; Riley, Anthony L
2016-10-01
Drug use is thought to be a balance of the rewarding and aversive effects of drugs. Understanding how various factors impact these properties and their relative balance may provide insight into their abuse potential. In this context, the present study attempted to evaluate the effects of drug history on the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV), one of a variety of synthetic cathinones (collectively known as "bath salts"). Different groups of male Sprague-Dawley rats were exposed to either vehicle or MDPV (1.8mg/kg) once every fourth day for five total injections prior to taste avoidance conditioning in which a novel saccharin solution was repeatedly paired with either vehicle, MDPV (1.8mg/kg), the related psychostimulant cocaine (18mg/kg) or the emetic lithium chloride (LiCl) (13.65mg/kg). In animals pre-exposed to vehicle, all three drugs induced significant and comparable taste avoidance relative to animals injected with vehicle during conditioning. MDPV pre-exposure attenuated the avoidance induced by both MDPV and cocaine (greater attenuation for MDPV than cocaine), but had no effect on that induced by LiCl. These findings suggest that a history of MDPV use may reduce or attenuate MDPV and cocaine's (but not LiCl's) aversive effects. The implications for such changes in MDPV's aversive effects to its potential use and abuse were discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Acevedo, María Belén; Nizhnikov, Michael E; Spear, Norman E; Molina, Juan C; Pautassi, Ricardo M
2013-05-01
Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol's motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference (CPP) by ethanol at this age. The present study assessed age-related differences in ethanol's motor stimulating effects and analyzed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced CPP and conditioned taste aversion (CTA) in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol's aversive reinforcement, but they also exhibited CPP. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA. Copyright © 2012 Wiley Periodicals, Inc.
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Acevedo, María Belén; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.; Pautassi, Ricardo Marcos
2012-01-01
Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol’s motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference by ethanol at this age. The present study assessed age-related differences in ethanol’s motor stimulating effects and analysed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced conditioned place preference and conditioned taste aversion in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol’s aversive reinforcement, but they also exhibited conditioned place preference. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA. PMID:22592597
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Morales, Melissa; Spear, Linda P
2013-03-01
We have previously demonstrated that gonadectomy either prior to (early) or after (late) puberty elevated ethanol consumption in males to levels similar to intact adult females-effects that were attenuated by testosterone replacement. To assess whether alterations in the aversive effects of ethanol might contribute to gonadectomy-associated increases in ethanol intake in males, the present study examined the impact of gonadectomy on conditioned taste aversions (CTA) to ethanol in male and female Sprague-Dawley rats. Animals were gonadectomized, received sham surgery (SH) or non-manipulated (NM) on postnatal (P) day 23 (early) or 67 (late) and tested for CTA to ethanol in adulthood. Water-deprived rats were given 1 hr access every-other-day to 10% sucrose followed by an injection of ethanol (0, 1g/kg) for 5 test sessions. Test data were analyzed to determine the first day significant aversions emerged in each ethanol group (i.e., sucrose intakes significantly less than their saline-injected counterparts). Early gonadectomized males acquired the CTA more rapidly than did early SH and NM males (day 1 vs 3 and 4 respectively), whereas a gonadectomy-associated enhancement in ethanol CTA was not evident in late males. Among females, gonadectomy had little impact on ethanol-induced CTA, with females in all groups showing an aversion by the first or second day, regardless of surgery age. These data suggest that previously observed elevations in ethanol intake induced by either pre- or post-pubertal gonadectomy in males are not related simply to gonadectomy-induced alterations in the aversive effects of ethanol indexed via CTA. Copyright © 2012 Elsevier B.V. All rights reserved.
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Effect of low body temperature on associative interference in conditioned taste aversion.
Christianson, John P; Anderson, Mathew J; Misanin, James R; Hinderliter, Charles F
2005-06-01
When two novel conditioned stimuli precede an unconditioned stimulus (US), the interval between the two conditioned stimuli (CS1 and CS2) influences the magnitude of the CS-US associability of each CS. As the interval between CS1 and CS2 increases, the associability of CS1 with the US decreases due to interference by CS2 and the associability of CS2 increases, given its temporal proximity to the US. Because hypothermia has been reported to increase the interval at which conditioned taste aversions can be formed, its influence was examined on the above relationship, i.e., how interference from CS2 affects the associability of CS1 with the US. Rats received a conditioned taste aversion procedure where CS1 and CS2 were presented either one after the other or separated by an 80-min. delay. For all subjects, the US or pseudo-US was presented immediately after CS2. When hypothermia was interpolated between the two flavor stimuli that were spaced 80 min. apart, CS2-interference with the CS1-US association was greatly attenuated. We propose that hypothermia modifies internal timing mechanisms such that the externally timed 80-min. CS1-CS2 interval was perceived as much shorter for rats made hypothermic. As a result of this perceived shortened inter-CS interval, CS2 produced less interference for the CS1-US association than would be expected for such a relatively long delay between CS1 and CS2.
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Role of acetaldehyde in ethanol-induced conditioned taste aversion in rats.
Escarabajal, M Dolores; De Witte, Philippe; Quertemont, Etienne
2003-05-01
In spite of many recent studies on the effects of acetaldehyde, it is still unclear whether acetaldehyde mediates the reinforcing and/or aversive effects of ethanol. The present study reexamined the role of acetaldehyde in ethanol-induced conditioned taste aversion (CTA). A first experiment compared ethanol- and acetaldehyde-induced CTA. In a second experiment, cyanamide, an aldehyde dehydrogenase inhibitor, was administered before conditioning with either ethanol or acetaldehyde to investigate the effects of acetaldehyde accumulation. A classic CTA protocol was used to associate the taste of a saccharin solution with either ethanol or acetaldehyde injections. In experiment 1, saccharin consumption was followed by injections of either ethanol (0, 0.5, 1.0, 1.5 or 2.0 g/kg) or acetaldehyde (0, 100, 170 or 300 mg/kg). In experiment 2, the rats were pretreated with either saline or cyanamide (25 mg/kg) before conditioning with either ethanol or acetaldehyde. Both ethanol and acetaldehyde induced significant CTA. However, ethanol produced a very strong CTA relative to acetaldehyde that induced only a weak CTA even at toxic doses. Cyanamide pretreatments significantly potentiated ethanol- but not acetaldehyde-induced CTA. The present results indicate that ethanol-induced CTA does not result from brain acetaldehyde effects. In contrast, it is suggested that the reinforcing effects of brain acetaldehyde might actually reduce ethanol-induced CTA. Our results also suggest that the inhibition of brain catalase activity may contribute to the potentiating effects of cyanamide on ethanol-induced CTA.
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Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal “bitter taste” cue
Davidson, Terry L.; Powley, Terry L.
2011-01-01
The discovery that cells in the gastrointestinal (GI) tract express the same molecular receptors and intracellular signaling components known to be involved in taste has generated great interest in potential functions of such post-oral “taste” receptors in the control of food intake. To determine whether taste cues in the GI tract are detected and can directly influence behavior, the present study used a microbehavioral analysis of intake, in which rats drank from lickometers that were programmed to simultaneously deliver a brief yoked infusion of a taste stimulus to the intestines. Specifically, in daily 30-min sessions, thirsty rats with indwelling intraduodenal catheters were trained to drink hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M NaCl solution. Once trained, in a subsequent series of intestinal taste probe trials, rats reduced licking during a 6-min infusion period, when a bitter stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for infusion, apparently conditioning a mild taste aversion. Presentation of the DB in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the development of the response across trials and strengthened the temporal resolution of the early licking suppression in response to the arrival of the DB in the intestine. In an experiment to evaluate whether CCK is involved as a paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist devazepide partially blocked the response to intestinal DB. In contrast to their ability to detect and avoid the bitter taste in the intestine, rats did not modify their licking to saccharin intraduodenal probe infusions. The intestinal taste aversion paradigm developed here provides a sensitive and effective protocol for evaluating which tastants—and concentrations of tastants—in the lumen of the gut can control ingestion. PMID:21865540
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Failure to produce taste-aversion learning in rats exposed to static electric fields and air ions.
Creim, J A; Lovely, R H; Weigel, R J; Forsythe, W C; Anderson, L E
1995-01-01
Taste-aversion (TA) learning was measured to determine whether exposure to high-voltage direct current (HVdc) static electric fields can produce TA learning in male Long Evans rats. Fifty-six rats were randomly distributed into four groups of 14 rats each. All rats were placed on a 20 min/day drinking schedule for 12 consecutive days prior to receiving five conditioning trials. During the conditioning trials, access to 0.1% sodium saccharin-flavored water was given for 20 min, followed 30 min later by one of four treatments. Two groups of 14 rats each were individually exposed to static electric fields and air ions, one group to +75 kV/m (+2 x 10(5) air ions/cm3) and the other group to -75 kV/m (-2 x 10(5) air ions/cm3). Two other groups of 14 rats each served as sham-exposed controls, with the following variation in one of the sham-exposed groups: This group was subdivided into two subsets of seven rats each, so that a positive control group could be included to validate the experimental design. The positive control group (n = 7) was injected with cyclophosphamide 25 mg/kg, i.p., 30 min after access to saccharin-flavored water on conditioning days, whereas the other subset of seven rats was similarly injected with an equivalent volume of saline. Access to saccharin-flavored water on conditioning days was followed by the treatments described above and was alternated daily with water "recovery" sessions in which the rats received access to water for 20 min in the home cage without further treatment. Following the last water-recovery session, a 20 min, two-bottle preference test (between water and saccharin-flavored water) was administered to each group. The positive control group did show TA learning, thus validating the experimental protocol. No saccharin-flavored water was consumed in the two-bottle preference test by the cyclophosphamide-injected, sham-exposed group compared to 74% consumed by the saline-injected sham-exposed controls (P < .0001). Saccharin-preference data for the static field-exposed groups showed no TA learning compared to data for sham-exposed controls. In summary, exposure to intense static electric fields and air ions did not produce TA learning as assessed by this particular design.
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Hempel, Briana J; Wakeford, Alison G P; Clasen, Matthew M; Friar, Mary A; Riley, Anthony L
2016-05-01
In pre-clinical models of marijuana abuse, there is relatively limited evidence of delta-9-tetrahydrocannabinol's (THC) rewarding effects, as indexed by its general inability to induce a place preference. One explanation for this failure is that its rewarding effects are masked by its concurrently occurring aversive properties. Consistent with this explanation, THC pre-exposure, which presumably weakens its aversive effects, induces place preferences. Such demonstrations are limited to mice and given reported species differences in THC reactivity, it is unknown to what extent the same shift in affective properties would be evident in rats. The present experiment examined the effect of THC history (3.2mg/kg) on THC (1 or 3.2mg/kg) induced place preference conditioning in rats. An assessment of taste avoidance was also run to independently characterize THC's aversive effects and any changes that occurred with drug pre-exposure. These assessments were made in a combined taste avoidance/place preference procedure in which a novel saccharin solution and environment were paired with THC (0, 1 or 3.2mg/kg). THC did not induce place conditioning, and a history of THC was ineffective in increasing THC's ability to do so, despite the fact that this same history significantly attenuated the aversive effects of THC. The failure of THC to consistently induce place preferences has been argued to be a function of its concurrently occurring aversive effects masking its rewarding properties. The fact that pre-exposure to THC significantly reduced its aversive effects without impacting THC's ability to induce place preferences suggests that THC has weak rewarding effects and/or its residual aversive affects may have still masked its rewarding properties. An important area for future work will be characterizing under what conditions THC is rewarding and whether its overall reinforcing effects are impacted by the relationship between its affective properties. Copyright © 2016 Elsevier Inc. All rights reserved.
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Salty Taste Deficits in CALHM1 Knockout Mice
Ellis, Hillary T.; Aleman, Tiffany R.; Downing, Arnelle; Marambaud, Philippe; Foskett, J. Kevin; Dana, Rachel M.; McCaughey, Stuart A.
2014-01-01
Genetic ablation of calcium homeostasis modulator 1 (CALHM1), which releases adenosine triphosphate from Type 2 taste cells, severely compromises the behavioral and electrophysiological responses to tastes detected by G protein–coupled receptors, such as sweet and bitter. However, the contribution of CALHM1 to salty taste perception is less clear. Here, we evaluated several salty taste–related phenotypes of CALHM1 knockout (KO) mice and their wild-type (WT) controls: 1) In a conditioned aversion test, CALHM1 WT and KO mice had similar NaCl avoidance thresholds. 2) In two-bottle choice tests, CALHM1 WT mice showed the classic inverted U-shaped NaCl concentration-preference function but CALHM1 KO mice had a blunted peak response. 3) In brief-access tests, CALHM1 KO mice showed less avoidance than did WT mice of high concentrations of NaCl, KCl, NH4Cl, and sodium lactate (NaLac). Amiloride further ameliorated the NaCl avoidance of CALHM1 KO mice, so that lick rates to a mixture of 1000mM NaCl + 10 µM amiloride were statistically indistinguishable from those to water. 4) Relative to WT mice, CALHM1 KO mice had reduced chorda tympani nerve activity elicited by oral application of NaCl, NaLac, and sucrose but normal responses to HCl and NH4Cl. Chorda tympani responses to NaCl and NaLac were amiloride sensitive in WT but not KO mice. These results reinforce others demonstrating that multiple transduction pathways make complex, concentration-dependent contributions to salty taste perception. One of these pathways depends on CALHM1 to detect hypertonic NaCl in the mouth and signal the aversive taste of concentrated salt. PMID:24846212
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Consumption of an acute dose of caffeine reduces acquisition but not memory in the honey bee.
Mustard, Julie A; Dews, Lauren; Brugato, Arlana; Dey, Kevin; Wright, Geraldine A
2012-06-15
Caffeine affects several molecules that are also involved in the processes underlying learning and memory such as cAMP and calcium. However, studies of caffeine's influence on learning and memory in mammals are often contradictory. Invertebrate model systems have provided valuable insight into the actions of many neuroactive compounds including ethanol and cocaine. We use the honey bee (Apis mellifera) to investigate how the ingestion of acute doses of caffeine before, during, and after conditioning influences performance in an appetitive olfactory learning and memory task. Consumption of caffeine doses of 0.01 M or greater during or prior to conditioning causes a significant reduction in response levels during acquisition. Although bees find the taste of caffeine to be aversive at high concentrations, the bitter taste does not explain the reduction in acquisition observed for bees fed caffeine before conditioning. While high doses of caffeine reduced performance during acquisition, the response levels of bees given caffeine were the same as those of the sucrose only control group in a recall test 24h after conditioning. In addition, caffeine administered after conditioning had no affect on recall. These results suggest that caffeine specifically affects performance during acquisition and not the processes involved in the formation of early long term memory. Copyright © 2012 Elsevier B.V. All rights reserved.
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Robery, Steven; Mukanowa, Janina; Percie du Sert, Nathalie; Andrews, Paul L R; Williams, Robin S B
2011-01-01
Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence reduce adverse animal experimentation in this area. Twenty eight emetic or taste aversive compounds were employed to investigate the acute (10 min) effect of compounds on Dictyostelium cell behaviour (shape, speed and direction of movement) in a shallow chemotaxic gradient (Dunn chamber). Compound concentrations were chosen based on those previously reported to be emetic or aversive in in vivo studies and results were recorded and quantified by automated image analysis. Dictyostelium cell motility was rapidly and strongly inhibited by four structurally distinct tastants (three bitter tasting compounds--denatonium benzoate, quinine hydrochloride, phenylthiourea, and the pungent constituent of chilli peppers--capsaicin). In addition, stomach irritants (copper chloride and copper sulphate), and a phosphodiesterase IV inhibitor also rapidly blocked movement. A concentration-dependant relationship was established for five of these compounds, showing potency of inhibition as capsaicin (IC(50) = 11.9 ± 4.0 µM) > quinine hydrochloride (IC(50) = 44.3 ± 6.8 µM) > denatonium benzoate (IC(50) = 129 ± 4 µM) > phenylthiourea (IC(50) = 366 ± 5 µM) > copper sulphate (IC(50) = 1433 ± 3 µM). In contrast, 21 compounds within the cytotoxic and receptor agonist/antagonist classes did not affect cell behaviour. Further analysis of bitter and pungent compounds showed that the effect on cell behaviour was reversible and not cytotoxic, suggesting an uncharacterised molecular mechanism of action for these compounds. These results therefore demonstrate that Dictyostelium has potential as a non-sentient model in the analysis of the molecular effects of tastants, although it has limited utility in identification of emetic agents in general.
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Rzepa, Ewelina; Fisk, Jennifer; McCabe, Ciara
2017-03-01
Neural reward function has been proposed as a possible biomarker for depression. However, how the neural response to reward and aversion might differ in young adolescents with current symptoms of depression is as yet unclear. Thirty-three adolescents were recruited, 17 scoring low on the Mood and Feelings Questionnaire (low risk group) and 16 scoring high (high risk group). Our functional magnetic resonance imaging task measured; anticipation (pleasant/unpleasant cue), effort (achieve a pleasant taste or avoid an unpleasant taste) and consummation (pleasant/unpleasant tastes) in regions of interest; ventral medial prefrontal cortex, pregenual cingulate cortex, the insula and ventral striatum. We also examined whole brain group differences. In the regions of interest analysis we found reduced activity in the high risk group in the pregenual cingulate cortex during anticipation and reduced pregenual cingulate cortex and ventral medial prefrontal cortex during effort and consummation. In the whole brain analysis we also found reduced activity in the high risk group in the prefrontal cortex and the precuneus during anticipation. We found reduced activity in the hippocampus during the effort phase and in the anterior cingulate/frontal pole during consummation in the high risk group. Increased anhedonia measures correlated with decreased pregenual cingulate cortex activity during consummation in the high risk group only. Our results are the first to show that adolescents with depression symptoms have blunted neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This study suggests that interventions in young people at risk of depression, that can reverse blunted responses, might be beneficial as preventative strategies.
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Latorre, Lucía; Larrinaga, Asier R; Santamaría, Luis
2013-01-01
Seabirds nesting on islands are threatened by invasive rodents, such as mice and rats, which may attack eggs, chicks and even adults. The low feasibility of rat eradications on many islands makes the development of alternate control plans necessary. We used a combination of field experiments on a Mediterranean island invaded by black rats (Rattusrattus) to evaluate (1) the predation risk posed to different-sized seabird eggs and (2), the potential of two deterrent methods (electronic and chemical) to reduce its impact. Rats were able to consume eggs of all sizes (12 to 68 g), but survival increased 13 times from the smallest to the largest eggs (which also had more resistant eggshells). Extrapolation to seabird eggs suggests that the smallest species (Hydrobatespelagicus) suffer the most severe predation risk, but even the largest (Larusmichahellis) could suffer >60% mortality. Nest attack was not reduced by the deterrents. However, chemical deterrence (conditioned taste aversion by lithium chloride) slowed the increase in predation rate over time, which resulted in a three-fold increase in egg survival to predation as compared to both control and electronic deterrence. At the end of the experimental period, this effect was confirmed by a treatment swap, which showed that conferred protection remains at least 15 days after cessation of the treatment. Results indicate that small seabird species are likely to suffer severe rates of nest predation by rats and that conditioned taste aversion, but not electronic repellents, may represent a suitable method to protect colonies when eradication or control is not feasible or cost-effective.
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Bitterness prediction in-silico: A step towards better drugs.
Bahia, Malkeet Singh; Nissim, Ido; Niv, Masha Y
2018-02-05
Bitter taste is innately aversive and thought to protect against consuming poisons. Bitter taste receptors (Tas2Rs) are G-protein coupled receptors, expressed both orally and extra-orally and proposed as novel targets for several indications, including asthma. Many clinical drugs elicit bitter taste, suggesting the possibility of drugs re-purposing. On the other hand, the bitter taste of medicine presents a major compliance problem for pediatric drugs. Thus, efficient tools for predicting, measuring and masking bitterness of active pharmaceutical ingredients (APIs) are required by the pharmaceutical industry. Here we highlight the BitterDB database of bitter compounds and survey the main computational approaches to prediction of bitter taste based on compound's chemical structure. Current in silico bitterness prediction methods provide encouraging results, can be constantly improved using growing experimental data, and present a reliable and efficient addition to the APIs development toolbox. Copyright © 2017 Elsevier B.V. All rights reserved.
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Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.
Anderson, Rachel I; Varlinskaya, Elena I; Spear, Linda P
2010-12-01
Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption. Copyright © 2010 by the Research Society on Alcoholism.
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Rorabaugh, Boyd; Seeley, Sarah; Evans, Mary; Marengo, Christina; D'Souza, Manoranjan
2017-06-09
The goal of the current study was to assess the effects of prenatal methamphetamine (MA)/saline exposure on nicotine-induced stimulant and aversive effects in both male and female adult rats. The aversive effects of nicotine were assessed using the nicotine-induced conditioned taste aversion model (0.4mg/kg, base), while the stimulant effects of nicotine were measured by assessing changes in spontaneous locomotor activity after subcutaneous administration of different doses of nicotine (0, 0.1 & 0.4mg/kg, base). The aversive effects of nicotine were significantly decreased in male, but not in female rats with a history of prenatal MA exposure compared to respective saline controls. No influence of prenatal MA exposure was observed on nicotine-induced increase in locomotor activity in either male or female rats. In conclusion, males with a history of prenatal MA exposure may be more vulnerable to nicotine addiction due to a decrease in nicotine-induced aversive effects. Copyright © 2017 Elsevier B.V. All rights reserved.
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Learning the specific quality of taste reinforcement in larval Drosophila
Schleyer, Michael; Miura, Daisuke; Tanimura, Teiichi; Gerber, Bertram
2015-01-01
The only property of reinforcement insects are commonly thought to learn about is its value. We show that larval Drosophila not only remember the value of reinforcement (How much?), but also its quality (What?). This is demonstrated both within the appetitive domain by using sugar vs amino acid as different reward qualities, and within the aversive domain by using bitter vs high-concentration salt as different qualities of punishment. From the available literature, such nuanced memories for the quality of reinforcement are unexpected and pose a challenge to present models of how insect memory is organized. Given that animals as simple as larval Drosophila, endowed with but 10,000 neurons, operate with both reinforcement value and quality, we suggest that both are fundamental aspects of mnemonic processing—in any brain. DOI: http://dx.doi.org/10.7554/eLife.04711.001 PMID:25622533
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Aversive Learning and Trait Aggression Influence Retaliatory Behavior.
Molapour, Tanaz; Lindström, Björn; Olsson, Andreas
2016-01-01
In two experiments (n = 35, n = 34), we used a modified fear-conditioning paradigm to investigate the role of aversive learning in retaliatory behavior in social context. Participants first completed an initial aversive learning phase in which the pairing of a neutral conditioned stimulus (CS; i.e., neutral face) with a naturally aversive unconditioned stimulus (US; electric shock) was learned. Then they were given an opportunity to interact (i.e., administer 0-2 shocks) with the same faces again, during a Test phase. In Experiment 2, we used the same paradigm with the addition of online trial-by-trial ratings (e.g., US expectancy and anger) to examine the role of aversive learning, anger, and the learned expectancy of receiving punishment more closely. Our results indicate that learned aversions influenced future retaliation in a social context. In both experiments, participants showed largest skin conductance responses (SCRs) to the faces paired with one or two shocks, demonstrating successful aversive learning. Importantly, participants administered more shocks to the faces paired with the most number of shocks when the opportunity was given during test. Also, our results revealed that aggressive traits (Buss and Perry Aggression scale) were associated with retaliation only toward CSs associated with aversive experiences. These two experiments show that aggressive traits, when paired with aversive learning experiences enhance the likelihood to act anti-socially toward others.
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Aversive Learning and Trait Aggression Influence Retaliatory Behavior
Molapour, Tanaz; Lindström, Björn; Olsson, Andreas
2016-01-01
In two experiments (n = 35, n = 34), we used a modified fear-conditioning paradigm to investigate the role of aversive learning in retaliatory behavior in social context. Participants first completed an initial aversive learning phase in which the pairing of a neutral conditioned stimulus (CS; i.e., neutral face) with a naturally aversive unconditioned stimulus (US; electric shock) was learned. Then they were given an opportunity to interact (i.e., administer 0–2 shocks) with the same faces again, during a Test phase. In Experiment 2, we used the same paradigm with the addition of online trial-by-trial ratings (e.g., US expectancy and anger) to examine the role of aversive learning, anger, and the learned expectancy of receiving punishment more closely. Our results indicate that learned aversions influenced future retaliation in a social context. In both experiments, participants showed largest skin conductance responses (SCRs) to the faces paired with one or two shocks, demonstrating successful aversive learning. Importantly, participants administered more shocks to the faces paired with the most number of shocks when the opportunity was given during test. Also, our results revealed that aggressive traits (Buss and Perry Aggression scale) were associated with retaliation only toward CSs associated with aversive experiences. These two experiments show that aggressive traits, when paired with aversive learning experiences enhance the likelihood to act anti-socially toward others. PMID:27375520
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Glendinning, John I; Davis, Adrienne; Ramaswamy, Sudha
2002-08-15
Animals can discriminate among many different types of foods. This discrimination process involves multiple sensory systems, but the sense of taste is known to play a central role. We asked how the taste system contributes to the discrimination of different "bitter" taste stimuli in Manduca sexta caterpillars. This insect has approximately eight bilateral pairs of taste cells that respond selectively to bitter taste stimuli. Each bilateral pair of bitter-sensitive taste cells has a different molecular receptive range (MRR); some of these taste cells also contain two signaling pathways with distinctive MRRs and temporal patterns of spiking. To test for discrimination, we habituated the caterpillar's taste-mediated aversive response to one bitter taste stimulus (salicin) and then asked whether this habituation phenomenon generalized to four other bitter taste stimuli (caffeine, aristolochic acid, Grindelia extract, and Canna extract). We inferred that the two compounds were discriminable if the habituation phenomenon failed to generalize (e.g., from salicin to aristolochic acid). We found that M. sexta could discriminate between salicin and those bitter taste stimuli that activate (1) different populations of bitter-sensitive taste cells (Grindelia extract and Canna extract) or (2) different signaling pathways within the same bitter-sensitive taste cell (aristolochic acid). M. sexta could not discriminate between salicin and a bitter taste stimulus that activates the same signaling pathway within the same bitter-sensitive taste cell (caffeine). We propose that the heterogeneous population of bitter-sensitive taste cells and signaling pathways within this insect facilitates the discrimination of bitter taste stimuli.
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Shoaib, M; Gommans, J; Morley, A; Stolerman, I P; Grailhe, R; Changeux, J-P
2002-03-01
The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. These experiments use mice lacking the beta2 subunit of nicotinic receptors to investigate its role in nicotine discrimination and conditioned taste aversion (CTA). Wild-type and mutant mice were trained either in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement, or in a counterbalanced two-flavour CTA procedure. Rates of lever-pressing of wild-type and mutant mice did not differ. Wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) rapidly and exhibited steep dose-response curves. Mutant mice failed to acquire these nicotine discriminations and exhibited flat dose-response curves. Both wild-type and mutant mice acquired discrimination of nicotine (1.6 mg/kg) although discrimination performance was weak in the mutants. Nicotine initially reduced response rates in wild-type and mutant mice, and tolerance developed to this effect in each genotype. Both genotypes acquired discrimination of morphine (3 mg/kg) with similar degrees of accuracy, and dose-response curves for morphine discrimination in the two genotypes were indistinguishable. Nicotine produced dose-related CTA in both genotypes, but the magnitude of the effect was less in the mutants than in the wild-type controls. It is concluded that nicotinic receptors containing the beta2 subunit play a major role in the discriminative stimulus and taste aversion effects of nicotine that may reflect psychological aspects of tobacco dependence. Such receptors appear to have a less crucial role in the response-rate, reducing effects of nicotine and in nicotine tolerance.
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Sweet and bitter taste in the brain of awake behaving animals
Peng, Yueqing; Gillis-Smith, Sarah; Jin, Hao; Tränkner, Dimitri; Ryba, Nicholas J. P.; Zuker, Charles S.
2015-01-01
Taste is responsible for evaluating the nutritious content of food, guiding essential appetitive behaviors, preventing the ingestion of toxic substances, and helping ensure the maintenance of a healthy diet. Sweet and bitter are two of the most salient sensory percepts for humans and other animals; sweet taste permits the identification of energy-rich nutrients while bitter warns against the intake of potentially noxious chemicals1. In mammals, information from taste receptor cells in the tongue is transmitted through multiple neural stations to the primary gustatory cortex in the brain2. Recent imaging studies have shown that sweet and bitter are represented in the primary gustatory cortex by neurons organized in a spatial map3,4, with each taste quality encoded by distinct cortical fields4. Here we demonstrate that by manipulating the brain fields representing sweet and bitter taste we directly control an animal’s internal representation, sensory perception, and behavioral actions. These results substantiate the segregation of taste qualities in the cortex, expose the innate nature of appetitive and aversive taste responses, and illustrate the ability of gustatory cortex to recapitulate complex behaviors in the absence of sensory input. PMID:26580015
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The ontogeny of ethanol aversion.
Saalfield, Jessica; Spear, Linda
2016-03-15
Recent work has suggested separate developmental periods within the broader framework of adolescence, with data suggesting distinct alterations and vulnerabilities within these intervals. While previous research has suggested reduced sensitivity to the aversive effects of alcohol in adolescence relative to adults, a more detailed ontogeny of this effect has yet to be conducted. The adolescent brain undergoes significant transitions throughout adolescence, including in regions linked with drug reward and aversion. The current study aimed to determine the ontogeny of ethanol aversion by utilizing a conditioned taste aversion procedure at six different ages to test the hypothesis that the transitions into, through, and out of adolescence are associated with ontogenetic alterations in sensitivity to the aversive properties of ethanol. Non-deprived animals given Boost® as the conditioned stimulus (CS) were used in Experiment 1, whereas Experiment 2 used water-restricted animals provided with a saccharin/sucrose solution as the CS. In both experiments, an attenuated sensitivity to the aversive properties of ethanol was evident in adolescents compared to adults, although more age differences were apparent in water deprived animals than when a highly palatable CS was given to ad libitum animals. Overall, the data suggest an attenuated sensitivity to the aversive properties of ethanol that is most pronounced during pre- and early adolescence, declining thereafter to reach the enhanced aversive sensitivity of adults. Copyright © 2016 Elsevier Inc. All rights reserved.
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Taste information derived from T1R-expressing taste cells in mice.
Yoshida, Ryusuke; Ninomiya, Yuzo
2016-03-01
The taste system of animals is used to detect valuable nutrients and harmful compounds in foods. In humans and mice, sweet, bitter, salty, sour and umami tastes are considered the five basic taste qualities. Sweet and umami tastes are mediated by G-protein-coupled receptors, belonging to the T1R (taste receptor type 1) family. This family consists of three members (T1R1, T1R2 and T1R3). They function as sweet or umami taste receptors by forming heterodimeric complexes, T1R1+T1R3 (umami) or T1R2+T1R3 (sweet). Receptors for each of the basic tastes are thought to be expressed exclusively in taste bud cells. Sweet (T1R2+T1R3-expressing) taste cells were thought to be segregated from umami (T1R1+T1R3-expressing) taste cells in taste buds. However, recent studies have revealed that a significant portion of taste cells in mice expressed all T1R subunits and responded to both sweet and umami compounds. This suggests that sweet and umami taste cells may not be segregated. Mice are able to discriminate between sweet and umami tastes, and both tastes contribute to behavioural preferences for sweet or umami compounds. There is growing evidence that T1R3 is also involved in behavioural avoidance of calcium tastes in mice, which implies that there may be a further population of T1R-expressing taste cells that mediate aversion to calcium taste. Therefore the simple view of detection and segregation of sweet and umami tastes by T1R-expressing taste cells, in mice, is now open to re-examination. © 2016 Authors; published by Portland Press Limited.
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Awata, Hiroko; Wakuda, Ryo; Ishimaru, Yoshiyasu; Matsuoka, Yuji; Terao, Kanta; Katata, Satomi; Matsumoto, Yukihisa; Hamanaka, Yoshitaka; Noji, Sumihare; Mito, Taro; Mizunami, Makoto
2016-01-01
Revealing reinforcing mechanisms in associative learning is important for elucidation of brain mechanisms of behavior. In mammals, dopamine neurons are thought to mediate both appetitive and aversive reinforcement signals. Studies using transgenic fruit-flies suggested that dopamine neurons mediate both appetitive and aversive reinforcements, through the Dop1 dopamine receptor, but our studies using octopamine and dopamine receptor antagonists and using Dop1 knockout crickets suggested that octopamine neurons mediate appetitive reinforcement and dopamine neurons mediate aversive reinforcement in associative learning in crickets. To fully resolve this issue, we examined the effects of silencing of expression of genes that code the OA1 octopamine receptor and Dop1 and Dop2 dopamine receptors by RNAi in crickets. OA1-silenced crickets exhibited impairment in appetitive learning with water but not in aversive learning with sodium chloride solution, while Dop1-silenced crickets exhibited impairment in aversive learning but not in appetitive learning. Dop2-silenced crickets showed normal scores in both appetitive learning and aversive learning. The results indicate that octopamine neurons mediate appetitive reinforcement via OA1 and that dopamine neurons mediate aversive reinforcement via Dop1 in crickets, providing decisive evidence that neurotransmitters and receptors that mediate appetitive reinforcement indeed differ among different species of insects. PMID:27412401
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Awata, Hiroko; Wakuda, Ryo; Ishimaru, Yoshiyasu; Matsuoka, Yuji; Terao, Kanta; Katata, Satomi; Matsumoto, Yukihisa; Hamanaka, Yoshitaka; Noji, Sumihare; Mito, Taro; Mizunami, Makoto
2016-07-14
Revealing reinforcing mechanisms in associative learning is important for elucidation of brain mechanisms of behavior. In mammals, dopamine neurons are thought to mediate both appetitive and aversive reinforcement signals. Studies using transgenic fruit-flies suggested that dopamine neurons mediate both appetitive and aversive reinforcements, through the Dop1 dopamine receptor, but our studies using octopamine and dopamine receptor antagonists and using Dop1 knockout crickets suggested that octopamine neurons mediate appetitive reinforcement and dopamine neurons mediate aversive reinforcement in associative learning in crickets. To fully resolve this issue, we examined the effects of silencing of expression of genes that code the OA1 octopamine receptor and Dop1 and Dop2 dopamine receptors by RNAi in crickets. OA1-silenced crickets exhibited impairment in appetitive learning with water but not in aversive learning with sodium chloride solution, while Dop1-silenced crickets exhibited impairment in aversive learning but not in appetitive learning. Dop2-silenced crickets showed normal scores in both appetitive learning and aversive learning. The results indicate that octopamine neurons mediate appetitive reinforcement via OA1 and that dopamine neurons mediate aversive reinforcement via Dop1 in crickets, providing decisive evidence that neurotransmitters and receptors that mediate appetitive reinforcement indeed differ among different species of insects.
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Sroubek, J; Hort, J; Komárek, V; Langmeier, M; Brozek, G
2001-01-01
The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned taste aversion (CTA), an important example of nondeclarative memory, was studied in adult Long Evans rats. Deterioration of CTA was studied during the silent period between pilocarpine-induced status epilepticus (SE) and delayed spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine (320 mg/kg ) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.). Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg i.p.), administered together with pilocarpine. CTA was formed against the salty taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed and tested during the silent period after SE. In the experiment of CTA retrieval, the CTA was acquired before SE and the retrieval itself was tested during the silent period. Retrieval of CTA acquired before SE was impaired more than the retrieval of CTA formed during the silent period. Our findings indicate that epileptic seizures can disrupt even non-declarative memory but that CTA formed by the damaged brain can use its better preserved parts for memory trace formation. Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced status epilepticus protected memory deterioration.
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ERIC Educational Resources Information Center
Marholin, D., II; And Others
1980-01-01
Two case studies are presented illustrating how the treatment program eliminated rumination with effects maintained 1 to 9 months following treatment, and how substantial weight gain was also demonstrated with one S who had previously lost weight. (Author/DLS)
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Larsen, Tobias; Collette, Sven; Tyszka, Julian M.; Seymour, Ben; O'Doherty, John P.
2015-01-01
The role of neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of the midbrain in contributing to the elicitation of reward prediction errors during appetitive learning has been well established. Less is known about the differential contribution of these midbrain regions to appetitive versus aversive learning, especially in humans. Here we scanned human participants with high-resolution fMRI focused on the SN and VTA while they participated in a sequential Pavlovian conditioning paradigm involving an appetitive outcome (a pleasant juice), as well as an aversive outcome (an unpleasant bitter and salty flavor). We found a degree of regional specialization within the SN: Whereas a region of ventromedial SN correlated with a temporal difference reward prediction error during appetitive Pavlovian learning, a dorsolateral area correlated instead with an aversive expected value signal in response to the most distal cue, and to a reward prediction error in response to the most proximal cue to the aversive outcome. Furthermore, participants' affective reactions to both the appetitive and aversive conditioned stimuli more than 1 year after the fMRI experiment was conducted correlated with activation in the ventromedial and dorsolateral SN obtained during the experiment, respectively. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts. SIGNIFICANCE STATEMENT The role of the substantia nigra (SN) and ventral tegmental area (VTA) in appetitive learning is well established, but less is known about their contribution to aversive compared with appetitive learning, especially in humans. We used high-resolution fMRI to measure activity in the SN and VTA while participants underwent higher-order Pavlovian learning. We found a regional specialization within the SN: a ventromedial area was selectively engaged during appetitive learning, and a dorsolateral area during aversive learning. Activity in these areas predicted affective reactions to appetitive and aversive conditioned stimuli over 1 year later. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts. PMID:26490862
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Visual Aversive Learning Compromises Sensory Discrimination.
Shalev, Lee; Paz, Rony; Avidan, Galia
2018-03-14
Aversive learning is thought to modulate perceptual thresholds, which can lead to overgeneralization. However, it remains undetermined whether this modulation is domain specific or a general effect. Moreover, despite the unique role of the visual modality in human perception, it is unclear whether this aspect of aversive learning exists in this modality. The current study was designed to examine the effect of visual aversive outcomes on the perception of basic visual and auditory features. We tested the ability of healthy participants, both males and females, to discriminate between neutral stimuli, before and after visual learning. In each experiment, neutral stimuli were associated with aversive images in an experimental group and with neutral images in a control group. Participants demonstrated a deterioration in discrimination (higher discrimination thresholds) only after aversive learning. This deterioration was measured for both auditory (tone frequency) and visual (orientation and contrast) features. The effect was replicated in five different experiments and lasted for at least 24 h. fMRI neural responses and pupil size were also measured during learning. We showed an increase in neural activations in the anterior cingulate cortex, insula, and amygdala during aversive compared with neutral learning. Interestingly, the early visual cortex showed increased brain activity during aversive compared with neutral context trials, with identical visual information. Our findings imply the existence of a central multimodal mechanism, which modulates early perceptual properties, following exposure to negative situations. Such a mechanism could contribute to abnormal responses that underlie anxiety states, even in new and safe environments. SIGNIFICANCE STATEMENT Using a visual aversive-learning paradigm, we found deteriorated discrimination abilities for visual and auditory stimuli that were associated with visual aversive stimuli. We showed increased neural activations in the anterior cingulate cortex, insula, and amygdala during aversive learning, compared with neutral learning. Importantly, similar findings were also evident in the early visual cortex during trials with aversive/neutral context, but with identical visual information. The demonstration of this phenomenon in the visual modality is important, as it provides support to the notion that aversive learning can influence perception via a central mechanism, independent of input modality. Given the dominance of the visual system in human perception, our findings hold relevance to daily life, as well as imply a potential etiology for anxiety disorders. Copyright © 2018 the authors 0270-6474/18/382766-14$15.00/0.
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Effects of 5-HT and insulin on learning and memory formation in food-deprived snails.
Aonuma, Hitoshi; Totani, Yuki; Kaneda, Mugiho; Nakamura, Ryota; Watanabe, Takayuki; Hatakeyama, Dai; Dyakonova, Varvara E; Lukowiak, Ken; Ito, Etsuro
2018-02-01
The pond snail Lymnaea stagnalis learns conditioned taste aversion (CTA) and consolidates it into long-term memory (LTM). How well they learn and form memory depends on the degree of food deprivation. Serotonin (5-HT) plays an important role in mediating feeding, and insulin enhances the memory consolidation process following CTA training. However, the relationship between these two signaling pathways has not been addressed. We measured the 5-HT content in the central nervous system (CNS) of snails subjected to different durations of food deprivation. One-day food-deprived snails, which exhibit the best learning and memory, had the lowest 5-HT content in the CNS, whereas 5-day food-deprived snails, which do not learn, had a high 5-HT content. Immersing 1-day food-deprived snails in 5-HT impaired learning and memory by causing an increase in 5-HT content, and that the injection of insulin into these snails reversed this impairment. We conclude that insulin rescues the CTA deficit and this may be due to a decrease in the 5-HT content in the CNS of Lymnaea. Copyright © 2018 Elsevier Inc. All rights reserved.
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Manuelian, Carmen L.; Albanell, Elena; Rovai, Maristela; Caja, Gerardo
2016-01-01
Conditioned taste aversion (CTA) is a learning behavior process where animals are trained to reject certain feed after gastrointestinal discomfort has been produced. Lithium chloride (LiCl) is the preferred agent used in livestock to induce CTA because it specifically stimulates the vomit center. In addition, LiCl is commercially available, and easy to prepare and administer using a drenching gun. Nevertheless, some factors have to be considered to obtain an effective long-lasting CTA, which allows small ruminants to graze during the cropping season. A key aspect is to use animals with no previous contact with the target plant (the plant chosen to be avoided; new feed). Due to their native neophobic feeding behavior, small ruminants can easily associate the negative feedback effects with the new feed, resulting in a strong and persistent CTA. The recommended doses are 200 and 225 mg LiCl/kg body weight (BW) for goats and sheep, respectively. To induce CTA, 100 g of the target plant should be individually offered for at least 30 min, and LiCl administered thereafter if the intake is greater than 10 g. Each time the animal eats the target plant without negative consequences, the CTA becomes weaker. Consequently, to minimize the risk of target plant consumption, it is essential to have sufficient palatable ground cover available. The presence of an alternative feed (of quality and quantity) prevents the accidental consumption of the target plant. A close monitoring of the flock is recommended to remove and re-dose any animal consuming more than 4 bites or 10 g of the target plant. At the beginning of each grazing season, check the CTA status of each animal before moving them to the crop. PMID:27167860
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NASA Astrophysics Data System (ADS)
Lin, Shih-Fan; Tsai, Yuan-Feen; Tai, Mei-Yun; Yeh, Kuei-Ying
2015-10-01
The present study examined the effects of short-term treatment with ovarian hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats were castrated and randomly divided into LiCl- and saline-treated groups. Nineteen days after castration, all of the animals were subjected to 23.5-h daily water deprivation for seven successive days (day 1 to day 7). On the conditioning day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose of saline injection immediately after administration of a 2 % sucrose solution during the 30-min water session. Starting from day 6, rats in both groups received one of the following treatments: daily subcutaneous injection of (1) estradiol alone (30 μg/kg; estradiol benzoate (E) group), (2) estradiol plus progesterone (500 μg; E + progesterone (P) group), or (3) olive oil. From day 9 to day 11, all of the rats were given daily two-bottle preference tests during the 30-min fluid session. The estradiol and estradiol plus progesterone treatments in the LiCl groups resulted in significantly lower preference scores for the sucrose solution compared with the olive oil treatment groups, but no difference in preference score was seen between these two groups. These results indicate that both the estradiol and estradiol plus progesterone treatments in the LiCl groups enhanced the acquisition of CTA learning and suggest that estradiol affects the acquisition of CTA mediated by an activational effect in male rats, whereas progesterone treatment does not influence the effects of estradiol on the acquisition of CTA.
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Xin, Jian; Ma, Ling; Zhang, Tian-Yi; Yu, Hui; Wang, Yue; Kong, Liang; Chen, Zhe-Yu
2014-05-21
Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in memory extinction. However, the detailed role of BDNF in memory extinction on the basis of neural circuit has not been fully understood. Here, we aim to investigate the role of BDNF signaling circuit in mediating conditioned taste aversion (CTA) memory extinction of the rats. We found region-specific changes in BDNF gene expression during CTA extinction. CTA extinction led to increased BDNF gene expression in the basolateral amygdala (BLA) and infralimbic prefrontal cortex (IL) but not in the central amygdaloid nucleus (CeA) and hippocampus (HIP). Moreover, blocking BDNF signaling or exogenous microinjection of BDNF into the BLA or IL could disrupt or enhance CTA extinction, which suggested that BDNF signaling in the BLA and IL is necessary and sufficient for CTA extinction. Interestingly, we found that microinjection of BDNF-neutralizing antibody into the BLA could abolish the extinction training-induced BDNF mRNA level increase in the IL, but not vice versa, demonstrating that BDNF signaling is transmitted from the BLA to IL during extinction. Finally, the accelerated extinction learning by infusion of exogenous BDNF in the BLA could also be blocked by IL infusion of BDNF-neutralizing antibody rather than vice versa, indicating that the IL, but not BLA, is the primary action site of BDNF in CTA extinction. Together, these data suggest that BLA-IL circuit regulates CTA memory extinction by identifying BDNF as a key regulator. Copyright © 2014 the authors 0270-6474/14/347302-12$15.00/0.
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Robery, Steven; Mukanowa, Janina; Percie du Sert, Nathalie; Andrews, Paul L. R.; Williams, Robin S. B.
2011-01-01
Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence reduce adverse animal experimentation in this area. Twenty eight emetic or taste aversive compounds were employed to investigate the acute (10 min) effect of compounds on Dictyostelium cell behaviour (shape, speed and direction of movement) in a shallow chemotaxic gradient (Dunn chamber). Compound concentrations were chosen based on those previously reported to be emetic or aversive in in vivo studies and results were recorded and quantified by automated image analysis. Dictyostelium cell motility was rapidly and strongly inhibited by four structurally distinct tastants (three bitter tasting compounds - denatonium benzoate, quinine hydrochloride, phenylthiourea, and the pungent constituent of chilli peppers - capsaicin). In addition, stomach irritants (copper chloride and copper sulphate), and a phosphodiesterase IV inhibitor also rapidly blocked movement. A concentration-dependant relationship was established for five of these compounds, showing potency of inhibition as capsaicin (IC50 = 11.9±4.0 µM) > quinine hydrochloride (IC50 = 44.3±6.8 µM) > denatonium benzoate (IC50 = 129±4 µM) > phenylthiourea (IC50 = 366±5 µM) > copper sulphate (IC50 = 1433±3 µM). In contrast, 21 compounds within the cytotoxic and receptor agonist/antagonist classes did not affect cell behaviour. Further analysis of bitter and pungent compounds showed that the effect on cell behaviour was reversible and not cytotoxic, suggesting an uncharacterised molecular mechanism of action for these compounds. These results therefore demonstrate that Dictyostelium has potential as a non-sentient model in the analysis of the molecular effects of tastants, although it has limited utility in identification of emetic agents in general. PMID:21931717
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Ward, Melissa; Norman, Haval; D'Souza, Manoranjan S
2018-02-15
Nicotine, an addictive component of tobacco smoke, produces both rewarding and aversive effects. Increasing the aversive effects of nicotine may help in promoting smoking cessation. However, neural targets mediating the aversive effects of nicotine have not been fully identified. In this study, we evaluated the role of kappa opioid receptors (KORs) in the aversive effects of nicotine (0.4 mg/kg, base; s.c.) using the nicotine-induced conditioned taste aversion (CTA) model in Wistar rats. The KORs were activated using the selective KOR agonist (±)U-50,488H (0, 0.03, 0.15 & 0.3mg/kg; s.c.) and inhibited using the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 15 & 30mg/kg; s.c.) in separate groups of rats using a between-subjects design. Pretreatment with the KOR agonist (±)U-50,488H (0.3mg/kg) significantly increased aversion for the nicotine-associated solution. Additionally, (±)U-50,488H (0.3mg/kg) on its own induced aversion to the flavored solution associated with it even in the absence of nicotine, suggesting that the KOR agonist induced increase in nicotine-induced aversion was an additive effect. Interestingly, administration of the KOR antagonist nor-BNI (30mg/kg) prior to conditioning with nicotine/saline, but not after conditioning with nicotine/saline, attenuated nicotine-induced aversive effects compared to saline controls. Taken together, these data suggest a role for KORs in the aversive effects of nicotine. Copyright © 2017 Elsevier B.V. All rights reserved.
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Lateral, not medial, prefrontal cortex contributes to punishment and aversive instrumental learning
Jean-Richard-dit-Bressel, Philip
2016-01-01
Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral agranular insular (RAIC), prelimbic (PL), and infralimbic (IL) cortex in instrumental aversive learning and decision-making. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused mild punishment (punished lever) but continued pressing the other lever that did not cause punishment (unpunished lever). Inactivations of OFC, RAIC, IL, or PL via the GABA agonists baclofen and muscimol (BM) had no effect on the acquisition of instrumental learning. OFC inactivations increased responding on the punished lever during expression of well-learned instrumental aversive learning, whereas RAIC inactivations increased responding on the punished lever when both levers were presented simultaneously in an unpunished choice test. There were few effects of medial PFC (PL and IL) inactivation. These results suggest that lateral PFC, notably OFC and RAIC, have complementary functions in aversive instrumental learning and decision-making; OFC is important for using established aversive instrumental memories to guide behavior away from actions that cause punishment, whereas RAIC is important for aversive decision-making under conditions of choice. PMID:27918280
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Acid sensing by sweet and bitter taste neurons in Drosophila melanogaster.
Charlu, Sandhya; Wisotsky, Zev; Medina, Adriana; Dahanukar, Anupama
2013-01-01
Drosophila melanogaster can taste various compounds and separate them into few basic categories such as sweet, bitter and salt taste. Here we investigate mechanisms underlying acid detection in Drosophila and report that the fly displays strong taste aversion to common carboxylic acids. We find that acid tastants act by the activation of a subset of bitter neurons and inhibition of sweet neurons. Bitter neurons begin to respond at pH 5 and show an increase in spike frequency as the extracellular pH drops, which does not rely on previously identified chemoreceptors. Notably, sweet neuron activity depends on the balance of sugar and acid tastant concentrations. This is independent of bitter neuron firing, and allows the fly to avoid acid-laced food sources even in the absence of functional bitter neurons. The two mechanisms may allow the fly to better evaluate the risk of ingesting acidic foods and modulate its feeding decisions accordingly.
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USDA-ARS?s Scientific Manuscript database
Insect kinins (leucokinins) are multifunctional peptides acting as neurohormones and neurotransmitters. In females of the mosquito vector Aedes aegypti (L.), aedeskinins are known to stimulate fluid secretion from the renal organs (Malpighian tubules) and hindgut contractions by activating a G prot...
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Holstein, Sarah E; Spanos, Marina; Hodge, Clyde W
2011-10-01
Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA). Binge-like alcohol consumption was investigated in adolescent (4 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with the intake of a novel tastant (NaCl). Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. These results indicate that adolescent mice consume more alcohol, per kilogram body weight, than adults in a binge-like model of alcohol drinking and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during adolescence occurs, in part, via a reduced sensitivity to the aversive properties of alcohol. Copyright © 2011 by the Research Society on Alcoholism.
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Holstein, Sarah E.; Spanos, Marina; Hodge, Clyde W.
2011-01-01
Background Binge alcohol drinking during adolescence is a serious health problem which may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA). Methods Binge-like alcohol consumption was investigated in adolescent (4 wk) and adult (10 wk) male C57BL/6J mice for 2-4 h/day for 16 d. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with intake of a novel tastant (NaCl). Results Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. Conclusions These results indicate that adolescent mice consume more alcohol, per kg body weight, than adults in a binge-like model of alcohol drinking, and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during adolescence occurs, in part, via a reduced sensitivity to the aversive properties of alcohol. PMID:21575017
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Saalfield, Jessica; Spear, Linda
2015-01-01
Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences.. Recent evidence suggests that adolescents are less sensitive than adults to ethanol’s aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4 g/kg i.g. ethanol (25%) or water every 48 hours from postnatal day (P) 25–45 (early AIE) or P45–65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5 g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. PMID:25698309
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Stevenson, Richard J; Mahmut, Mehmet K
2011-10-01
Odor "sweetness" may arise from experiencing odors and tastes together, resulting in a flavor memory that is later reaccessed by the odor. Forming a flavor memory may be impaired if the taste and odor elements are apparent during exposure, suggesting that configural processing may underpin learning. Using a new procedure, participants made actual flavor discriminations for one odor-taste pair (e.g., Taste A vs. Odor X-Taste A) and mock discriminations for another (e.g., Odor Y-Taste B vs. Odor Y-Taste B). Participants, who were successful at detecting the actual flavor discriminations, demonstrated equal amounts of learning for both odor-taste pairings. These results suggest that although a capacity to discriminate flavor into its elements may be necessary to support learning, whether participants experience a configural or elemental flavor representation may not.
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The Neural Foundations of Reaction and Action in Aversive Motivation.
Campese, Vincent D; Sears, Robert M; Moscarello, Justin M; Diaz-Mataix, Lorenzo; Cain, Christopher K; LeDoux, Joseph E
2016-01-01
Much of the early research in aversive learning concerned motivation and reinforcement in avoidance conditioning and related paradigms. When the field transitioned toward the focus on Pavlovian threat conditioning in isolation, this paved the way for the clear understanding of the psychological principles and neural and molecular mechanisms responsible for this type of learning and memory that has unfolded over recent decades. Currently, avoidance conditioning is being revisited, and with what has been learned about associative aversive learning, rapid progress is being made. We review, below, the literature on the neural substrates critical for learning in instrumental active avoidance tasks and conditioned aversive motivation.
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Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a NOEL equal to 5mg/kg. The mechanism for these effects ...
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Lateral, Not Medial, Prefrontal Cortex Contributes to Punishment and Aversive Instrumental Learning
ERIC Educational Resources Information Center
Jean-Richard-dit-Bressel , Philip; McNally, Gavan P.
2016-01-01
Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral…
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Wang, Yue; Zhang, Tian-Yi; Xin, Jian; Li, Ting; Yu, Hui; Li, Na; Chen, Zhe-Yu
2012-01-01
Consolidated memory can re-enter states of transient instability following reactivation, which is referred to as reconsolidation, and the exact molecular mechanisms underlying this process remain unexplored. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity and memory processes. We have recently observed that BDNF signaling in the central nuclei of the amygdala (CeA) and insular cortex (IC) was involved in the consolidation of conditioned taste aversion (CTA) memory. However, whether BDNF in the CeA or IC is required for memory reconsolidation is still unclear. In the present study, using a CTA memory paradigm, we observed increased BDNF expression in the IC but not in the CeA during CTA reconsolidation. We further determined that BDNF synthesis and signaling in the IC but not in the CeA was required for memory reconsolidation. The differential, spatial-specific roles of BDNF in memory consolidation and reconsolidation suggest that dissociative molecular mechanisms underlie reconsolidation and consolidation, which might provide novel targets for manipulating newly encoded and reactivated memories without causing universal amnesia. PMID:23185492
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The role of taste in alcohol preference, consumption and risk behavior.
Thibodeau, Margaret; Pickering, Gary J
2017-10-05
Alcohol consumption is widespread, and high levels of use are associated with increased risk of developing an alcohol use disorder. Thus, understanding the factors that influence alcohol intake is important for disease prevention and management. Additionally, elucidating the factors that associate with alcohol preference and intake in non-clinical populations allows for product development and optimisation opportunities for the alcoholic beverage industry. The literature on how taste (orosensation) influences alcohol behavior is critically appraised in this review. Ethanol, the compound common to all alcoholic beverages, is generally aversive as it primarily elicits bitterness and irritation when ingested. Individuals who experience orosensations (both taste and chemesthetic) more intensely tend to report lower liking and consumption of alcoholic beverages. Additionally, a preference for sweetness is likely associated with a paternal history of alcohol use disorders. However, conflicting findings in the literature are common and may be partially attributable to differences in the methods used to access orosensory responsiveness and taste phenotypes. We conclude that while taste is a key driver in alcohol preference, intake and use disorder, no single taste-related factor can adequately predict alcohol behaviour. Areas for further research and suggestions for improved methodological and analytical approaches are highlighted.
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BitterDB: a database of bitter compounds
Wiener, Ayana; Shudler, Marina; Levit, Anat; Niv, Masha Y.
2012-01-01
Basic taste qualities like sour, salty, sweet, bitter and umami serve specific functions in identifying food components found in the diet of humans and animals, and are recognized by proteins in the oral cavity. Recognition of bitter taste and aversion to it are thought to protect the organism against the ingestion of poisonous food compounds, which are often bitter. Interestingly, bitter taste receptors are expressed not only in the mouth but also in extraoral tissues, such as the gastrointestinal tract, indicating that they may play a role in digestive and metabolic processes. BitterDB database, available at http://bitterdb.agri.huji.ac.il/bitterdb/, includes over 550 compounds that were reported to taste bitter to humans. The compounds can be searched by name, chemical structure, similarity to other bitter compounds, association with a particular human bitter taste receptor, and so on. The database also contains information on mutations in bitter taste receptors that were shown to influence receptor activation by bitter compounds. The aim of BitterDB is to facilitate studying the chemical features associated with bitterness. These studies may contribute to predicting bitterness of unknown compounds, predicting ligands for bitter receptors from different species and rational design of bitterness modulators. PMID:21940398
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Sorokowska, Agnieszka; Pellegrino, Robert; Butovskaya, Marina; Marczak, Michalina; Niemczyk, Agnieszka; Huanca, Tomas; Sorokowski, Piotr
2017-09-01
Biological significance of food components suggests that preferences for basic tastes should be similar across cultures. On the other hand, cultural factors play an important role in diet and can consequently influence individual preference for food. To date, very few studies have compared basic tastes preferences among populations of very diverse environmental and cultural conditions, and research rather did not involve traditional populations for whom the biological significance of different food components might be the most pronounced. Hence, our study focused on basic taste preferences in three populations, covering a broad difference in diet due to environmental and cultural conditions, market availability, dietary habits and food acquirement: 1) a modern society (Poles, n = 200), 2) forager-horticulturalists from Amazon/Bolivia (Tsimane', n = 138), and 3) hunter-gatherers from Tanzania (Hadza, n = 85). The preferences for basic tastes were measured with sprays containing supra-threshold levels of sweet, sour, bitter, salty, and umami taste solutions. We observed several interesting differences between participating societies. We found that Tsimane' and Polish participants liked the sweet taste more than other tastes, while Hadza participants liked salty and sour tastes more than the remaining tastes. Further, Polish people found bitter taste particularly aversive, which was not observed in the traditional societies. Interestingly, no cross-cultural differences were observed for relative liking of umami taste - it was rated closely to neutral by members of all participating societies. Additionally, Hadza showed a pattern to like basic tastes that are more common to their current diet than societies with access to different food sources. These findings demonstrate the impact of diet and market availability on preference for basic tastes. Copyright © 2017 Elsevier Ltd. All rights reserved.
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2013-01-01
Temperature modulates the peripheral taste response of many animals, in part by activating transient receptor potential (Trp) cation channels. We hypothesized that temperature would also modulate peripheral taste responses in larval Manduca sexta. We recorded excitatory responses of the lateral and medial styloconic sensilla to chemical stimuli at 14, 22, and 30 °C. The excitatory responses to 5 chemical stimuli—a salt (KCl), 3 sugars (sucrose, glucose, and inositol) and an alkaloid (caffeine)—were unaffected by temperature. In contrast, the excitatory response to the aversive compound, aristolochic acid (AA), increased robustly with temperature. Next, we asked whether TrpA1 mediates the thermally dependent taste response to AA. To this end, we 1) identified a TrpA1 gene in M. sexta; 2) demonstrated expression of TrpA1 in the lateral and medial styloconic sensilla; 3) determined that 2 TrpA1 antagonists (HC-030031 and mecamylamine) inhibit the taste response to AA, but not caffeine; and then 4) established that the thermal dependence of the taste response to AA is blocked by HC-030031. Taken together, our results indicate that TrpA1 serves as a molecular integrator of taste and temperature in M. sexta. PMID:23828906
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Phenotypic transformation affects associative learning in the desert locust.
Simões, Patrício M V; Niven, Jeremy E; Ott, Swidbert R
2013-12-02
In desert locusts, increased population densities drive phenotypic transformation from the solitarious to the gregarious phase within a generation [1-4]. Here we show that when presented with odor-food associations, the two extreme phases differ in aversive but not appetitive associative learning, with solitarious locusts showing a conditioned aversion more quickly than gregarious locusts. The acquisition of new learned aversions was blocked entirely in acutely crowded solitarious (transiens) locusts, whereas appetitive learning and prior learned associations were unaffected. These differences in aversive learning support phase-specific feeding strategies. Associative training with hyoscyamine, a plant alkaloid found in the locusts' habitat [5, 6], elicits a phase-dependent odor preference: solitarious locusts avoid an odor associated with hyoscyamine, whereas gregarious locusts do not. Remarkably, when solitarious locusts are crowded and then reconditioned with the odor-hyoscyamine pairing as transiens, the specific blockade of aversive acquisition enables them to override their prior aversive memory with an appetitive one. Under fierce food competition, as occurs during crowding in the field, this provides a neuroecological mechanism enabling locusts to reassign an appetitive value to an odor that they learned previously to avoid. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Silver acetate interactions with nicotine and non-nicotine smoke components.
Rose, Jed E; Behm, Frédérique M; Murugesan, Thangaraju; McClernon, F Joseph
2010-12-01
Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment. PsycINFO Database Record (c) 2010 APA, all rights reserved.
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Orr, T Edward; Whitford-Stoddard, Jennifer L; Elkins, Ralph L
2004-05-01
Taste-aversion (TA)-prone (TAP) rats and TA-resistant (TAR) rats have been developed by means of bidirectional selective breeding on the basis of their behavioral responses to a TA conditioning paradigm. The TA conditioning involved the pairing of an emetic-class agent (cyclophosphamide) with a novel saccharin solution as the conditioned stimulus. Despite the absence of ethanol in the selective breeding process, these rat lines differ widely in ethanol self-administration. In the current study, blood alcohol concentrations (BACs) were determined after 9 days of limited (2 h per day) access to a simultaneous, two-bottle choice of a 10% ethanol in water solution [volume/volume (vol./vol.)] or plain water. The BACs correlated highly with ethanol intake among TAR rats, but an insufficient number of TAP rats yielded measurable BACs to make the same comparison within this rat line. The same rats were subsequently exposed to 24-h access of a two-bottle choice (10% ethanol or plain water) for 8 days. Ethanol consumption during the 24-h access period correlated highly with that seen during limited access. Subsequent TA conditioning with these rats yielded line-typical differences in saccharin preferences. In a separate group of rats, ethanol clearance was determined by measuring BACs at 1, 4, and 7 h after injection of a 2.5-g/kg dose of ethanol. Ethanol clearance was not different between the two lines. Furthermore, the lines did not differ with respect to food and water consumption. Therefore, the TAP rat-TAR rat differences in ethanol consumption cannot be attributed to line differences in ethanol metabolism or in general consummatory behavior. The findings support our contention that the line differences in ethanol consumption are mediated by differences in TA-related mechanisms. The findings are discussed with respect to genetically based differences in the subjective experience of ethanol.
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Ionotropic Receptor 76b Is Required for Gustatory Aversion to Excessive Na+ in Drosophila.
Lee, Min Jung; Sung, Ha Yeon; Jo, HyunJi; Kim, Hyung-Wook; Choi, Min Sung; Kwon, Jae Young; Kang, KyeongJin
2017-10-01
Avoiding ingestion of excessively salty food is essential for cation homeostasis that underlies various physiological processes in organisms. The molecular and cellular basis of the aversive salt taste, however, remains elusive. Through a behavioral reverse genetic screening, we discover that feeding suppression by Na + -rich food requires Ionotropic Receptor 76b ( Ir76b ) in Drosophila labellar gustatory receptor neurons (GRNs). Concentrated sodium solutions with various anions caused feeding suppression dependent on Ir76b . Feeding aversion to caffeine and high concentrations of divalent cations and sorbitol was unimpaired in Ir76b -deficient animals, indicating sensory specificity of Ir76b- dependent Na + detection and the irrelevance of hyperosmolarity-driven mechanosensation to Ir76b -mediated feeding aversion. Ir76b -dependent Na + -sensing GRNs in both L- and s-bristles are required for repulsion as opposed to the previous report where the L-bristle GRNs direct only low-Na + attraction. Our work extends the physiological implications of Ir76b from low-Na + attraction to high-Na + aversion, prompting further investigation of the physiological mechanisms that modulate two competing components of Na + -evoked gustation coded in heterogeneous Ir76b -positive GRNs.
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Taste Changes in Vitamin A Deficiency
Bernard, Rudy A.; Halpern, Bruce P.
1968-01-01
Taste preferences were studied in two groups of rats depleted of vitamin A by dietary restriction. One group received sufficient vitamin A acid supplement to maintain normal growth. The other group was repleted with vitamin A alcohol after the classical deficiency symptoms had appeared; this group gradually lost normal preferences for NaCl and aversion to quinine solutions during depletion. Vitamin A alcohol repletion tended to restore taste preferences to normal. In contrast, the group receiving vitamin A acid showed normal taste preferences throughout the depletion period. When the vitamin A acid supplement was removed taste preferences became abnormal and returned to normal when vitamin A acid was restored. Peripheral gustatory neural activity of depleted rats without any form of vitamin A was less than normal both at rest and when the tongue was stimulated with NaCl solutions. Histological examination showed keratin infiltrating the pores of the taste buds. Accessory glandular tissues were atrophied and debris filled the trenches of the papillae. It is concluded that vitamin A acid can provide the vitamin A required for normal taste, as contrasted with its inability to maintain visual function. It is suggested that the effect of vitamin A is exerted at the receptor level, as a result of its role in the biosynthesis of mucopolysaccharides, which have been recently identified in the pore area of taste buds, as well as being present in the various secretions of the oral cavity. PMID:4299794
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Krause, Mark A
2015-07-01
Inquiry into evolutionary adaptations has flourished since the modern synthesis of evolutionary biology. Comparative methods, genetic techniques, and various experimental and modeling approaches are used to test adaptive hypotheses. In psychology, the concept of adaptation is broadly applied and is central to comparative psychology and cognition. The concept of an adaptive specialization of learning is a proposed account for exceptions to general learning processes, as seen in studies of Pavlovian conditioning of taste aversions, sexual responses, and fear. The evidence generally consists of selective associations forming between biologically relevant conditioned and unconditioned stimuli, with conditioned responses differing in magnitude, persistence, or other measures relative to non-biologically relevant stimuli. Selective associations for biologically relevant stimuli may suggest adaptive specializations of learning, but do not necessarily confirm adaptive hypotheses as conceived of in evolutionary biology. Exceptions to general learning processes do not necessarily default to an adaptive specialization explanation, even if experimental results "make biological sense". This paper examines the degree to which hypotheses of adaptive specializations of learning in sexual and fear response systems have been tested using methodologies developed in evolutionary biology (e.g., comparative methods, quantitative and molecular genetics, survival experiments). A broader aim is to offer perspectives from evolutionary biology for testing adaptive hypotheses in psychological science.
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Kissing bugs can generalize and discriminate between different bitter compounds.
Asparch, Yamila; Pontes, Gina; Masagué, Santiago; Minoli, Sebastian; Barrozo, Romina B
2016-10-01
Animals make use of contact chemoreception structures to examine the quality of potential food sources. During this evaluation they can detect nutritious compounds that promote feeding and recognize toxins that trigger evasive behaviors. Although animals can easily distinguish between stimuli of different gustatory qualities (bitter, salty, sweet, etc.), their ability to discriminate between compounds of the same quality may be limited. Numerous plants produce alkaloids, compounds that elicit aversive behaviors in phytophagous insects and almost uniformly evoke a bitter taste for man. In hematophagous insects, however, the effect of feeding deterrent molecules has been barely studied. Recent studies showed that feeding in Rhodnius prolixus can be negatively modulated by the presence of alkaloids such as quinine (QUI) and caffeine (CAF), compounds that elicit similar aversive responses. Here, we applied associative and non-associative learning paradigms to examine under two behavioral contexts the ability of R. prolixus to distinguish, discriminate and/or generalize between these two bitter compounds, QUI and CAF. Our results show that bugs innately repelled by bitter compounds can change their behavior from avoidance to indifference or even to preference according to their previous experiences. After an aversive operant conditioning with QUI or CAF, R. prolixus modified its behavior in a direct but also in a cross-compound manner, suggesting the occurrence of a generalization process between these two alkaloids. Conversely, after a long pre-exposure to each alkaloid, bugs decreased their avoidance to the compound used during pre-exposure but still expressed an avoidance of the novel compound, proving that QUI and CAF are detected separately. Our results suggest that R. prolixus is able to discriminate between QUI and CAF, although after an associative conditioning they express a symmetrical cross-generalization. This kind of studies adds insight into the gustatory sense of a blood-sucking model but also into the learning abilities of hematophagous insects. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Saalfield, Jessica; Spear, Linda
2015-12-01
Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Singer, Philipp; Wei, Catherine J.; Chen, Jiang-Fan; Boison, Detlev; Yee, Benjamin K.
2013-01-01
Following early clinical leads, the adenosine A2AR receptor (A2AR) has continued to attract attention as a potential novel target for treating schizophrenia; especially against the negative and cognitive symptoms of the disease because of A2AR’s unique modulatory action over glutamatergic in addition to dopaminergic signaling. Through the antagonistic interaction with the dopamine D2 receptor, and by regulating glutamate release and N-methyl-d-aspartate receptor function, striatal A2AR is ideally positioned to fine-tune the dopamine-glutamate balance whose disturbance is implicated in the pathophysiology of schizophrenia. However, the precise function of striatal A2ARsin the regulation of schizophrenia-relevant behavior is poorly understood. Here, we tested the impact of conditional striatum-specific A2AR knockout (st-A2AR-KO) on latent inhibition (LI) and prepulse inhibition (PPI) – behavior that is tightly regulated by striatal dopamine and glutamate. These are two common cross-species translational tests for the assessment of selective attention and sensorimotor gating deficits reported in schizophrenia patients; and enhanced performance in these tests is associated with antipsychotic drug action. We found that neither LI nor PPI was significantly affected in st-A2AR-KO mice; although a deficit in active avoidance learning was identified in these animals. The latter phenotype, however, was not replicated in another form of aversive conditioning – conditioned taste aversion. Hence, the present study shows that neither learned inattention (as measured by LI) nor sensory gating (as indexed by PPI) requires the integrity of striatal A2ARs– a finding that may undermine the hypothesized importance of A2AR in the genesis and/or treatment of schizophrenia. PMID:23276608
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Sensory Cortical Population Dynamics Uniquely Track Behavior across Learning and Extinction
Katz, Donald B.
2014-01-01
Neural responses in many cortical regions encode information relevant to behavior: information that necessarily changes as that behavior changes with learning. Although such responses are reasonably theorized to be related to behavior causation, the true nature of that relationship cannot be clarified by simple learning studies, which show primarily that responses change with experience. Neural activity that truly tracks behavior (as opposed to simply changing with experience) will not only change with learning but also change back when that learning is extinguished. Here, we directly probed for this pattern, recording the activity of ensembles of gustatory cortical single neurons as rats that normally consumed sucrose avidly were trained first to reject it (i.e., conditioned taste aversion learning) and then to enjoy it again (i.e., extinction), all within 49 h. Both learning and extinction altered cortical responses, consistent with the suggestion (based on indirect evidence) that extinction is a novel form of learning. But despite the fact that, as expected, postextinction single-neuron responses did not resemble “naive responses,” ensemble response dynamics changed with learning and reverted with extinction: both the speed of stimulus processing and the relationships among ensemble responses to the different stimuli tracked behavioral relevance. These data suggest that population coding is linked to behavior with a fidelity that single-neuron coding is not. PMID:24453316
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Silvers, Jennifer A; Lumian, Daniel S; Gabard-Durnam, Laurel; Gee, Dylan G; Goff, Bonnie; Fareri, Dominic S; Caldera, Christina; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Tottenham, Nim
2016-06-15
Early institutional care can be profoundly stressful for the human infant, and, as such, can lead to significant alterations in brain development. In animal models, similar variants of early adversity have been shown to modify amygdala-hippocampal-prefrontal cortex development and associated aversive learning. The current study examined this rearing aberration in human development. Eighty-nine children and adolescents who were either previously institutionalized (PI youth; N = 46; 33 females and 13 males; age range, 7-16 years) or were raised by their biological parents from birth (N = 43; 22 females and 21 males; age range, 7-16 years) completed an aversive-learning paradigm while undergoing functional neuroimaging, wherein visual cues were paired with either an aversive sound (CS+) or no sound (CS-). For the PI youth, better aversive learning was associated with higher concurrent trait anxiety. Both groups showed robust learning and amygdala activation for CS+ versus CS- trials. However, PI youth also exhibited broader recruitment of several regions and increased hippocampal connectivity with prefrontal cortex. Stronger connectivity between the hippocampus and ventromedial PFC predicted significant improvements in future anxiety (measured 2 years later), and this was particularly true within the PI group. These results suggest that for humans as well as for other species, early adversity alters the neurobiology of aversive learning by engaging a broader prefrontal-subcortical circuit than same-aged peers. These differences are interpreted as ontogenetic adaptations and potential sources of resilience. Prior institutionalization is a significant form of early adversity. While nonhuman animal research suggests that early adversity alters aversive learning and associated neurocircuitry, no prior work has examined this in humans. Here, we show that youth who experienced prior institutionalization, but not comparison youth, recruit the hippocampus during aversive learning. Among youth who experienced prior institutionalization, individual differences in aversive learning were associated with worse current anxiety. However, connectivity between the hippocampus and prefrontal cortex prospectively predicted significant improvements in anxiety 2 years following scanning for previously institutionalized youth. Among youth who experienced prior institutionalization, age-atypical engagement of a distributed set of brain regions during aversive learning may serve a protective function. Copyright © 2016 the authors 0270-6474/16/366421-11$15.00/0.
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ERIC Educational Resources Information Center
Pineno, Oskar
2007-01-01
One conditioned taste aversion experiment with rats assessed the impact of extinguishing a target conditioned stimulus (CS), S, in compound with a second CS, A, upon conditioned responding elicited by CS S when presented alone at test. Following initial conditioning treatment with CSs A and S, the experiment manipulated number of extinction trials…
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Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a LOEL of 12.5mg/kg. The mechanism for these effects is unk...
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Fear of losing money? Aversive conditioning with secondary reinforcers.
Delgado, M R; Labouliere, C D; Phelps, E A
2006-12-01
Money is a secondary reinforcer that acquires its value through social communication and interaction. In everyday human behavior and laboratory studies, money has been shown to influence appetitive or reward learning. It is unclear, however, if money has a similar impact on aversive learning. The goal of this study was to investigate the efficacy of money in aversive learning, comparing it with primary reinforcers that are traditionally used in fear conditioning paradigms. A series of experiments were conducted in which participants initially played a gambling game that led to a monetary gain. They were then presented with an aversive conditioning paradigm, with either shock (primary reinforcer) or loss of money (secondary reinforcer) as the unconditioned stimulus. Skin conductance responses and subjective ratings indicated that potential monetary loss modulated the conditioned response. Depending on the presentation context, the secondary reinforcer was as effective as the primary reinforcer during aversive conditioning. These results suggest that stimuli that acquire reinforcing properties through social communication and interaction, such as money, can effectively influence aversive learning.
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A High Throughput In Vivo Assay for Taste Quality and Palatability
Palmer, R. Kyle; Long, Daniel; Brennan, Francis; Buber, Tulu; Bryant, Robert; Salemme, F. Raymond
2013-01-01
Taste quality and palatability are two of the most important properties measured in the evaluation of taste stimuli. Human panels can report both aspects, but are of limited experimental flexibility and throughput capacity. Relatively efficient animal models for taste evaluation have been developed, but each of them is designed to measure either taste quality or palatability as independent experimental endpoints. We present here a new apparatus and method for high throughput quantification of both taste quality and palatability using rats in an operant taste discrimination paradigm. Cohorts of four rats were trained in a modified operant chamber to sample taste stimuli by licking solutions from a 96-well plate that moved in a randomized pattern beneath the chamber floor. As a rat’s tongue entered the well it disrupted a laser beam projecting across the top of the 96-well plate, consequently producing two retractable levers that operated a pellet dispenser. The taste of sucrose was associated with food reinforcement by presses on a sucrose-designated lever, whereas the taste of water and other basic tastes were associated with the alternative lever. Each disruption of the laser was counted as a lick. Using this procedure, rats were trained to discriminate 100 mM sucrose from water, quinine, citric acid, and NaCl with 90-100% accuracy. Palatability was determined by the number of licks per trial and, due to intermediate rates of licking for water, was quantifiable along the entire spectrum of appetitiveness to aversiveness. All 96 samples were evaluated within 90 minute test sessions with no evidence of desensitization or fatigue. The technology is capable of generating multiple concentration–response functions within a single session, is suitable for in vivo primary screening of tastant libraries, and potentially can be used to evaluate stimuli for any taste system. PMID:23951319
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Ozaki, Mamiko; Takahara, Teruhiko; Kawahara, Yasuhiro; Wada-Katsumata, Ayako; Seno, Keiji; Amakawa, Taisaku; Yamaoka, Ryohei; Nakamura, Tadashi
2003-05-01
The blowfly, Phormia regina, has sensilla with four contact-chemoreceptor cells and one mechanoreceptor cell on its labellum. Three of the four chemoreceptor cells are called the sugar, the salt and the water receptor cells, respectively. However, the specificity of the remaining chemoreceptor cell, traditionally called the "fifth cell", has not yet been clarified. Referring to behavioral evaluation of the oral toxicity of monoterpenes, we measured the electrophysiological response of the "fifth cell" to these compounds. Of all the monoterpenes examined, D-limonene exhibited the strongest oral toxicity and induced the severest aversive behavior with vomiting and/or excretion in the fly. D-Limonene, when dispersed in an aqueous stimulus solution including dimethyl sulfoxide or an odorant-binding protein (OBP) found in the contact-chemoreceptor sensillum, the chemical sense-related lipophilic ligand-binding protein (CRLBP), evoked impulses from the "fifth cell". Considering the relationship between the aversive effects of monoterpenes and the response of the "fifth cell" to these effects, we propose that the "fifth cell" is a warning cell that has been differentiated as a taste system for detecting and avoiding dangerous foods. Here we suggest that in the insect contact-chemoreceptor sensillum, CRLBP carries lipophilic members of the noxious taste substances to the "fifth cell" through the aqueous sensillum lymph. This insect OBP may functionally be analogous to the von Ebner's grand protein in taste organs of mammals.
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The frequency of dietary references in homeopathic consultations.
Filho, Rubens Dolce
2011-07-01
A retrospective quantitative study on dietary references found in medical records of 2753 patients attending consultations from 10/1/1994 to 5/31/2007 was conducted. The symptoms found in the rubrics relating to food and drink aggravation and amelioration, aversion and craving of homeopathic repertories reflect diets at different places and times and do not correspond fully, to contemporary gastronomy. Desires for sweet and spicy foods were statistically more frequent, revealing the prevailing taste for such food among the studied population. Food cravings should be carefully analyzed before considering them as indications for choosing homeopathic therapy, they are less significant than aversions, aggravations and ameliorations. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Junca, Pierre; Carcaud, Julie; Moulin, Sibyle; Garnery, Lionel; Sandoz, Jean-Christophe
2014-01-01
In Pavlovian conditioning, animals learn to associate initially neutral stimuli with positive or negative outcomes, leading to appetitive and aversive learning respectively. The honeybee (Apis mellifera) is a prominent invertebrate model for studying both versions of olfactory learning and for unraveling the influence of genotype. As a queen bee mates with about 15 males, her worker offspring belong to as many, genetically-different patrilines. While the genetic dependency of appetitive learning is well established in bees, it is not the case for aversive learning, as a robust protocol was only developed recently. In the original conditioning of the sting extension response (SER), bees learn to associate an odor (conditioned stimulus - CS) with an electric shock (unconditioned stimulus - US). This US is however not a natural stimulus for bees, which may represent a potential caveat for dissecting the genetics underlying aversive learning. We thus first tested heat as a potential new US for SER conditioning. We show that thermal stimulation of several sensory structures on the bee’s body triggers the SER, in a temperature-dependent manner. Moreover, heat applied to the antennae, mouthparts or legs is an efficient US for SER conditioning. Then, using microsatellite analysis, we analyzed heat sensitivity and aversive learning performances in ten worker patrilines issued from a naturally inseminated queen. We demonstrate a strong influence of genotype on aversive learning, possibly indicating the existence of a genetic determinism of this capacity. Such determinism could be instrumental for efficient task partitioning within the hive. PMID:24828422
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Thompson, John A.
2016-01-01
The marker of neuronal activation, c-Fos, can be used to visualize spatial patterns of neural activity in response to taste stimulation. Because animals will not voluntarily consume aversive tastes, these stimuli are infused directly into the oral cavity via intraoral cannulae, whereas appetitive stimuli are given in drinking bottles. Differences in these 2 methods make comparison of taste-evoked brain activity between results that utilize these methods problematic. Surprisingly, the intraoral cannulae experimental conditions that produce a similar pattern of c-Fos activity in response to taste stimulation remain unexplored. Stimulation pattern (e.g., constant/intermittent) and hydration state (e.g., water-restricted/hydrated) are the 2 primary differences between delivering tastes via bottles versus intraoral cannulae. Thus, we quantified monosodium glutamate (MSG)-evoked brain activity, as measured by c-Fos, in the nucleus of the solitary tract (nTS; primary taste nucleus) across several conditions. The number and pattern of c-Fos neurons in the nTS of animals that were water-restricted and received a constant infusion of MSG via intraoral cannula most closely mimicked animals that consumed MSG from a bottle. Therefore, in order to compare c-Fos activity between cannulae-stimulated and bottle-stimulated animals, cannulated animals should be water restricted prior to stimulation, and receive taste stimuli at a constant flow. PMID:26762887
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Complexity and Competition in Appetitive and Aversive Neural Circuits
Barberini, Crista L.; Morrison, Sara E.; Saez, Alex; Lau, Brian; Salzman, C. Daniel
2012-01-01
Decision-making often involves using sensory cues to predict possible rewarding or punishing reinforcement outcomes before selecting a course of action. Recent work has revealed complexity in how the brain learns to predict rewards and punishments. Analysis of neural signaling during and after learning in the amygdala and orbitofrontal cortex, two brain areas that process appetitive and aversive stimuli, reveals a dynamic relationship between appetitive and aversive circuits. Specifically, the relationship between signaling in appetitive and aversive circuits in these areas shifts as a function of learning. Furthermore, although appetitive and aversive circuits may often drive opposite behaviors – approaching or avoiding reinforcement depending upon its valence – these circuits can also drive similar behaviors, such as enhanced arousal or attention; these processes also may influence choice behavior. These data highlight the formidable challenges ahead in dissecting how appetitive and aversive neural circuits interact to produce a complex and nuanced range of behaviors. PMID:23189037
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Hippocampal Processing of Ambiguity Enhances Fear Memory
Amadi, Ugwechi; Lim, Seh Hong; Liu, Elizabeth; Baratta, Michael V.; Goosens, Ki Ann
2016-01-01
Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, where dangerous situations can lead to unpleasant outcomes in unpredictable ways. Here we varied the timing of aversive events following predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of CA1 cells during aversive negative prediction errors prevented this enhancement of fear without impacting fear learning for predictable events. Dorsal hippocampal inactivation also prevented ambiguity-related enhancement of fear during auditory fear conditioning under a partial reinforcement schedule. These results reveal that information about the timing and occurrence of aversive events is rapidly acquired and that unexpectedly timed or omitted aversive events generate hippocampal signals to enhance fear learning. PMID:28182526
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Hippocampal Processing of Ambiguity Enhances Fear Memory.
Amadi, Ugwechi; Lim, Seh Hong; Liu, Elizabeth; Baratta, Michael V; Goosens, Ki A
2017-02-01
Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, in which dangerous situations can lead to unpleasant outcomes in unpredictable ways. In the current experiments, we varied the timing of aversive events after predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of cornu ammonis 1 cells during aversive negative prediction errors prevented this enhancement of fear without affecting fear learning for predictable events. Dorsal hippocampal inactivation also prevented ambiguity-related enhancement of fear during auditory fear conditioning under a partial-reinforcement schedule. These results reveal that information about the timing and occurrence of aversive events is rapidly acquired and that unexpectedly timed or omitted aversive events generate hippocampal signals to enhance fear learning.
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Sarco/Endoplasmic Reticulum Ca2+-ATPases (SERCA) Contribute to GPCR-Mediated Taste Perception
Iguchi, Naoko; Ohkuri, Tadahiro; Slack, Jay P.; Zhong, Ping; Huang, Liquan
2011-01-01
The sense of taste is important for providing animals with valuable information about the qualities of food, such as nutritional or harmful nature. Mammals, including humans, can recognize at least five primary taste qualities: sweet, umami (savory), bitter, sour, and salty. Recent studies have identified molecules and mechanisms underlying the initial steps of tastant-triggered molecular events in taste bud cells, particularly the requirement of increased cytosolic free Ca2+ concentration ([Ca2+]c) for normal taste signal transduction and transmission. Little, however, is known about the mechanisms controlling the removal of elevated [Ca2+]c from the cytosol of taste receptor cells (TRCs) and how the disruption of these mechanisms affects taste perception. To investigate the molecular mechanism of Ca2+ clearance in TRCs, we sought the molecules involved in [Ca2+]c regulation using a single-taste-cell transcriptome approach. We found that Serca3, a member of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) family that sequesters cytosolic Ca2+ into endoplasmic reticulum, is exclusively expressed in sweet/umami/bitter TRCs, which rely on intracellular Ca2+ release for signaling. Serca3-knockout (KO) mice displayed significantly increased aversive behavioral responses and greater gustatory nerve responses to bitter taste substances but not to sweet or umami taste substances. Further studies showed that Serca2 was mainly expressed in the T1R3-expressing sweet and umami TRCs, suggesting that the loss of function of Serca3 was possibly compensated by Serca2 in these TRCs in the mutant mice. Our data demonstrate that the SERCA family members play an important role in the Ca2+ clearance in TRCs and that mutation of these proteins may alter bitter and perhaps sweet and umami taste perception. PMID:21829714
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A potential sex dimorphism in the relationship between bitter taste and alcohol consumption.
Beckett, Emma Louise; Duesing, Konsta; Boyd, Lyndell; Yates, Zoe; Veysey, Martin; Lucock, Mark
2017-03-22
Bitterness is an innate aversive taste important in detecting potentially toxic substances, including alcohol. However, bitter compounds exist in many foods and beverages, and can be desirable, such as in beer. TAS2R38 is a well-studied bitter taste receptor with common polymorphisms. Some have reported relationships between TAS2R38 genotypes, bitter taste phenotype and alcohol intake, however results have been mixed. These mixed results may be explained by the varying taste properties of different alcoholic beverages or a sex dimorphism in responses. Bitter taste phenotype was assessed using PROP taste test and TAS2R38-P49A genotype was assessed by RFLP-PCR. Alcohol intake was assessed by food frequency questionnaire and classified by beverage type (beer, wine, spirits or mixed drinks). The relationships between bitter taste phenotype and carriage of the P allele of the TAS2R38-A49P gene and alcohol intake were assessed adjusted for and stratified by sex, and the interaction between taste and sex was evaluated. The relationship between alcohol intake and bitter taste phenotype varied by beverage type, with significant results for beer, spirits and mixed drinks, but not wine. When stratified, results varied by sex, and were only significant in males. Significant interactions were found for taster phenotype and sex (total alcohol intake and intake of beer and spirits). Results were similar for carriage of the TAS2R38-P49A P allele. Sex-specific interactions between bitter taste phenotype, TAS2R38 genotype and alcohol intake may explain variance in previous studies and may have implications for sex-specific disease risk and public health interventions.
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Koren, Gideon; Rieder, Michael J; Amitai, Yona
2016-01-01
Children's aversions to poor and mostly bitter tastes and their inability to swallow tablets and capsules are major challenges in pediatric medicine. Sodium phenylbutyrate (NaPB) is a lifesaving waste nitrogen, alternative to urea nitrogen, for individuals suffering from urea cycle disorders. A major issue in the use of NaPB is its highly foul taste, which often leads to children being unable to consume it, resulting in ineffective treatment, or alternatively, necessitating the application of the drug through a nasogastric tube or gastrostomy. This study reviews the published data on a novel formulation of NaPB, Pheburane ® granules, which begin to release their NaPB after a lag time of ~10 seconds followed by a slow release over several minutes. The taste-masked granule formulation of NaPB dramatically improves the acceptability of the drug by children and appears in initial studies to be both safe and effective. While more studies are needed to substantiate and enrich these initial trials, the available data provide a telling example where masking the drug taste of medicine for children can sometimes be the difference between life and death.
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Koren, Gideon; Rieder, Michael J; Amitai, Yona
2016-01-01
Background Children’s aversions to poor and mostly bitter tastes and their inability to swallow tablets and capsules are major challenges in pediatric medicine. Sodium phenylbutyrate (NaPB) is a lifesaving waste nitrogen, alternative to urea nitrogen, for individuals suffering from urea cycle disorders. A major issue in the use of NaPB is its highly foul taste, which often leads to children being unable to consume it, resulting in ineffective treatment, or alternatively, necessitating the application of the drug through a nasogastric tube or gastrostomy. Methods This study reviews the published data on a novel formulation of NaPB, Pheburane® granules, which begin to release their NaPB after a lag time of ~10 seconds followed by a slow release over several minutes. Results The taste-masked granule formulation of NaPB dramatically improves the acceptability of the drug by children and appears in initial studies to be both safe and effective. Conclusion While more studies are needed to substantiate and enrich these initial trials, the available data provide a telling example where masking the drug taste of medicine for children can sometimes be the difference between life and death. PMID:27799750
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From Cell to Beak: In-Vitro and In-Vivo Characterization of Chicken Bitter Taste Thresholds.
Cheled-Shoval, Shira; Behrens, Maik; Korb, Ayelet; Di Pizio, Antonella; Meyerhof, Wolfgang; Uni, Zehava; Niv, Masha Y
2017-05-17
Bitter taste elicits an aversive reaction, and is believed to protect against consuming poisons. Bitter molecules are detected by the Tas2r family of G-protein-coupled receptors, with a species-dependent number of subtypes. Chickens demonstrate bitter taste sensitivity despite having only three bitter taste receptors-ggTas2r1, ggTas2r2 and ggTas2r7. This minimalistic bitter taste system in chickens was used to determine relationships between in-vitro (measured in heterologous systems) and in-vivo (behavioral) detection thresholds. ggTas2r-selective ligands, nicotine (ggTas2r1), caffeine (ggTas2r2), erythromycin and (+)-catechin (ggTas2r7), and the Tas2r-promiscuous ligand quinine (all three ggTas2rs) were studied. Ligands of the same receptor had different in-vivo:in-vitro ratios, and the ggTas2r-promiscuous ligand did not exhibit lower in-vivo:in-vitro ratios than ggTas2r-selective ligands. In-vivo thresholds were similar or up to two orders of magnitude higher than the in-vitro ones.
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Boundary Conditions for the Maintenance of Memory by PKM[zeta] in Neocortex
ERIC Educational Resources Information Center
Shema, Reul; Hazvi, Shoshi; Sacktor, Todd C.; Dudai, Yadin
2009-01-01
We report here that ZIP, a selective inhibitor of the atypical protein kinase C isoform PKM[zeta], abolishes very long-term conditioned taste aversion (CTA) associations in the insular cortex of the behaving rat, at least 3 mo after encoding. The effect of ZIP is not replicated by a general serine/threonine protein kinase inhibitor that is…
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ERIC Educational Resources Information Center
Osorio-Gómez, Daniel; Guzmán-Ramos, Kioko; Bermúdez-Rattoni, Federico
2017-01-01
The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the…
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ERIC Educational Resources Information Center
Friman, Patrick C.; Hove, Gayleen
1987-01-01
The study examined effects of aversive taste treatment of thumb sucking on untreated habitual hair pulling by two young males (ages 2 and 5). Concomitant with successful treatment of thumb sucking, hair pulling was also eliminated. Results suggest an efficient method for changing behaviors that are difficult to treat directly. (Author/JW)
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Overcoming Learning Aversion in Evaluating and Managing Uncertain Risks.
Cox, Louis Anthony Tony
2015-10-01
Decision biases can distort cost-benefit evaluations of uncertain risks, leading to risk management policy decisions with predictably high retrospective regret. We argue that well-documented decision biases encourage learning aversion, or predictably suboptimal learning and premature decision making in the face of high uncertainty about the costs, risks, and benefits of proposed changes. Biases such as narrow framing, overconfidence, confirmation bias, optimism bias, ambiguity aversion, and hyperbolic discounting of the immediate costs and delayed benefits of learning, contribute to deficient individual and group learning, avoidance of information seeking, underestimation of the value of further information, and hence needlessly inaccurate risk-cost-benefit estimates and suboptimal risk management decisions. In practice, such biases can create predictable regret in selection of potential risk-reducing regulations. Low-regret learning strategies based on computational reinforcement learning models can potentially overcome some of these suboptimal decision processes by replacing aversion to uncertain probabilities with actions calculated to balance exploration (deliberate experimentation and uncertainty reduction) and exploitation (taking actions to maximize the sum of expected immediate reward, expected discounted future reward, and value of information). We discuss the proposed framework for understanding and overcoming learning aversion and for implementing low-regret learning strategies using regulation of air pollutants with uncertain health effects as an example. © 2015 Society for Risk Analysis.
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Sitaraman, Divya; Kramer, Elizabeth F.; Kahsai, Lily; Ostrowski, Daniela; Zars, Troy
2017-01-01
Feedback mechanisms in operant learning are critical for animals to increase reward or reduce punishment. However, not all conditions have a behavior that can readily resolve an event. Animals must then try out different behaviors to better their situation through outcome learning. This form of learning allows for novel solutions and with positive experience can lead to unexpected behavioral routines. Learned helplessness, as a type of outcome learning, manifests in part as increases in escape latency in the face of repeated unpredicted shocks. Little is known about the mechanisms of outcome learning. When fruit fly Drosophila melanogaster are exposed to unpredicted high temperatures in a place learning paradigm, flies both increase escape latencies and have a higher memory when given control of a place/temperature contingency. Here we describe discrete serotonin neuronal circuits that mediate aversive reinforcement, escape latencies, and memory levels after place learning in the presence and absence of unexpected aversive events. The results show that two features of learned helplessness depend on the same modulatory system as aversive reinforcement. Moreover, changes in aversive reinforcement and escape latency depend on local neural circuit modulation, while memory enhancement requires larger modulation of multiple behavioral control circuits. PMID:29321732
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Walker, Ellen A
2010-01-01
As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.
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Flood-conditioned place aversion as a novel non-pharmacological aversive learning procedure in mice.
Goltseker, Koral; Barak, Segev
2018-05-08
The place conditioning paradigm is an efficient, widely-used method to study mechanisms that underlie appetitive or aversive learning and memory processes. However, pharmacological agents used to induce conditioned place preference (CPP) or aversion (CPA) can per se interfere with learning and memory processing, hence confounding the results. Therefore, non-pharmacological place conditioning procedures are of high importance. Here, we introduce a novel procedure for induction of CPA in mice, by water flooding. We found that pairing a context with immersion in moderately cold shallow water resulted in aversion and avoidance of that context during a place preference test. Importantly, place aversion emerged only when mice experienced the onset of flood during conditioning training, but not when mice were placed in a compartment pre-filled with water. We also found that warm water was not sufficiently aversive to induce CPA. Moreover, CPA was observed after two or three context-flood pairings but not after one or four pairings, suggesting that moderate conditioning intensity produces optimal CPA expression. Thus, flood-induced CPA is a simple, cheap, and efficient procedure to form and measure place aversion memories in mice, using an ethologically-relevant threat.
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King, Michael S
2018-03-15
The location of neurons in the gustatory cortex (GC) activated by intra-oral infusion of solutions in conscious rats was mapped using Fos immunohistochemistry. Groups of adult male Wistar rats (N's = 5) received an infusion of one of the following: dH 2 O, 0.1 or 1.0 M NaCl, 0.1 or 1.0 M sucrose, 0.32 M MSG (with 100 µM amiloride and 2.5 M inosine 5'-monophosphate), 0.03 M HCl, or 0.003 M QHCl delivered via an intra-oral cannula (0.233 ml/min for 5 min). Unstimulated control rats received no infusion. Taste reactivity (TR) behaviors were videotaped and scored. The number of Fos-immunoreactive (Fos-IR) neurons was counted in eight sections throughout the anterior-posterior extent of the GC in the medial and lateral halves of the granular (GI), dysgranular (DI), and dorsal (AID) and ventral (AIV) agranular insular cortices. Intra-oral infusion of dH 2 O, NaCl, or sucrose altered the number of Fos-IR neurons in only specific subareas of the GC and the effects of these tastants were concentration-dependent. For example, 1.0 M NaCl increased Fos-IR neurons in the posterior lateral AID and DI and elicited more aversive TR responses than 0.1 M NaCl. Compared to dH 2 O, infusions of HCl or QHCl increased the total number of Fos-IR neurons in many subareas of the GC throughout its anterior-posterior extent and increased aversive TR behaviors. Linear regression analyses suggested that neurons in the medial AID of the posterior GC may influence aversive behavioral responses to HCl and QHCl while neurons in the posterior lateral AID and DI may play a role in aversive TR responses to 1.0 M NaCl. Copyright © 2018 Elsevier B.V. All rights reserved.
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Prepared stimuli enhance aversive learning without weakening the impact of verbal instructions
2018-01-01
Fear-relevant stimuli such as snakes and spiders are thought to capture attention due to evolutionary significance. Classical conditioning experiments indicate that these stimuli accelerate learning, while instructed extinction experiments suggest they may be less responsive to instructions. We manipulated stimulus type during instructed aversive reversal learning and used quantitative modeling to simultaneously test both hypotheses. Skin conductance reversed immediately upon instruction in both groups. However, fear-relevant stimuli enhanced dynamic learning, as measured by higher learning rates in participants conditioned with images of snakes and spiders. Results are consistent with findings that dissociable neural pathways underlie feedback-driven and instructed aversive learning. PMID:29339561
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Examinations of the reward comparison hypothesis: The modulation of gender and footshock.
Huang, Andrew Chih Wei; Wang, Cheng Chung; Wang, Shiun
2015-11-01
The reward comparison hypothesis suggests that drugs of abuse-induced conditioned saccharin suppression intake is due to the reward value of drugs of abuse that outweighs that of a saccharin solution dissociating from the aversive LiCl-induced conditioned taste aversion (CTA). Huang and Hsiao (2008) provided some conflict data to challenge the reward comparison hypothesis. Whether the rewarding drugs of abuse-induced conditioned suppression and the aversive LiCl-induced CTA resulted from aversion or reward should be addressed. The present study investigated how gender and footshock affect aversive LiCl- and rewarding morphine- and methamphetamine (MAMPH)-induced conditioned suppression to re-examine the reward comparison hypothesis. The results indicated that gender and footshock did not directly influence the aversive LiCl-induced CTA or rewarding morphine- and MAMPH-induced conditioned suppression. The gender effect interacted with the drug effect in the aversive LiCl- and rewarding MAMPH-induced conditioned suppression but did not interact with the drug effect in the rewarding morphine-induced conditioned suppression. Footshock interacted with the drug effect in rewarding morphine- and MAMPH-induced conditioned suppression, but footshock did not interact with the drug effect in the aversive LiCl-induced CTA. Therefore, the gender and footshock effects might play a modulatory (but not a mediating) role with the drug effect. The present data indicated that footshock modulates drugs of abuse-induced conditioned suppression, which is consistent with the reward comparison hypothesis, but our findings with regard to the modulatory role of the gender effect and the drug effect do not support this hypothesis. The reward comparison hypothesis should be discussed and possibly reconsidered. Copyright © 2015. Published by Elsevier Inc.
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Encoding of aversion by dopamine and the nucleus accumbens.
McCutcheon, James E; Ebner, Stephanie R; Loriaux, Amy L; Roitman, Mitchell F
2012-01-01
Adaptive motivated behavior requires rapid discrimination between beneficial and harmful stimuli. Such discrimination leads to the generation of either an approach or rejection response, as appropriate, and enables organisms to maximize reward and minimize punishment. Classically, the nucleus accumbens (NAc) and the dopamine projection to it are considered an integral part of the brain's reward circuit, i.e., they direct approach and consumption behaviors and underlie positive reinforcement. This reward-centered framing ignores important evidence about the role of this system in encoding aversive events. One reason for bias toward reward is the difficulty in designing experiments in which animals repeatedly experience punishments; another is the challenge in dissociating the response to an aversive stimulus itself from the reward/relief experienced when an aversive stimulus is terminated. Here, we review studies that employ techniques with sufficient time resolution to measure responses in ventral tegmental area and NAc to aversive stimuli as they are delivered. We also present novel findings showing that the same stimulus - intra-oral infusion of sucrose - has differing effects on NAc shell dopamine release depending on the prior experience. Here, for some rats, sucrose was rendered aversive by explicitly pairing it with malaise in a conditioned taste aversion paradigm. Thereafter, sucrose infusions led to a suppression of dopamine with a similar magnitude and time course to intra-oral infusions of a bitter quinine solution. The results are discussed in the context of regional differences in dopamine signaling and the implications of a pause in phasic dopamine release within the NAc shell. Together with our data, the emerging literature suggests an important role for differential phasic dopamine signaling in aversion vs. reward.
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A high-throughput method to measure NaCl and acid taste thresholds in mice.
Ishiwatari, Yutaka; Bachmanov, Alexander A
2009-05-01
To develop a technique suitable for measuring NaCl taste thresholds in genetic studies, we conducted a series of experiments with outbred CD-1 mice using conditioned taste aversion (CTA) and two-bottle preference tests. In Experiment 1, we compared conditioning procedures involving either oral self-administration of LiCl or pairing NaCl intake with LiCl injections and found that thresholds were the lowest after LiCl self-administration. In Experiment 2, we compared different procedures (30-min and 48-h tests) for testing conditioned mice and found that the 48-h test is more sensitive. In Experiment 3, we examined the effects of varying strength of conditioned (NaCl or LiCl taste intensity) and unconditioned (LiCl toxicity) stimuli and concluded that 75-150 mM LiCl or its mixtures with NaCl are the optimal stimuli for conditioning by oral self-administration. In Experiment 4, we examined whether this technique is applicable for measuring taste thresholds for other taste stimuli. Results of these experiments show that conditioning by oral self-administration of LiCl solutions or its mixtures with other taste stimuli followed by 48-h two-bottle tests of concentration series of a conditioned stimulus is an efficient and sensitive method to measure taste thresholds. Thresholds measured with this technique were 2 mM for NaCl and 1 mM for citric acid. This approach is suitable for simultaneous testing of large numbers of animals, which is required for genetic studies. These data demonstrate that mice, like several other species, generalize CTA from LiCl to NaCl, suggesting that they perceive taste of NaCl and LiCl as qualitatively similar, and they also can generalize CTA of a binary mixture of taste stimuli to mixture components.
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Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism.
Fan, Lu; Balakrishna, Shrilatha; Jabba, Sairam V; Bonner, Pamela E; Taylor, Seth R; Picciotto, Marina R; Jordt, Sven-Eric
2016-11-01
Nicotine is a major oral irritant in smokeless tobacco products and has an aversive taste. Mentholated smokeless tobacco products are highly popular, suggesting that menthol increases their palatability and may facilitate initiation of product use. While menthol is known to reduce respiratory irritation by tobacco smoke irritants, it is not known whether this activity extends to oral nicotine and its aversive effects. The two-bottle choice drinking assay was used to characterise aversion and preference in C57BL/6 mice to a range of menthol concentrations (10-200 µg/mL). Then, effects of menthol on oral nicotine aversion were determined. Responses were compared with those in mice deficient in the cold/menthol receptor, TRPM8, expressed in trigeminal sensory neurons innervating the oral cavity. Mice showed aversion to menthol concentrations of 100 µg/mL and above. When presented with a highly aversive concentration of nicotine (200 µg/mL), mice preferred solutions with 50 or 100 µg/mL menthol added over nicotine alone. In contrast to wild-type mice, Trpm8-/- showed a strong aversion to mentholated (100 µg/mL) nicotine (200 µg/mL) and preferred nicotine alone. Trpm8-/- mice show aversion to lower concentrations of menthol than wild-type mice. Oral menthol can reduce the aversive effects of oral nicotine and, at higher concentrations, acts as an irritant by itself. Menthol's effects in relation to nicotine require TRPM8, the cool temperature sensing ion channel that activates analgesic and counterirritant mechanisms. These mechanisms may underlie preference for menthol-containing smokeless tobacco products and may facilitate initiation of product use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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Tudge, Luke; Williams, Clare; Cowen, Philip J.
2015-01-01
Background: Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders. We previously showed that the cannabis receptor subtype (CB1) inverse agonist rimonabant, an antiobesity drug withdrawn due to depressogenic side effects, diminished neural reward responses yet increased aversive responses (Horder et al., 2010). Unlike rimonabant, tetrahydrocannabivarin is a neutral CB1 receptor antagonist (Pertwee, 2005) and may therefore produce different modulations of the neural reward system. We hypothesized that tetrahydrocannabivarin would, unlike rimonabant, leave intact neural reward responses but augment aversive responses. Methods: We used a within-subject, double-blind design. Twenty healthy volunteers received a single dose of tetrahydrocannabivarin (10mg) and placebo in randomized order on 2 separate occasions. We measured the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (picture of moldy strawberries and/or a less pleasant strawberry taste) using functional magnetic resonance imaging. Volunteers rated pleasantness, intensity, and wanting for each stimulus. Results: There were no significant differences between groups in subjective ratings. However, tetrahydrocannabivarin increased responses to chocolate stimuli in the midbrain, anterior cingulate cortex, caudate, and putamen. Tetrahydrocannabivarin also increased responses to aversive stimuli in the amygdala, insula, mid orbitofrontal cortex, caudate, and putamen. Conclusions: Our findings are the first to show that treatment with the CB1 neutral antagonist tetrahydrocannabivarin increases neural responding to rewarding and aversive stimuli. This effect profile suggests therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects. PMID:25542687
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Tudge, Luke; Williams, Clare; Cowen, Philip J; McCabe, Ciara
2014-12-25
Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders. We previously showed that the cannabis receptor subtype (CB1) inverse agonist rimonabant, an antiobesity drug withdrawn due to depressogenic side effects, diminished neural reward responses yet increased aversive responses (Horder et al., 2010). Unlike rimonabant, tetrahydrocannabivarin is a neutral CB1 receptor antagonist (Pertwee, 2005) and may therefore produce different modulations of the neural reward system. We hypothesized that tetrahydrocannabivarin would, unlike rimonabant, leave intact neural reward responses but augment aversive responses. We used a within-subject, double-blind design. Twenty healthy volunteers received a single dose of tetrahydrocannabivarin (10mg) and placebo in randomized order on 2 separate occasions. We measured the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (picture of moldy strawberries and/or a less pleasant strawberry taste) using functional magnetic resonance imaging. Volunteers rated pleasantness, intensity, and wanting for each stimulus. There were no significant differences between groups in subjective ratings. However, tetrahydrocannabivarin increased responses to chocolate stimuli in the midbrain, anterior cingulate cortex, caudate, and putamen. Tetrahydrocannabivarin also increased responses to aversive stimuli in the amygdala, insula, mid orbitofrontal cortex, caudate, and putamen. Our findings are the first to show that treatment with the CB1 neutral antagonist tetrahydrocannabivarin increases neural responding to rewarding and aversive stimuli. This effect profile suggests therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects. © The Author 2015. Published by Oxford University Press on behalf of CINP.
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Awata, Hiroko; Watanabe, Takahito; Hamanaka, Yoshitaka; Mito, Taro; Noji, Sumihare; Mizunami, Makoto
2015-11-02
Elucidation of reinforcement mechanisms in associative learning is an important subject in neuroscience. In mammals, dopamine neurons are thought to play critical roles in mediating both appetitive and aversive reinforcement. Our pharmacological studies suggested that octopamine and dopamine neurons mediate reward and punishment, respectively, in crickets, but recent studies in fruit-flies concluded that dopamine neurons mediates both reward and punishment, via the type 1 dopamine receptor Dop1. To resolve the discrepancy between studies in different insect species, we produced Dop1 knockout crickets using the CRISPR/Cas9 system and found that they are defective in aversive learning with sodium chloride punishment but not appetitive learning with water or sucrose reward. The results suggest that dopamine and octopamine neurons mediate aversive and appetitive reinforcement, respectively, in crickets. We suggest unexpected diversity in neurotransmitters mediating appetitive reinforcement between crickets and fruit-flies, although the neurotransmitter mediating aversive reinforcement is conserved. This study demonstrates usefulness of the CRISPR/Cas9 system for producing knockout animals for the study of learning and memory.
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Drosophila Learn Opposing Components of a Compound Food Stimulus
Das, Gaurav; Klappenbach, Martín; Vrontou, Eleftheria; Perisse, Emmanuel; Clark, Christopher M.; Burke, Christopher J.; Waddell, Scott
2014-01-01
Summary Dopaminergic neurons provide value signals in mammals and insects [1–3]. During Drosophila olfactory learning, distinct subsets of dopaminergic neurons appear to assign either positive or negative value to odor representations in mushroom body neurons [4–9]. However, it is not known how flies evaluate substances that have mixed valence. Here we show that flies form short-lived aversive olfactory memories when trained with odors and sugars that are contaminated with the common insect repellent DEET. This DEET-aversive learning required the MB-MP1 dopaminergic neurons that are also required for shock learning [7]. Moreover, differential conditioning with DEET versus shock suggests that formation of these distinct aversive olfactory memories relies on a common negatively reinforcing dopaminergic mechanism. Surprisingly, as time passed after training, the behavior of DEET-sugar-trained flies reversed from conditioned odor avoidance into odor approach. In addition, flies that were compromised for reward learning exhibited a more robust and longer-lived aversive-DEET memory. These data demonstrate that flies independently process the DEET and sugar components to form parallel aversive and appetitive olfactory memories, with distinct kinetics, that compete to guide learned behavior. PMID:25042590
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Cue-elicited food seeking is eliminated with aversive outcomes following outcome devaluation.
Eder, Andreas B; Dignath, David
2016-01-01
In outcome-selective Pavlovian-to-instrumental transfer (PIT), stimuli that are predictive of specific outcomes prime instrumental responses that are associated with these outcomes. Previous human studies yielded mixed evidence in respect to whether the PIT effect is affected by a posttraining devaluation of an outcome, with the PIT effect being preserved after a devaluation of a primary reinforcer (food, drugs) but not following the devaluation of a secondary reinforcer (money). The present research examined whether outcome-selective transfer is eliminated when the devaluation of a primary (liquid) reinforcer is strong and aversive. Experiment 1 confirmed these expectations following a devaluation with bad tasting Tween 20. However, outcome-selective transfer was still observed when the earned (devalued) outcome was not consumed immediately after each test (Experiment 2). These results suggest that the capacity of a Pavlovian cue to motivate a specific response is affected by the incentive value of the shared outcome only when the devaluation yields an aversive outcome that is consumed immediately.
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Stratford, Jennifer M; Thompson, John A
2016-03-01
The marker of neuronal activation, c-Fos, can be used to visualize spatial patterns of neural activity in response to taste stimulation. Because animals will not voluntarily consume aversive tastes, these stimuli are infused directly into the oral cavity via intraoral cannulae, whereas appetitive stimuli are given in drinking bottles. Differences in these 2 methods make comparison of taste-evoked brain activity between results that utilize these methods problematic. Surprisingly, the intraoral cannulae experimental conditions that produce a similar pattern of c-Fos activity in response to taste stimulation remain unexplored. Stimulation pattern (e.g., constant/intermittent) and hydration state (e.g., water-restricted/hydrated) are the 2 primary differences between delivering tastes via bottles versus intraoral cannulae. Thus, we quantified monosodium glutamate (MSG)-evoked brain activity, as measured by c-Fos, in the nucleus of the solitary tract (nTS; primary taste nucleus) across several conditions. The number and pattern of c-Fos neurons in the nTS of animals that were water-restricted and received a constant infusion of MSG via intraoral cannula most closely mimicked animals that consumed MSG from a bottle. Therefore, in order to compare c-Fos activity between cannulae-stimulated and bottle-stimulated animals, cannulated animals should be water restricted prior to stimulation, and receive taste stimuli at a constant flow. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Tauber, John M; Brown, Elizabeth B; Li, Yuanyuan; Yurgel, Maria E; Masek, Pavel; Keene, Alex C
2017-11-01
Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass. The highly palatable taste of free fatty acids (FAs), one of the building blocks of fat, promotes food consumption, activates reward circuitry, and is thought to contribute to hedonic feeding underlying many metabolism-related disorders. Despite a role in the etiology of metabolic diseases, little is known about how dietary fats are detected by the gustatory system to promote feeding. Previously, we showed that a broad population of sugar-sensing taste neurons expressing Gustatory Receptor 64f (Gr64f) is required for reflexive feeding responses to both FAs and sugars. Here, we report a genetic silencing screen to identify specific populations of taste neurons that mediate fatty acid (FA) taste. We find neurons identified by expression of Ionotropic Receptor 56d (IR56d) are necessary and sufficient for reflexive feeding response to FAs. Functional imaging reveals that IR56d-expressing neurons are responsive to short- and medium-chain FAs. Silencing IR56d neurons selectively abolishes FA taste, and their activation is sufficient to drive feeding responses. Analysis of co-expression with Gr64f identifies two subpopulations of IR56d-expressing neurons. While physiological imaging reveals that both populations are responsive to FAs, IR56d/Gr64f neurons are activated by medium-chain FAs and are sufficient for reflexive feeding response to FAs. Moreover, flies can discriminate between sugar and FAs in an aversive taste memory assay, indicating that FA taste is a unique modality in Drosophila. Taken together, these findings localize FA taste within the Drosophila gustatory center and provide an opportunity to investigate discrimination between different categories of appetitive tastants.
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Adachi, Ryota; Sasaki, Yuko; Morita, Hiromi; Komai, Michio; Shirakawa, Hitoshi; Goto, Tomoko; Furuyama, Akira; Isono, Kunio
2012-06-01
Transgenic Drosophila expressing human T2R4 and T2R38 bitter-taste receptors or PKD2L1 sour-taste receptor in the fly gustatory receptor neurons and other tissues were prepared using conventional Gal4/UAS binary system. Molecular analysis showed that the transgene mRNAs are expressed according to the tissue specificity of the Gal4 drivers. Transformants expressing the transgene taste receptors in the fly taste neurons were then studied by a behavioral assay to analyze whether transgene chemoreceptors are functional and coupled to the cell response. Since wild-type flies show strong aversion against the T2R ligands as in mammals, the authors analyzed the transformants where the transgenes are expressed in the fly sugar receptor neurons so that they promote feeding ligand-dependently if they are functional and activate the neurons. Although the feeding preference varied considerably among different strains and individuals, statistical analysis using large numbers of transformants indicated that transformants expressing T2R4 showed a small but significant increase in the preference for denatonium and quinine, the T2R4 ligands, as compared to the control flies, whereas transformants expressing T2R38 did not. Similarly, transformants expressing T2R38 and PKD2L1 also showed a similar preference increase for T2R38-specific ligand phenylthiocarbamide (PTC) and a sour-taste ligand, citric acid, respectively. Taken together, the transformants expressing mammalian taste receptors showed a small but significant increase in the feeding preference that is taste receptor and also ligand dependent. Although future improvements are required to attain performance comparable to the endogenous robust response, Drosophila taste neurons may serve as a potential in vivo heterologous expression system for analyzing chemoreceptor function.
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Thaker, Maria; Vanak, Abi T; Lima, Steven L; Hews, Diana K
2010-01-01
Elevated plasma corticosterone during stressful events is linked to rapid changes in behavior in vertebrates and can mediate learning and memory consolidation. We tested the importance of acute corticosterone elevation in aversive learning of a novel stressor by wild male eastern fence lizards (Sceloporus undulatus). We found that inhibiting corticosterone elevation (using metyrapone, a corticosterone synthesis blocker) during an encounter with a novel attacker impaired immediate escape responses and limited learning and recall during future encounters. In the wild and in outdoor enclosures, lizards whose acute corticosterone response was blocked by an earlier metyrapone injection did not alter their escape behavior during repeated encounters with the attacker. Control-injected (unblocked) lizards, however, progressively increased flight initiation distance and decreased hiding duration during subsequent encounters. Aversive responses were also initially higher for control lizards exposed to a higher intensity first attack. Further, we demonstrate a role of corticosterone elevation in recollection, since unblocked lizards had heightened antipredator responses 24-28 h later. Exogenously restoring corticosterone levels in metyrapone-injected lizards maintained aversive behaviors and learning at control (unblocked) levels. We suggest that the corticosterone mediation of antipredator behaviors and aversive learning is a critical and general mechanism for the behavioral flexibility of vertebrate prey.
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Learned Helplessness at Fifty: Insights from Neuroscience
Maier, Steven F.; Seligman, Martin E. P.
2016-01-01
Learned helplessness, the failure to escape shock induced by uncontrollable aversive events, was discovered half a century ago. Seligman and Maier (1967) theorized that animals learned that outcomes were independent of their responses—that nothing they did mattered – and that this learning undermined trying to escape. The mechanism of learned helplessness is now very well-charted biologically and the original theory got it backwards. Passivity in response to shock is not learned. It is the default, unlearned response to prolonged aversive events and it is mediated by the serotonergic activity of the dorsal raphe nucleus, which in turn inhibits escape. This passivity can be overcome by learning control, with the activity of the medial prefrontal cortex, which subserves the detection of control leading to the automatic inhibition of the dorsal raphe nucleus. So animals learn that they can control aversive events, but the passive failure to learn to escape is an unlearned reaction to prolonged aversive stimulation. In addition, alterations of the ventromedial prefrontal cortex-dorsal raphe pathway can come to subserve the expectation of control. We speculate that default passivity and the compensating detection and expectation of control may have substantial implications for how to treat depression. PMID:27337390
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Learned helplessness at fifty: Insights from neuroscience.
Maier, Steven F; Seligman, Martin E P
2016-07-01
Learned helplessness, the failure to escape shock induced by uncontrollable aversive events, was discovered half a century ago. Seligman and Maier (1967) theorized that animals learned that outcomes were independent of their responses-that nothing they did mattered-and that this learning undermined trying to escape. The mechanism of learned helplessness is now very well-charted biologically, and the original theory got it backward. Passivity in response to shock is not learned. It is the default, unlearned response to prolonged aversive events and it is mediated by the serotonergic activity of the dorsal raphe nucleus, which in turn inhibits escape. This passivity can be overcome by learning control, with the activity of the medial prefrontal cortex, which subserves the detection of control leading to the automatic inhibition of the dorsal raphe nucleus. So animals learn that they can control aversive events, but the passive failure to learn to escape is an unlearned reaction to prolonged aversive stimulation. In addition, alterations of the ventromedial prefrontal cortex-dorsal raphe pathway can come to subserve the expectation of control. We speculate that default passivity and the compensating detection and expectation of control may have substantial implications for how to treat depression. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
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Radiation: Behavioral Implications in Space
1988-01-01
central nervous system (CNS). Thus, because of the uncertainties bout proton and HZE radiation, the CNS and behavioral effects of these radiations should...central nervous system or with an indirect measure of emesis (conditioned taste aversion) may occur as low as 0.1 -0.25 Gy. 305 (3) Radiation effects ...paper: (1) space radiations are more effective at disrupting behavior; (2) task demands can aggravate the radiation-disruption; (3) efforts to mitigate
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Avoidance of selenium-treated food by mallards
Heinz, G.H.; Sanderson, C.J.
1990-01-01
Adult, male mallards (Anas platyrhynchos) were given a choice between a control diet and a diet containing 5, 10 or 20 ppm selenium as selenomethionine dissolved in water and mixed into the diet. At 10 and 20 ppm, selenium-treated diets were avoided. Avoidance appeared to be caused by a conditioned response, probably to illness caused by the selenium and not to an aversion to the taste of the selenium.
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Pre-exposure to wheel running disrupts taste aversion conditioning.
Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C
2002-05-01
When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.
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Blednov, Y.A.; Benavidez, J.M.; Black, M.; Chandra, D.; Homanics, G.E.; Rudolph, U.; Harris, R.A.
2012-01-01
GABA type A receptors (GABAA-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABAA-R subunits (α1, α2, α3, α4, α5 and δ). Only mice lacking the α2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the α2-subunit (Blednov et al., 2011) and indicate this aversive property of ethanol is dependent on ethanol action on α2-containing GABAA-R. Deletion of the α2-subunit led to faster recovery whereas absence of the α3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the α2 and α3 null mutants were found for flurazepam motor-incoordination. However, no differences in recovery were found in motor-incoordinating effects of an α1-selective modulator (zolpidem) or an α4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABAA-R subunits: α2 and α3. For motor activity, α3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both α2 and α3 (-/-) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing α2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the α2 subunit with human alcoholism. PMID:23147414
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Developmental emergence of fear/threat learning: neurobiology, associations and timing
Tallot, L.; Doyère, V.; Sullivan, R. M.
2016-01-01
Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive properties through pairing with an aversive stimulus, has been an important tool for exploring the neurobiology of learning. In the past decades, this neurobehavioral approach has been expanded to include the developing infant. Indeed, protracted postnatal brain development permits the exploration of how incorporating the amygdala, prefrontal cortex and hippocampus into this learning system impacts the acquisition and expression of aversive conditioning. Here, we review the developmental trajectory of these key brain areas involved in aversive conditioning and relate it to pups’ transition to independence through weaning. Overall, the data suggests that adult-like features of threat learning emerge as the relevant brain areas become incorporated into this learning. Specifically, the developmental emergence of the amygdala permits cue learning and the emergence of the hippocampus permits context learning. We also describe unique features of learning in early life that block threat learning and enhance interaction with the mother or exploration of the environment. Finally, we describe the development of a sense of time within this learning and its involvement in creating associations. Together these data suggest that the development of threat learning is a useful tool for dissecting adult-like functioning of brain circuits, as well as providing unique insights into ecologically relevant developmental changes. PMID:26534899
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Villain, Hélène; Benkahoul, Aïcha; Drougard, Anne; Lafragette, Marie; Muzotte, Elodie; Pech, Stéphane; Bui, Eric; Brunet, Alain; Birmes, Philippe; Roullet, Pascal
2016-01-01
Memory reconsolidation impairment using the β-noradrenergic receptor blocker propranolol is a promising novel treatment avenue for patients suffering from pathogenic memories, such as post-traumatic stress disorder (PTSD). However, in order to better inform targeted treatment development, the effects of this compound on memory need to be better characterized via translational research. We examined the effects of systemic propranolol administration in mice undergoing a wide range of behavioral tests to determine more specifically which aspects of the memory consolidation and reconsolidation are impaired by propranolol. We found that propranolol (10 mg/kg) affected memory consolidation in non-aversive tasks (object recognition and object location) but not in moderately (Morris water maze (MWM) to highly (passive avoidance, conditioned taste aversion) aversive tasks. Further, propranolol impaired memory reconsolidation in the most and in the least aversive tasks, but not in the moderately aversive task, suggesting its amnesic effect was not related to task aversion. Moreover, in aquatic object recognition and location tasks in which animals were forced to behave (contrary to the classic versions of the tasks); propranolol did not impair memory reconsolidation. Taken together our results suggest that the memory impairment observed after propranolol administration may result from a modification of the emotional valence of the memory rather than a disruption of the contextual component of the memory trace. This is relevant to the use of propranolol to block memory reconsolidation in individuals with PTSD, as such a treatment would not erase the traumatic memory but only reduce the emotional valence associated with this event. PMID:27014009
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Ethanol-related behaviors in mice lacking the sigma-1 receptor.
Valenza, Marta; DiLeo, Alyssa; Steardo, Luca; Cottone, Pietro; Sabino, Valentina
2016-01-15
The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulant addiction; however, fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3-20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was instead unaltered in the mutants. Our results prove that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol. Copyright © 2015 Elsevier B.V. All rights reserved.
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Ethanol-related behaviors in mice lacking the sigma-1 receptor
Valenza, Marta; DiLeo, Alyssa; Steardo, Luca; Cottone, Pietro; Sabino, Valentina
2015-01-01
Rationale The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulants addiction, but fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. Objectives The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. Methods We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3%–20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Results Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was unaltered in the mutants. Conclusions Our results suggest that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol. PMID:26462569
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The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14.
Levit, Anat; Nowak, Stefanie; Peters, Maximilian; Wiener, Ayana; Meyerhof, Wolfgang; Behrens, Maik; Niv, Masha Y
2014-03-01
Bitter taste receptors (TAS2Rs) mediate aversive response to toxic food, which is often bitter. These G-protein-coupled receptors are also expressed in extraoral tissues, and emerge as novel targets for therapeutic indications such as asthma and infection. Our goal was to identify ligands of the broadly tuned TAS2R14 among clinical drugs. Molecular properties of known human bitter taste receptor TAS2R14 agonists were incorporated into pharmacophore- and shape-based models and used to computationally predict additional ligands. Predictions were tested by calcium imaging of TAS2R14-transfected HEK293 cells. In vitro testing of the virtual screening predictions resulted in 30-80% success rates, and 15 clinical drugs were found to activate the TAS2R14. hERG potassium channel, which is predominantly expressed in the heart, emerged as a common off-target of bitter drugs. Despite immense chemical diversity of known TAS2R14 ligands, novel ligands and previously unknown polypharmacology of drugs were unraveled by in vitro screening of computational predictions. This enables rational repurposing of traditional and standard drugs for bitter taste signaling modulation for therapeutic indications.
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The strength of aversive and appetitive associations and maladaptive behaviors.
Itzhak, Yossef; Perez-Lanza, Daniel; Liddie, Shervin
2014-08-01
Certain maladaptive behaviors are thought to be acquired through classical Pavlovian conditioning. Exaggerated fear response, which can develop through Pavlovian conditioning, is associated with acquired anxiety disorders such as post-traumatic stress disorders (PTSDs). Inflated reward-seeking behavior, which develops through Pavlovian conditioning, underlies some types of addictive behavior (e.g., addiction to drugs, food, and gambling). These maladaptive behaviors are dependent on associative learning and the development of long-term memory (LTM). In animal models, an aversive reinforcer (fear conditioning) encodes an aversive contextual and cued LTM. On the other hand, an appetitive reinforcer results in conditioned place preference (CPP) that encodes an appetitive contextual LTM. The literature on weak and strong associative learning pertaining to the development of aversive and appetitive LTM is relatively scarce; thus, this review is particularly focused on the strength of associative learning. The strength of associative learning is dependent on the valence of the reinforcer and the salience of the conditioned stimulus that ultimately sways the strength of the memory trace. Our studies suggest that labile (weak) aversive and appetitive LTM may share similar signaling pathways, whereas stable (strong) aversive and appetitive LTM is mediated through different pathways. In addition, we provide some evidence suggesting that extinction of aversive fear memory and appetitive drug memory is likely to be mediated through different signaling molecules. We put forward the importance of studies aimed to investigate the molecular mechanisms underlying the development of weak and strong memories (aversive and appetitive), which would ultimately help in the development of targeted pharmacotherapies for the management of maladaptive behaviors that arise from classical Pavlovian conditioning. © 2014 International Union of Biochemistry and Molecular Biology.
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Ieki, Takashi; Okada, Shinji; Aihara, Yoshiko; Ohmoto, Makoto; Abe, Keiko; Yasuoka, Akihito; Misaka, Takumi
2013-06-01
The sense of taste plays a pivotal role in the food-selecting behaviors of vertebrates. We have shown that the fish ortholog of the phospholipase C gene (plc-β2) is expressed in a subpopulation of taste bud cells that transmit taste stimuli to the central nervous system to evoke favorable and aversive behaviors. We generated transgenic medaka expressing wheat germ agglutinin (WGA) under the control of a regulatory region of the medaka plc-β2 gene to analyze the neuronal circuit connected to these sensory cells. Immunohistochemical analysis of the transgenic fish 12 days post fertilization revealed that the WGA protein was transferred to cranial sensory ganglia and several nuclei in the hindbrain. WGA signals were also detected in the secondary gustatory nucleus in the hindbrain of 3-month-old transgenic fish. WGA signals were observed in several diencephalic and telencephalic regions in 9-month-old transgenic fish. The age-dependent increase in the labeled brain regions strongly suggests that labeling occurred at taste bud cells and progressively extended to cranial nerves and neurons in the central nervous system. These data are the first to demonstrate the tracing of higher order gustatory neuronal circuitry that is associated with a specific subpopulation of taste bud cells. These results provide insight into the basic neuronal architecture of gustatory information processing that is common among vertebrates. Copyright © 2012 Wiley Periodicals, Inc.
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Stress, κ manipulations, and aversive effects of ethanol in adolescent and adult male rats.
Anderson, R I; Agoglia, A E; Morales, M; Varlinskaya, E I; Spear, L P
2013-09-26
Elevated ethanol use during adolescence, a potentially stressful developmental period, is accompanied by insensitivity to many aversive effects of ethanol relative to adults. Given evidence that supports a role for stress and the kappa opioid receptor (KOR) system in mediating aversive properties of ethanol and other drugs, the present study assessed the role of KOR antagonism by nor-binaltorphimine (nor-BNI) on ethanol-induced conditioned taste aversion (CTA) in stressed (exposed to repeated restraint) and non-stressed male rats (Experiment 1), with half of the rats pretreated with nor-BNI before stressor exposure. In Experiment 2, CTA induced by the kappa agonist U62,066 was also compared in stressed and non-stressed adolescents and adults. A highly palatable solution (chocolate Boost) was used as the conditioned stimulus (CS), thereby avoiding the need for water deprivation to motivate consumption of the CS during conditioning. No effects of stress on ethanol-induced CTA were found, with all doses eliciting aversions in adolescents and adults in both stress conditions. However, among stressed subjects, adults given nor-BNI before the repeated stressor displayed blunted ethanol aversion relative to adults given saline at that time. This effect of nor-BNI was not seen in adolescents, findings that support a differential role for the KOR involvement in ethanol CTA in stressed adolescents and adults. Results from Experiment 2 revealed that all doses of U62,066 elicited aversions in non-stressed animals of both ages that were attenuated in stressed animals, findings that support a modulatory role for stress in aversive effects of KOR activation. Collectively, these results suggest that although KOR sensitivity appears to be reduced in stressed subjects, this receptor system does not appear to contribute to age differences in ethanol-induced CTA under the present test circumstances. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
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Awad, Walaa; Ferreira, Guillaume; Maroun, Mouna
2015-01-01
Medial prefrontal circuits have been reported to undergo a major reorganization over time and gradually take a more important role for remote emotional memories such as contextual fear memory or food aversion memory. The medial prefrontal cortex, and specifically its ventral subregion, the infralimbic cortex (IL), was also reported to be critical for recent memory extinction of contextual fear conditioning and conditioned odor aversion. However, its exact role in the extinction of remotely acquired information is still not clear. Using postretrieval blockade of protein synthesis or inactivation of the IL, we showed that the IL is similarly required for extinction consolidation of recent and remote fear memory. However, in odor aversion memory, the IL was only involved in extinction consolidation of recent, but not remote, memory. In contrast, only remote retrieval of aversion memory induced c-Fos activation in the IL and preretrieval inactivation of the IL with lidocaine impaired subsequent extinction of remote but not recent memory, indicating IL is necessary for extinction learning of remote aversion memory. In contrast to the effects in odor aversion, our data show that the involvement of the IL in the consolidation of fear extinction does not depend on the memory age. More importantly, our data indicate that the IL is implicated in the extinction of fear and nonfear-based associations and suggest dissociation in the engagement of the IL in the learning and consolidation of food aversion extinction over time. PMID:25872918
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Science in a Box. Body Works II: Test Your Taste.
ERIC Educational Resources Information Center
Learning, 1991
1991-01-01
Presents classroom learning activities to help elementary teachers and students learn about and experiment with the sense of taste. One involves tasting an apple while smelling an onion; another involves locating areas of the tongue that respond to salt, sweet, bitter, and sour. (SM)
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Dill, M Joelle; Shaw, Janice; Cramer, Jeff; Sindelar, Dana K
2013-11-01
Serotonin acts through receptors controlling several physiological functions, including energy homeostasis regulation and food intake. Recent experiments demonstrated that 5-HT1A receptor antagonists reduce food intake. We sought to examine the microstructure of feeding with 5-HT1A receptor antagonists using a food intake monitoring system. We also examined the relationship between food intake, inhibition of binding and pharmacokinetic (PK) profiles of the antagonists. Ex vivo binding revealed that, at doses used in this study to reduce food intake, inhibition of binding of a 5-HT1A agonist by ~40% was reached in diet-induced obese (DIO) mice with a trend for higher binding in DIO vs. lean animals. Additionally, PK analysis detected levels from 2 to 24h post-compound administration. Male DIO mice were administered 5-HT1A receptor antagonists LY439934 (10 or 30 mg/kg, p.o.), WAY100635 (3 or 10mg/kg, s.c.), SRA-333 (10 or 30 mg/kg, p.o.), or NAD-299 (3 or 10mg/kg, s.c.) for 3 days and meal patterns were measured. Analyses revealed that for each antagonist, 24-h food intake was reduced through a specific decrease in the total number of meals. Compared to controls, meal number was decreased 14-35% in the high dose. Average meal size was not changed by any of the compounds. The reduction in food intake reduced body weight 1-4% compared to Vehicle controls. Subsequently, a conditioned taste aversion (CTA) assay was used to determine whether the feeding decrease might be an indicator of aversion, nausea, or visceral illness caused by the antagonists. Using a two bottle preference test, it was found that none of the compounds produced a CTA. The decrease in food intake does not appear to be a response to nausea or malaise. These results indicate that 5-HT1A receptor antagonist suppresses feeding, specifically by decreasing the number of meals, and induce weight loss without an aversive side effect. © 2013 Elsevier Inc. All rights reserved.
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Developmental emergence of fear/threat learning: neurobiology, associations and timing.
Tallot, L; Doyère, V; Sullivan, R M
2016-01-01
Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive properties through pairing with an aversive stimulus, has been an important tool for exploring the neurobiology of learning. In the past decades, this neurobehavioral approach has been expanded to include the developing infant. Indeed, protracted postnatal brain development permits the exploration of how incorporating the amygdala, prefrontal cortex and hippocampus into this learning system impacts the acquisition and expression of aversive conditioning. Here, we review the developmental trajectory of these key brain areas involved in aversive conditioning and relate it to pups' transition to independence through weaning. Overall, the data suggests that adult-like features of threat learning emerge as the relevant brain areas become incorporated into this learning. Specifically, the developmental emergence of the amygdala permits cue learning and the emergence of the hippocampus permits context learning. We also describe unique features of learning in early life that block threat learning and enhance interaction with the mother or exploration of the environment. Finally, we describe the development of a sense of time within this learning and its involvement in creating associations. Together these data suggest that the development of threat learning is a useful tool for dissecting adult-like functioning of brain circuits, as well as providing unique insights into ecologically relevant developmental changes. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
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Stress attenuates the flexible updating of aversive value
Raio, Candace M.; Hartley, Catherine A.; Orederu, Temidayo A.; Li, Jian; Phelps, Elizabeth A.
2017-01-01
In a dynamic environment, sources of threat or safety can unexpectedly change, requiring the flexible updating of stimulus−outcome associations that promote adaptive behavior. However, aversive contexts in which we are required to update predictions of threat are often marked by stress. Acute stress is thought to reduce behavioral flexibility, yet its influence on the modulation of aversive value has not been well characterized. Given that stress exposure is a prominent risk factor for anxiety and trauma-related disorders marked by persistent, inflexible responses to threat, here we examined how acute stress affects the flexible updating of threat responses. Participants completed an aversive learning task, in which one stimulus was probabilistically associated with an electric shock, while the other stimulus signaled safety. A day later, participants underwent an acute stress or control manipulation before completing a reversal learning task during which the original stimulus−outcome contingencies switched. Skin conductance and neuroendocrine responses provided indices of sympathetic arousal and stress responses, respectively. Despite equivalent initial learning, stressed participants showed marked impairments in reversal learning relative to controls. Additionally, reversal learning deficits across participants were related to heightened levels of alpha-amylase, a marker of noradrenergic activity. Finally, fitting arousal data to a computational reinforcement learning model revealed that stress-induced reversal learning deficits emerged from stress-specific changes in the weight assigned to prediction error signals, disrupting the adaptive adjustment of learning rates. Our findings provide insight into how stress renders individuals less sensitive to changes in aversive reinforcement and have implications for understanding clinical conditions marked by stress-related psychopathology. PMID:28973957
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Dissociable Learning Processes Underlie Human Pain Conditioning
Zhang, Suyi; Mano, Hiroaki; Ganesh, Gowrishankar; Robbins, Trevor; Seymour, Ben
2016-01-01
Summary Pavlovian conditioning underlies many aspects of pain behavior, including fear and threat detection [1], escape and avoidance learning [2], and endogenous analgesia [3]. Although a central role for the amygdala is well established [4], both human and animal studies implicate other brain regions in learning, notably ventral striatum and cerebellum [5]. It remains unclear whether these regions make different contributions to a single aversive learning process or represent independent learning mechanisms that interact to generate the expression of pain-related behavior. We designed a human parallel aversive conditioning paradigm in which different Pavlovian visual cues probabilistically predicted thermal pain primarily to either the left or right arm and studied the acquisition of conditioned Pavlovian responses using combined physiological recordings and fMRI. Using computational modeling based on reinforcement learning theory, we found that conditioning involves two distinct types of learning process. First, a non-specific “preparatory” system learns aversive facial expressions and autonomic responses such as skin conductance. The associated learning signals—the learned associability and prediction error—were correlated with fMRI brain responses in amygdala-striatal regions, corresponding to the classic aversive (fear) learning circuit. Second, a specific lateralized system learns “consummatory” limb-withdrawal responses, detectable with electromyography of the arm to which pain is predicted. Its related learned associability was correlated with responses in ipsilateral cerebellar cortex, suggesting a novel computational role for the cerebellum in pain. In conclusion, our results show that the overall phenotype of conditioned pain behavior depends on two dissociable reinforcement learning circuits. PMID:26711494
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Lesions of the rat nucleus basalis magnocellularis disrupt appetitive-to-aversive transfer learning.
Butt, A E; Schultz, J A; Arnold, L L; Garman, E E; George, C L; Garraghty, P E
2003-01-01
Rats with selective lesions of the nucleus basalis magnocellularis (NBM) and sham-lesion control animals were tested in an operant appetitive-to-aversive transfer task. We hypothesized that NBM lesions would not affect performance in the appetitive phase, but that performance would be impaired during subsequent transfer to the aversive phase of the task. Additional groups of NBM lesion and control rats were tested in the avoidance condition only, where we hypothesized that NBM lesions would not disrupt performance. These hypotheses were based on the argument that the NBM is not necessary for simple association learning that does not tax attention. Both the appetitive phase of the transfer task and the avoidance only task depend only on simple associative learning and are argued not to tax attention. Consequently, performance in these tasks was predicted to be spared following NBM lesions. Complex, attention-demanding associative learning, however, is argued to depend on the NBM. Performance in the aversive phase of the transfer task is both attentionally demanding and associatively more complex than in either the appetitive or aversive tasks alone; thus, avoidance performance in the NBM lesion group was predicted to be impaired following transfer from prior appetitive conditioning. Results supported our hypotheses, with the NBM lesion group acquiring the appetitive response normally, but showing impaired performance following transfer to the aversive conditioning phase of the transfer task. Impairments were not attributable to disrupted avoidance learning per se, as avoidance behavior was normal in the NBM lesion group tested in the avoidance condition only.
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Tauber, John M.; Li, Yuanyuan; Yurgel, Maria E.; Masek, Pavel
2017-01-01
Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass. The highly palatable taste of free fatty acids (FAs), one of the building blocks of fat, promotes food consumption, activates reward circuitry, and is thought to contribute to hedonic feeding underlying many metabolism-related disorders. Despite a role in the etiology of metabolic diseases, little is known about how dietary fats are detected by the gustatory system to promote feeding. Previously, we showed that a broad population of sugar-sensing taste neurons expressing Gustatory Receptor 64f (Gr64f) is required for reflexive feeding responses to both FAs and sugars. Here, we report a genetic silencing screen to identify specific populations of taste neurons that mediate fatty acid (FA) taste. We find neurons identified by expression of Ionotropic Receptor 56d (IR56d) are necessary and sufficient for reflexive feeding response to FAs. Functional imaging reveals that IR56d-expressing neurons are responsive to short- and medium-chain FAs. Silencing IR56d neurons selectively abolishes FA taste, and their activation is sufficient to drive feeding responses. Analysis of co-expression with Gr64f identifies two subpopulations of IR56d-expressing neurons. While physiological imaging reveals that both populations are responsive to FAs, IR56d/Gr64f neurons are activated by medium-chain FAs and are sufficient for reflexive feeding response to FAs. Moreover, flies can discriminate between sugar and FAs in an aversive taste memory assay, indicating that FA taste is a unique modality in Drosophila. Taken together, these findings localize FA taste within the Drosophila gustatory center and provide an opportunity to investigate discrimination between different categories of appetitive tastants. PMID:29121639
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Role for the Rostromedial Tegmental Nucleus in Signaling the Aversive Properties of Alcohol.
Glover, Elizabeth J; McDougle, Molly J; Siegel, Griffin S; Jhou, Thomas C; Chandler, L Judson
2016-08-01
While the rewarding effects of alcohol contribute significantly to its addictive potential, it is becoming increasingly appreciated that alcohol's aversive properties also play an important role in the propensity to drink. Despite this, the neurobiological mechanism for alcohol's aversive actions is not well understood. The rostromedial tegmental nucleus (RMTg) was recently characterized for its involvement in aversive signaling and has been shown to encode the aversive properties of cocaine, yet its involvement in alcohol's aversive actions have not been elucidated. Adult male and female Long-Evans rats underwent conditioned taste aversion (CTA) procedures where exposure to a novel saccharin solution was paired with intraperitoneal administration of saline, lithium chloride (LiCl), or ethanol (EtOH). Control rats underwent the same paradigm except that drug and saccharin exposure were explicitly unpaired. Saccharin consumption was measured on test day in the absence of drug administration, and rats were sacrificed 90 to 105 minutes following access to saccharin. Brains were subsequently harvested and processed for cFos immunohistochemistry. The number of cFos-labeled neurons was counted in the RMTg and the lateral habenula (LHb)-a region that sends prominent glutamatergic input to the RMTg. In rats that received paired drug and saccharin exposure, EtOH and LiCl induced significant CTA compared to saline to a similar degree in males and females. Both EtOH- and LiCl-induced CTA significantly enhanced cFos expression in the RMTg and LHb but not the hippocampus. Similar to behavioral measures, no significant effect of sex on CTA-induced cFos expression was observed. cFos expression in both the RMTg and LHb was significantly correlated with CTA magnitude with greater cFos being associated with more pronounced CTA. In addition, cFos expression in the RMTg was positively correlated with LHb cFos. These data suggest that the RMTg and LHb are involved in the expression of CTA and are consistent with previous work implicating the RMTg in aversive signaling. Furthermore, increased cFos expression in the RMTg following EtOH-induced CTA suggests that this region plays a role in signaling alcohol's aversive properties. Copyright © 2016 by the Research Society on Alcoholism.
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Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli
Boughter, John D; Raghow, Sandeep; Nelson, Theodore M; Munger, Steven D
2005-01-01
Background Common inbred mouse strains are genotypically diverse, but it is still poorly understood how this diversity relates to specific differences in behavior. To identify quantitative trait genes that influence taste behavior differences, it is critical to utilize assays that exclusively measure the contribution of orosensory cues. With a few exceptions, previous characterizations of behavioral taste sensitivity in inbred mouse strains have generally measured consumption, which can be confounded by post-ingestive effects. Here, we used a taste-salient brief-access procedure to measure taste sensitivity to eight stimuli characterized as bitter or aversive in C57BL/6J (B6) and DBA/2J (D2) mice. Results B6 mice were more sensitive than D2 mice to a subset of bitter stimuli, including quinine hydrochloride (QHCl), 6-n-propylthiouracil (PROP), and MgCl2. D2 mice were more sensitive than B6 mice to the bitter stimulus raffinose undecaacetate (RUA). These strains did not differ in sensitivity to cycloheximide (CYX), denatonium benzoate (DB), KCl or HCl. Conclusion B6-D2 taste sensitivity differences indicate that differences in consumption of QHCl, PROP, MgCl2 and RUA are based on immediate orosensory cues, not post-ingestive effects. The absence of a strain difference for CYX suggests that polymorphisms in a T2R-type taste receptor shown to be differentially sensitive to CYX in vitro are unlikely to differentially contribute to the CYX behavioral response in vivo. The results of these studies point to the utility of these common mouse strains and their associated resources for investigation into the genetic mechanisms of taste. PMID:15967025
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Noble, Emily E.; Billington, Charles J.; Kotz, Catherine M.
2014-01-01
Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin. PMID:24990860
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Taste responses in mice lacking taste receptor subunit T1R1
Kusuhara, Yoko; Yoshida, Ryusuke; Ohkuri, Tadahiro; Yasumatsu, Keiko; Voigt, Anja; Hübner, Sandra; Maeda, Katsumasa; Boehm, Ulrich; Meyerhof, Wolfgang; Ninomiya, Yuzo
2013-01-01
The T1R1 receptor subunit acts as an umami taste receptor in combination with its partner, T1R3. In addition, metabotropic glutamate receptors (brain and taste variants of mGluR1 and mGluR4) are thought to function as umami taste receptors. To elucidate the function of T1R1 and the contribution of mGluRs to umami taste detection in vivo, we used newly developed knock-out (T1R1−/−) mice, which lack the entire coding region of the Tas1r1 gene and express mCherry in T1R1-expressing cells. Gustatory nerve recordings demonstrated that T1R1−/− mice exhibited a serious deficit in inosine monophosphate-elicited synergy but substantial residual responses to glutamate alone in both chorda tympani and glossopharyngeal nerves. Interestingly, chorda tympani nerve responses to sweeteners were smaller in T1R1−/− mice. Taste cell recordings demonstrated that many mCherry-expressing taste cells in T1R1+/− mice responded to sweet and umami compounds, whereas those in T1R1−/− mice responded to sweet stimuli. The proportion of sweet-responsive cells was smaller in T1R1−/− than in T1R1+/− mice. Single-cell RT-PCR demonstrated that some single mCherry-expressing cells expressed all three T1R subunits. Chorda tympani and glossopharyngeal nerve responses to glutamate were significantly inhibited by addition of mGluR antagonists in both T1R1−/− and T1R1+/− mice. Conditioned taste aversion tests demonstrated that both T1R1−/− and T1R1+/− mice were equally capable of discriminating glutamate from other basic taste stimuli. Avoidance conditioned to glutamate was significantly reduced by addition of mGluR antagonists. These results suggest that T1R1-expressing cells mainly contribute to umami taste synergism and partly to sweet sensitivity and that mGluRs are involved in the detection of umami compounds. PMID:23339178
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Differential Endocannabinoid Regulation of Extinction in Appetitive and Aversive Barnes Maze Tasks
ERIC Educational Resources Information Center
Harloe, John P.; Thorpe, Andrew J.; Lichtman, Aron H.
2008-01-01
CB[subscript 1] receptor-compromised animals show profound deficits in extinguishing learned behavior from aversive conditioning tasks, but display normal extinction learning in appetitive operant tasks. However, it is difficult to discern whether the differential involvement of the endogenous cannabinoid system on extinction results from the…
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A pain in the bud? Implications of cross-modal sensitivity for pain experience.
Perkins, Monica; de Bruyne, Marien; Giummarra, Melita J
2016-11-01
There is growing evidence that enhanced sensitivity to painful clinical procedures and chronic pain are related to greater sensitivity to other sensory inputs, such as bitter taste. We examined cross-modal sensitivities in two studies. Study 1 assessed associations between bitter taste sensitivity, pain tolerance, and fear of pain in 48 healthy young adults. Participants were classified as non-tasters, tasters and super-tasters using a bitter taste test (6-n-propythiouracil; PROP). The latter group had significantly higher fear of pain (Fear of Pain Questionnaire) than tasters (p=.036, effect size r = .48). There was only a trend for an association between bitter taste intensity ratings and intensity of pain at the point of pain tolerance in a cold pressor test (p=.04). In Study 2, 40 healthy young adults completed the Adolescent/Adult Sensory Profile before rating intensity and unpleasantness of innocuous (33 °C), moderate (41 °C), and high intensity (44 °C) thermal pain stimulations. The sensory-sensitivity subscale was positively correlated with both intensity and unpleasantness ratings. Canonical correlation showed that only sensitivity to audition and touch (not taste/smell) were associated with intensity of moderate and high (not innocuous) thermal stimuli. Together these findings suggest that there are cross-modal associations predominantly between sensitivity to exteroceptive inputs (i.e., taste, touch, sound) and the affective dimensions of pain, including noxious heat and intolerable cold pain, in healthy adults. These cross-modal sensitivities may arise due to greater psychological aversion to salient sensations, or from shared neural circuitry for processing disparate sensory modalities.
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Prescott, M J; Buchanan-Smith, H M; Smith, A C
2005-04-01
For social species, being a member of a cohesive group and performing activities as a coordinated unit appear to provide a mechanism for the efficient transmission of information about food. Social learning about food palatability was investigated in two captive primates, Saguinus fuscicollis and S. labiatus, which form stable and cohesive mixed-species groups in the wild. We explored whether an induced food aversion toward a preferred food is modified during and after social interaction with non-averse conspecifics or congeners. Sets of intra- and interspecific pairs were presented with two foods, one of which was considered distasteful by one of the pairs (the other was palatable), and their behavior was compared pre-interaction, during interaction, and post-interaction. For the aversely-conditioned individuals of both species, the change in social context corresponded to a change in their preference for the food that they considered unpalatable, regardless of whether they had interacted with a conspecific or congeneric pair, and the change in food preference was maintained post-interaction. In a control condition, in which averse individuals did not have the opportunity to interact with non-averse animals, S. fuscicollis sampled the preferred food, but not as quickly as when given the opportunity to interact. We conclude that the social learning demonstrated here may allow individual tamarins to track environmental change, such as fruit ripening, more efficiently than asocial learning alone, because social learners can more quickly and safely focus on appropriate behavior by sharing up-to-date foraging information. Furthermore, since the behavior of congeners, as well as conspecifics, acts to influence food choice in a more adaptive direction, social learning about food palatability may be an advantage of mixed-species group formation to tamarins of both species. Copyright 2005 Wiley-Liss, Inc
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Dissociable Learning Processes Underlie Human Pain Conditioning.
Zhang, Suyi; Mano, Hiroaki; Ganesh, Gowrishankar; Robbins, Trevor; Seymour, Ben
2016-01-11
Pavlovian conditioning underlies many aspects of pain behavior, including fear and threat detection [1], escape and avoidance learning [2], and endogenous analgesia [3]. Although a central role for the amygdala is well established [4], both human and animal studies implicate other brain regions in learning, notably ventral striatum and cerebellum [5]. It remains unclear whether these regions make different contributions to a single aversive learning process or represent independent learning mechanisms that interact to generate the expression of pain-related behavior. We designed a human parallel aversive conditioning paradigm in which different Pavlovian visual cues probabilistically predicted thermal pain primarily to either the left or right arm and studied the acquisition of conditioned Pavlovian responses using combined physiological recordings and fMRI. Using computational modeling based on reinforcement learning theory, we found that conditioning involves two distinct types of learning process. First, a non-specific "preparatory" system learns aversive facial expressions and autonomic responses such as skin conductance. The associated learning signals-the learned associability and prediction error-were correlated with fMRI brain responses in amygdala-striatal regions, corresponding to the classic aversive (fear) learning circuit. Second, a specific lateralized system learns "consummatory" limb-withdrawal responses, detectable with electromyography of the arm to which pain is predicted. Its related learned associability was correlated with responses in ipsilateral cerebellar cortex, suggesting a novel computational role for the cerebellum in pain. In conclusion, our results show that the overall phenotype of conditioned pain behavior depends on two dissociable reinforcement learning circuits. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Torregrossa, Ann-Marie; Nikonova, Larissa; Bales, Michelle B.; Villalobos Leal, Maria; Smith, James C.; Contreras, Robert J.; Eckel, Lisa A.
2014-01-01
There are hundreds of proteins in saliva. Although it has long been hypothesized that these proteins modulate taste by interacting with taste receptors or taste stimuli, the functional impact of these proteins on feeding remains relatively unexplored. We have developed a new technique for saliva collection that does not interfere with daily behavioral testing and allows us to explore the relationship between feeding behavior and salivary protein expression. First, we monitored the alterations in salivary protein expression while simultaneously monitoring the animals' feeding behavior and meal patterns on a custom control diet or on the same diet mixed with 3% tannic acid. We demonstrated that six protein bands increased in density with dietary tannic acid exposure. Several of these bands were significantly correlated with behaviors thought to represent both orosensory and postingestive signaling. In a follow-up experiment, unconditioned licking to 0.01–3% tannic acid solutions was measured during a brief-access taste test before and after exposure to the tannic acid diet. In this experiment, rats with salivary proteins upregulated found the tannin solution less aversive (i.e., licked more) than those in the control condition. These data suggest a role for salivary proteins in mediating changes in both orosensory and postingestive feedback. PMID:25162297
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Ancel, Déborah; Bernard, Arnaud; Subramaniam, Selvakumar; Hirasawa, Akira; Tsujimoto, Gozoh; Hashimoto, Toshihiro; Passilly-Degrace, Patricia; Khan, Naim-Akhtar; Besnard, Philippe
2015-01-01
Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the “taste of fat”, the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological [i.e., immunohistochemical staining of circumvallate papillae (CVP)], behavioral (i.e., two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies [i.e., calcium imaging in freshly isolated taste bud cells (TBCs)], we show that absence of GPR120 in the oral cavity was not associated with changes in i) gross anatomy of CVP, ii) LCFA-mediated increases in intracellular calcium levels ([Ca2+]i), iii) preference for oily and LCFA solutions and iv) conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca2+]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking. Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice PMID:25489006
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Hirose, Nozomi; Kawabata, Yuko; Kawabata, Fuminori; Nishimura, Shotaro; Tabata, Shoji
2015-05-01
Clarification of the mechanism of the sense of taste in chickens will provide information useful for creating and improving new feedstuffs for chickens, because the character of the taste receptors in oral tissues affects feeding behavior in animals. In this study, we focused on the sensitivity to bitterness in chickens. We cloned one of the bitter taste receptors, T2R1, from the chicken palate, constructed several biosensor-cells expressing chicken T2R1 (cT2R1), and determined a highly sensitive biosensor of cT2R1 among them. By using Ca(2+) imaging methods, we identified two agonists of cT2R1, dextromethorphan (Dex) and diphenidol (Dip). Dex was a new agonist of cT2R1 that was more potent than Dip. In a behavioral drinking study, the intake volumes of solutions of these compounds were significantly lower than that of water in chickens. These aversive concentrations were identical to the concentrations that could activate cT2R1 in a cell-based assay. These results suggest that the cT2R1 activities induced by these agonists are linked to behavioral sensitivity to bitterness in chickens. Copyright © 2015 Elsevier Inc. All rights reserved.
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Cycloheximide: No Ordinary Bitter Stimulus
Hettinger, Thomas P.; Formaker, Bradley K.; Frank, Marion E.
2007-01-01
Cycloheximide (CyX), a toxic antibiotic with a unique chemical structure generated by the actinomycete, Streptomyces griseus, has emerged as a primary focus of studies on mammalian bitter taste. Rats and mice avoid it at concentrations well below the thresholds for most bitter stimuli and T2R G-protein-coupled receptors specific for CyX with appropriate sensitivity are identified for those species. Like mouse and rat, golden hamsters, Mesocricetus auratus, also detected and rejected micromolar levels of CyX, although 1 mM CyX failed to activate the hamster chorda tympani nerve. Hamsters showed an initial tolerance for 500 μM CyX, but after that, avoidance of CyX dramatically increased, plasticity not reported for rat or mouse. As the hamster lineage branches well before division of the mouse-rat lineage in evolutionary time, differences between hamster and mouse-rat reactions to CyX are not surprising. Furthermore, unlike hamster LiCl-induced learned aversions, the induced CyX aversion neither specifically nor robustly generalized to other non-ionic bitter stimuli; and unlike adverse reactions to other chemosensory stimuli, aversions to CyX were not mollified by adding a sweetener. Thus, CyX is unlike other bitter stimuli. The gene for the high-affinity CyX receptor is a member of a cluster of 5 orthologous T2R genes that are likely rodent specific; this “CyX clade” is found in the mouse, rat and probably hamster, but not in the human or rabbit genome. The rodent CyX-T2R interaction may be one of multiple lineage-specific stimulus-receptor interactions reflecting a response to a particular environmental toxin. The combination of T2R multiplicity, species divergence and gene duplication results in diverse ligands for multiple species-specific T2R receptors, which confounds definition of ‘bitter’ stimuli across species. PMID:17400304
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The Bad Taste of Medicines: Overview of Basic Research on Bitter Taste
Mennella, Julie A.; Spector, Alan C.; Reed, Danielle R.; Coldwell, Susan E.
2013-01-01
Background Many active pharmaceutical ingredients taste bitter and thus are aversive to children, as well as many adults. Encapsulation of the medicine in pill or tablet form, an effective method for adults to avoid the unpleasant taste, is problematic for children. Many children cannot or will not swallow solid dosage forms. Objective This review highlights basic principles of gustatory function, with a special focus on the science of bitter taste, derived from studies of animal models and human psychophysics. We focus on the set of genes that encode the proteins that function as bitter receptors, as well as the cascade of events that lead to multidimensional aspects of taste function, highlighting the role that animal models played in these discoveries. We also summarize psychophysical approaches to studying bitter taste in adult and pediatric populations, highlighting evidence of the similarities and differences in bitter taste perception and acceptance between adults and children and drawing on useful strategies from animal models. Results Medicine often tastes bitter, and because children are more bitter sensitive than are adults, this creates problems with compliance. Bitter arises from stimulating receptors in taste receptor cells, with signals processed in the taste bud and relayed to the brain. However, there are many gaps in our understanding of how best to measure bitterness and how to ameliorate it, including whether it is more efficiently addressed at the level of receptor and sensory signaling, at the level of central processing, or by masking techniques. All methods of measuring responsiveness to bitter ligands—in animal models, through human psychophysics, or with “electronic tongues”—have limitations. Conclusions Better-tasting medications may enhance pediatric adherence to drug therapy. Sugars, acids, salt, and other substances reduce perceived bitterness of several pharmaceuticals, and although pleasant flavorings may help children consume some medicines, they often are not effective in suppressing bitter tastes. Further development of psychophysical tools for children will help us better understand their sensory worlds. Multiple testing strategies will help us refine methods to assess acceptance and compliance/adherence by various pediatric populations. Research involving animal models, in which the gustatory system can be more invasively manipulated, can elucidate mechanisms, ultimately providing potential targets. These approaches, combined with new technologies and guided by findings from clinical studies, will potentially lead to effective ways to enhance drug acceptance and compliance in pediatric populations. PMID:23886820
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An fMRI study on the influence of sommeliers' expertise on the integration of flavor
Pazart, Lionel; Comte, Alexandre; Magnin, Eloi; Millot, Jean-Louis; Moulin, Thierry
2014-01-01
Flavors guide consumers' choice of foodstuffs, preferring those that they like and meet their needs, and dismissing those for which they have a conditioned aversion. Flavor affects the learning and consumption of foods and drinks; what is already well-known is favored and what is new is apprehended. The flavor of foodstuffs is also crucial in explaining some eating behaviors such as overconsumption. The “blind” taste test of wine is a good model for assessing the ability of people to convert mouth feelings into flavor. To determine the relative importance of memory and sensory capabilities, we present the results of an fMRI neuro-imaging study involving 10 experts and 10 matched control subjects using wine as a stimulus in a blind taste test, focusing primarily on the assessment of flavor integration. The results revealed activations in the brain areas involved in sensory integration, both in experts and control subjects (insula, frontal operculum, orbitofrontal cortex, amygdala). However, experts were mainly characterized by a more immediate and targeted sensory reaction to wine stimulation with an economic mechanism reducing effort than control subjects. Wine experts showed brainstem and left-hemispheric activations in the hippocampal and parahippocampal formations and the temporal pole, whereas control subjects showed activations in different associative cortices, predominantly in the right hemisphere. These results also confirm that wine experts work simultaneously on sensory quality assessment and on label recognition of wine. PMID:25360093
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Flavor Perception in Human Infants: Development and Functional Significance
Beauchamp, Gary K.; Mennella, Julie A.
2011-01-01
Background Foods people consume impact on their health in many ways. In particular, excess intake of salty, sweet and fatty foods and inadequate intake of fruits and vegetables have been related to many diseases including diabetes, hypertension, cardiovascular disease and some cancers. The flavor of a food determines its acceptability and modulates intake. It is thus critical to understand the factors that influence flavor preferences in humans. Aim: To outline several of the important factors that shape flavor preferences in humans. Methods We review a series of studies, mainly from our laboratories, on the important role of early experiences with flavors on subsequent flavor preference and food intake. Results and Conclusions: Some taste preferences and aversions (e.g. liking for sweet, salty and umami; disliking for bitter) are innately organized, although early experiences can modify their expression. In utero events may impact on later taste and flavor preferences and modulate intake of nutrients. Both before and after birth, humans are exposed to a bewildering variety of flavors that influence subsequent liking and choice. Fetuses are exposed to flavors in amniotic fluid modulating preferences later in life and flavor learning continues after birth. Experience with flavors that are bitter, sour or have umami characteristics, as well as volatile flavors such as carrot and garlic, occurs through flavorings in breast milk, infant formula and early foods. These early experiences mold long-term food and flavor preferences which can impact upon later health. PMID:21389721
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Gustatory Learning and Processing in the Drosophila Mushroom Bodies
Kirkhart, Colleen
2015-01-01
The Drosophila mushroom bodies are critical association areas whose role in olfactory associative learning has been well characterized. Recent behavioral studies using a taste association paradigm revealed that gustatory conditioning also requires the mushroom bodies (Masek and Scott, 2010; Keene and Masek, 2012). Here, we examine the representations of tastes and the neural sites for taste associations in the mushroom bodies. Using molecular genetic approaches to target different neuronal populations, we find that the gamma lobes of the mushroom bodies and a subset of dopaminergic input neurons are required for taste associative learning. Monitoring responses to taste compounds in the mushroom body calyx with calcium imaging reveals sparse, taste-specific and organ-specific activation in the Kenyon cell dendrites of the main calyx and the dorsal accessory calyx. Our work provides insight into gustatory representations in the mushroom bodies, revealing the essential role of gustatory inputs not only as rewards and punishments but also as adaptive cues. PMID:25878268
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Nekitsing, Chandani; Hetherington, Marion M; Blundell-Birtill, Pam
2018-03-01
The present review was undertaken in order to summarize and evaluate recent research investigating taste exposure, sensory learning, and nutrition education interventions for promoting vegetable intake in preschool children. Overall, taste exposure interventions yielded the best outcomes for increasing vegetable intake in early childhood. Evidence from sensory learning strategies such as visual exposure and experiential learning also show some success. While nutrition education remains the most common approach used in preschool settings, additional elements are needed to strengthen the educational program for increasing vegetable intake. There is a substantial gap in the evidence base to promote vegetable intake in food fussy children. The present review reveals the relative importance of different intervention strategies for promoting vegetable intake. To strengthen intervention effects for improving vegetable intake in preschool children, future research could consider integrating taste exposure and sensory learning strategies with nutrition education within the preschool curriculum.
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Jensen, Kim; Schal, Coby; Silverman, Jules
2015-10-01
Insects have evolved fine-tuned gustatory and post-ingestive physiological mechanisms that enable them to self-select an optimal composition of macronutrients. Their ability to forage optimally among multiple food sources and maximize fitness parameters depends on their ability not only to taste and perceive the nutritional value of potential foods but also to avoid deleterious components; the strength of such avoidance should reflect the severity of the perceived hazard. In German cockroaches (Blattella germanica), glucose aversion has evolved in some populations in response to anthropogenic selection with glucose-containing insecticidal baits. In four feeding treatments, we gave newly eclosed glucose-averse female cockroaches free choice to feed from two artificial, nutritionally complementary foods varying in protein and carbohydrate composition, with glucose or fructose as the sole carbohydrate source in either food. After 6days of feeding, we measured diet consumption and the length of basal oocytes as an estimate of sexual maturation. The females did not compromise on their aversion to glucose in order to balance their protein and carbohydrate intake, and experienced lower sexual maturation rates as a consequence. Nutrient specific hunger via feedback mechanisms, and adjustments to gustatory sensitivity thus do not override the deterrence of glucose, likely due to strong selection against ingesting even small amounts of toxin associated with glucose in baits. In the absence of baits, glucose aversion would be expected to incur a fitness cost compared to wild-type individuals due to lower overall food availability but also to larger difficulty in attaining a nutritionally balanced diet. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Differential Involvement of the Central Amygdala in Appetitive versus Aversive Learning
ERIC Educational Resources Information Center
Lipp, Hans-Peter; Kaczmarek, Leszek; Werka, Tomasz; Knapska, Ewelina; Walasek, Grazyna; Nikolaev, Evgeni; Neuhausser-Wespy, Frieder
2006-01-01
Understanding the function of the distinct amygdaloid nuclei in learning comprises a major challenge. In the two studies described herein, we used c-Fos immunolabeling to compare the engagement of various nuclei of the amygdala in appetitive and aversive instrumental training procedures. In the first experiment, rats that had already acquired a…
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Ilango, A; Wetzel, W; Scheich, H; Ohl, F W
2010-03-31
Learned changes in behavior can be elicited by either appetitive or aversive reinforcers. It is, however, not clear whether the two types of motivation, (approaching appetitive stimuli and avoiding aversive stimuli) drive learning in the same or different ways, nor is their interaction understood in situations where the two types are combined in a single experiment. To investigate this question we have developed a novel learning paradigm for Mongolian gerbils, which not only allows rewards and punishments to be presented in isolation or in combination with each other, but also can use these opposite reinforcers to drive the same learned behavior. Specifically, we studied learning of tone-conditioned hurdle crossing in a shuttle box driven by either an appetitive reinforcer (brain stimulation reward) or an aversive reinforcer (electrical footshock), or by a combination of both. Combination of the two reinforcers potentiated speed of acquisition, led to maximum possible performance, and delayed extinction as compared to either reinforcer alone. Additional experiments, using partial reinforcement protocols and experiments in which one of the reinforcers was omitted after the animals had been previously trained with the combination of both reinforcers, indicated that appetitive and aversive reinforcers operated together but acted in different ways: in this particular experimental context, punishment appeared to be more effective for initial acquisition and reward more effective to maintain a high level of conditioned responses (CRs). The results imply that learning mechanisms in problem solving were maximally effective when the initial punishment of mistakes was combined with the subsequent rewarding of correct performance. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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Fetal ethanol exposure increases ethanol intake by making it smell and taste better
Youngentob, Steven L.; Glendinning, John I.
2009-01-01
Human epidemiologic studies reveal that fetal ethanol exposure is highly predictive of adolescent ethanol avidity and abuse. Little is known about how fetal exposure produces these effects. It is hypothesized that fetal ethanol exposure results in stimulus-induced chemosensory plasticity. Here, we asked whether gestational ethanol exposure increases postnatal ethanol avidity in rats by altering its taste and odor. Experimental rats were exposed to ethanol in utero via the dam's diet, whereas control rats were either pair-fed an iso-caloric diet or given food ad libitum. We found that fetal ethanol exposure increased the taste-mediated acceptability of both ethanol and quinine hydrochloride (bitter), but not sucrose (sweet). Importantly, a significant proportion of the increased ethanol acceptability could be attributed directly to the attenuated aversion to ethanol's quinine-like taste quality. Fetal ethanol exposure also enhanced ethanol intake and the behavioral response to ethanol odor. Notably, the elevated intake of ethanol was also causally linked to the enhanced odor response. Our results demonstrate that fetal exposure specifically increases ethanol avidity by, in part, making it taste and smell better. More generally, they establish an epigenetic chemosensory mechanism by which maternal patterns of drug use can be transferred to offspring. Given that many licit (e.g., tobacco products) and illicit (e.g., marijuana) drugs have noteworthy chemosensory components, our findings have broad implications for the relationship between maternal patterns of drug use, child development, and postnatal vulnerability. PMID:19273846
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Fetal ethanol exposure increases ethanol intake by making it smell and taste better.
Youngentob, Steven L; Glendinning, John I
2009-03-31
Human epidemiologic studies reveal that fetal ethanol exposure is highly predictive of adolescent ethanol avidity and abuse. Little is known about how fetal exposure produces these effects. It is hypothesized that fetal ethanol exposure results in stimulus-induced chemosensory plasticity. Here, we asked whether gestational ethanol exposure increases postnatal ethanol avidity in rats by altering its taste and odor. Experimental rats were exposed to ethanol in utero via the dam's diet, whereas control rats were either pair-fed an iso-caloric diet or given food ad libitum. We found that fetal ethanol exposure increased the taste-mediated acceptability of both ethanol and quinine hydrochloride (bitter), but not sucrose (sweet). Importantly, a significant proportion of the increased ethanol acceptability could be attributed directly to the attenuated aversion to ethanol's quinine-like taste quality. Fetal ethanol exposure also enhanced ethanol intake and the behavioral response to ethanol odor. Notably, the elevated intake of ethanol was also causally linked to the enhanced odor response. Our results demonstrate that fetal exposure specifically increases ethanol avidity by, in part, making it taste and smell better. More generally, they establish an epigenetic chemosensory mechanism by which maternal patterns of drug use can be transferred to offspring. Given that many licit (e.g., tobacco products) and illicit (e.g., marijuana) drugs have noteworthy chemosensory components, our findings have broad implications for the relationship between maternal patterns of drug use, child development, and postnatal vulnerability.
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Low body temperature, time dilation, and long-trace conditioned flavor aversion in rats.
Misanin, James R; Anderson, Matthew J; Christianson, John P; Collins, Michele M; Goodhart, Mark G; Rushanan, Scott G; Hinderliter, Charles F
2002-07-01
Conditioned flavor aversion was examined in Wistar-derived albino rats that were immersed in cold water for 0, 2.5, 5, or 10 min immediately following 10-min exposure to a.1% saccharin solution and given an intraperitoneal (i.p.) injection of 0.15 M lithium chloride (LiCl) either 90, 135, 180, or 225 min later. Cold water immersion for 2.5, 5, and 10 min led to body temperature decreases of approximately 4.5, 7, and 10 degrees C, respectively. Rats whose body temperatures were not reduced (0 min immersion) showed no saccharin aversion when the LiCl was delayed 90 min. Rats whose body temperatures were reduced 4.5, 7, and 10 degrees C displayed conditioned aversions at LiCl delays up to 135, 180, and 225 min, respectively. These results were interpreted in terms of a cold-induced slowing of a biochemical clock that may uniquely govern specific timing processes involved in associative learning over long delays, such as long-trace conditioned flavor aversion, learned safety, and certain types of learning that involve an extensive time lapse (e.g., extinction of fear). Copyright 2002 Elsevier Science (USA).
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Olfactory modulation by dopamine in the context of aversive learning
Riffell, Jeffrey A.; Martin, Joshua P.; Gage, Stephanie L.; Nighorn, Alan J.
2012-01-01
The need to detect and process sensory cues varies in different behavioral contexts. Plasticity in sensory coding can be achieved by the context-specific release of neuromodulators in restricted brain areas. The context of aversion triggers the release of dopamine in the insect brain, yet the effects of dopamine on sensory coding are unknown. In this study, we characterize the morphology of dopaminergic neurons that innervate each of the antennal lobes (ALs; the first synaptic neuropils of the olfactory system) of the moth Manduca sexta and demonstrate with electrophysiology that dopamine enhances odor-evoked responses of the majority of AL neurons while reducing the responses of a small minority. Because dopamine release in higher brain areas mediates aversive learning we developed a naturalistic, ecologically inspired aversive learning paradigm in which an innately appetitive host plant floral odor is paired with a mimic of the aversive nectar of herbivorized host plants. This pairing resulted in a decrease in feeding behavior that was blocked when dopamine receptor antagonists were injected directly into the ALs. These results suggest that a transient dopaminergic enhancement of sensory output from the AL contributes to the formation of aversive memories. We propose a model of olfactory modulation in which specific contexts trigger the release of different neuromodulators in the AL to increase olfactory output to downstream areas of processing. PMID:22552185
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Negative learning bias is associated with risk aversion in a genetic animal model of depression.
Shabel, Steven J; Murphy, Ryan T; Malinow, Roberto
2014-01-01
The lateral habenula (LHb) is activated by aversive stimuli and the omission of reward, inhibited by rewarding stimuli and is hyperactive in helpless rats-an animal model of depression. Here we test the hypothesis that congenital learned helpless (cLH) rats are more sensitive to decreases in reward size and/or less sensitive to increases in reward than wild-type (WT) control rats. Consistent with the hypothesis, we found that cLH rats were slower to switch preference between two responses after a small upshift in reward size on one of the responses but faster to switch their preference after a small downshift in reward size. cLH rats were also more risk-averse than WT rats-they chose a response delivering a constant amount of reward ("safe" response) more often than a response delivering a variable amount of reward ("risky" response) compared to WT rats. Interestingly, the level of bias toward negative events was associated with the rat's level of risk aversion when compared across individual rats. cLH rats also showed impaired appetitive Pavlovian conditioning but more accurate responding in a two-choice sensory discrimination task. These results are consistent with a negative learning bias and risk aversion in cLH rats, suggesting abnormal processing of rewarding and aversive events in the LHb of cLH rats.
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Blednov, Y A; Benavidez, J M; Black, M; Chandra, D; Homanics, G E; Rudolph, U; Harris, R A
2013-04-01
GABA type A receptors (GABA(A)-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABA(A)-R subunits (α1, α2, α3, α4, α5 and δ). Only mice lacking the α2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the α2-subunit (Blednov et al., 2011). All together, they indicate that aversive property of ethanol is dependent on ethanol action on α2-containing GABA(A)-R. Deletion of the α2-subunit led to faster recovery whereas absence of the α3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the α2 and α3 null mutants were found for flurazepam motor incoordination. However, no differences in recovery were found in motor-incoordinating effects of an α1-selective modulator (zolpidem) or an α4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABA(A)-R subunits: α2 and α3. For motor activity, α3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both α2 (-/-) and α3 (-/Y) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing α2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the α2 subunit with human alcoholism. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Behavioral consequences of dopamine deficiency in the Drosophila central nervous system
Riemensperger, Thomas; Isabel, Guillaume; Coulom, Hélène; Neuser, Kirsa; Seugnet, Laurent; Kume, Kazuhiko; Iché-Torres, Magali; Cassar, Marlène; Strauss, Roland; Preat, Thomas; Hirsh, Jay; Birman, Serge
2011-01-01
The neuromodulatory function of dopamine (DA) is an inherent feature of nervous systems of all animals. To learn more about the function of neural DA in Drosophila, we generated mutant flies that lack tyrosine hydroxylase, and thus DA biosynthesis, selectively in the nervous system. We found that DA is absent or below detection limits in the adult brain of these flies. Despite this, they have a lifespan similar to WT flies. These mutants show reduced activity, extended sleep time, locomotor deficits that increase with age, and they are hypophagic. Whereas odor and electrical shock avoidance are not affected, aversive olfactory learning is abolished. Instead, DA-deficient flies have an apparently “masochistic” tendency to prefer the shock-associated odor 2 h after conditioning. Similarly, sugar preference is absent, whereas sugar stimulation of foreleg taste neurons induces normal proboscis extension. Feeding the DA precursor l-DOPA to adults substantially rescues the learning deficit as well as other impaired behaviors that were tested. DA-deficient flies are also defective in positive phototaxis, without alteration in visual perception and optomotor response. Surprisingly, visual tracking is largely maintained, and these mutants still possess an efficient spatial orientation memory. Our findings show that flies can perform complex brain functions in the absence of neural DA, whereas specific behaviors involving, in particular, arousal and choice require normal levels of this neuromodulator. PMID:21187381
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Re-evaluation of the reward comparison hypothesis for alcohol abuse.
He, Alan Bo-Han; Chang, Yu-Chieh; Meng, Anna Wan Yun; Huang, Andrew Chih Wei
2017-08-14
This study examined whether various doses of ethanol induced reward or aversion and then evaluated Grigson's reward comparison hypothesis (1997). Rats were given a 0.1% saccharin solution (conditioned stimulus 1 [CS1]) 15min prior to administration of a 0, 0.05, 0.125, 0.20, 0.35, or 0.50g/kg dose of ethanol (unconditioned stimulus [US]). The rats were then exposed to a paired compartment (CS2) for 30min. The low dose of 0.05g/kg ethanol did not induce conditioned suppression (i.e., conditioned taste aversion [CTA]) or conditioned place preference (CPP). The dose of 0.125g/kg ethanol induced CPP but not CTA. High doses of ethanol, including 0.35g/kg and 0.50g/kg, produced CTA but not CPP. The middle dose of 0.20g/kg ethanol simultaneously induced CTA and CPP. As a result, the reward comparison hypothesis cannot explain the present finding that the middle dose of ethanol induced CTA and CPP. Meanwhile, the high doses of ethanol induced motivationally aversive CTA but not rewarding CPP. The reward comparison hypothesis should be updated further. Copyright © 2017 Elsevier B.V. All rights reserved.
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Lemay, Francis; Doré, François Y; Beaulieu, Jean-Martin
2015-11-16
Polymorphisms in the gene encoding the brain serotonin synthesis enzyme Tph2 have been identified in mental illnesses, with co-morbidity of substance use disorder. However, little is known about the impact of Tph2 gene variants on addiction. Mice expressing a human Tph2 loss of function variant were used to investigate consequences of aversive conditions on ethanol intake. Mice were familiarized either with ethanol or a solution containing both ethanol and the bittering agent quinine. Effect of familiarization to ethanol or an ethanol-quinine solution was then evaluated using a two-bottles preference test in Tph2-KI and control littermates. Mice from both genotypes displayed similar levels of ethanol consumption and quinine avoidance when habituated to ethanol alone. In contrast, addition of quinine to ethanol during the familiarization period resulted in a reduction of avoidance for the quinine-ethanol solution only in mutant mice. These results indicate that loss of function mutation in Tph2 results in greater motivation for ethanol consumption under aversive conditions and may confer enhanced sensitivity to alcohol use disorder. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Battjes-Fries, Marieke C E; Haveman-Nies, Annemien; Zeinstra, Gertrude G; van Dongen, Ellen J I; Meester, Hante J; van den Top-Pullen, Rinelle; Van't Veer, Pieter; de Graaf, Kees
2017-02-01
This study assessed the effectiveness of the Dutch school programme Taste Lessons with and without additional experiential learning activities on children's willingness to taste unfamiliar vegetables. Thirty-three primary schools (877 children in grades 6-7 with a mean age of 10.3 years) participated in Taste Lessons Vegetable Menu (TLVM, lessons and extra activities), Taste Lessons (TL, lessons), or a control group. A baseline and follow-up measurement was used to assess for each child: number of four familiar and four unfamiliar vegetables tasted, quantity tasted, choice of vegetable of which to eat more, and number of vegetables willing to taste again later. Furthermore, children filled out a questionnaire on daily vegetable intake and food neophobia. Multilevel and Cox regression analyses were conducted to compare changes in the outcome measures between the three study groups. No significant intervention effects were found on willingness to taste unfamiliar vegetables. Neither were effects found on familiar vegetables, except for number of familiar vegetables tasted (p < 0.05). Furthermore, no significant intervention effects were found on daily vegetable consumption and food neophobia. These results indicate that more intensive school-based nutrition education activities are needed to increase children's willingness to taste unfamiliar vegetables and increase their vegetable intake. Copyright © 2016. Published by Elsevier Ltd.
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Distinct circuits for the formation and retrieval of an imprinted olfactory memory
Jin, Xin; Pokala, Navin; Bargmann, Cornelia I.
2016-01-01
Summary Memories formed early in life are particularly stable and influential, representing privileged experiences that shape enduring behaviors. Here we show that exposing newly-hatched C. elegans to pathogenic bacteria results in persistent aversion to those bacterial odors, whereas adult exposure generates only transient aversive memory. Long-lasting imprinted aversion has a critical period in the first larval stage, and is specific to the experienced pathogen. Distinct groups of neurons are required during formation (AIB, RIM) and retrieval (AIY, RIA) of the imprinted memory. RIM synthesizes the neuromodulator tyramine, which is required in the L1 stage for learning. AIY memory retrieval neurons sense tyramine via the SER-2 receptor, which is essential for imprinted but not for adult-learned aversion. Odor responses in several neurons, most notably RIA, are altered in imprinted animals. These findings provide insight into neuronal substrates of different forms of memory, and lay a foundation for further understanding of early learning. PMID:26871629
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Learning shapes the aversion and reward responses of lateral habenula neurons
Wang, Daqing; Li, Yi; Feng, Qiru; Guo, Qingchun; Zhou, Jingfeng; Luo, Minmin
2017-01-01
The lateral habenula (LHb) is believed to encode negative motivational values. It remains unknown how LHb neurons respond to various stressors and how learning shapes their responses. Here, we used fiber-photometry and electrophysiology to track LHb neuronal activity in freely-behaving mice. Bitterness, pain, and social attack by aggressors intensively excite LHb neurons. Aversive Pavlovian conditioning induced activation by the aversion-predicting cue in a few trials. The experience of social defeat also conditioned excitatory responses to previously neutral social stimuli. In contrast, fiber photometry and single-unit recordings revealed that sucrose reward inhibited LHb neurons and often produced excitatory rebound. It required prolonged conditioning and high reward probability to induce inhibition by reward-predicting cues. Therefore, LHb neurons can bidirectionally process a diverse array of aversive and reward signals. Importantly, their responses are dynamically shaped by learning, suggesting that the LHb participates in experience-dependent selection of behavioral responses to stressors and rewards. DOI: http://dx.doi.org/10.7554/eLife.23045.001 PMID:28561735
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Developmentally defined forebrain circuits regulate appetitive and aversive olfactory learning.
Muthusamy, Nagendran; Zhang, Xuying; Johnson, Caroline A; Yadav, Prem N; Ghashghaei, H Troy
2017-01-01
Postnatal and adult neurogenesis are region- and modality-specific, but the significance of developmentally distinct neuronal populations remains unclear. We demonstrate that chemogenetic inactivation of a subset of forebrain and olfactory neurons generated at birth disrupts responses to an aversive odor. In contrast, novel appetitive odor learning is sensitive to inactivation of adult-born neurons, revealing that developmentally defined sets of neurons may differentially participate in hedonic aspects of sensory learning.
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Aversive learning of odor-heat associations in ants.
Desmedt, Lucie; Baracchi, David; Devaud, Jean-Marc; Giurfa, Martin; d'Ettorre, Patrizia
2017-12-15
Ants have recently emerged as useful models for the study of olfactory learning. In this framework, the development of a protocol for the appetitive conditioning of the maxilla-labium extension response (MaLER) provided the possibility of studying Pavlovian odor-food learning in a controlled environment. Here we extend these studies by introducing the first Pavlovian aversive learning protocol for harnessed ants in the laboratory. We worked with carpenter ants Camponotus aethiops and first determined the capacity of different temperatures applied to the body surface to elicit the typical aversive mandible opening response (MOR). We determined that 75°C is the optimal temperature to induce MOR and chose the hind legs as the stimulated body region because of their high sensitivity. We then studied the ability of ants to learn and remember odor-heat associations using 75°C as the unconditioned stimulus. We studied learning and short-term retention after absolute (one odor paired with heat) and differential conditioning (a punished odor versus an unpunished odor). Our results show that ants successfully learn the odor-heat association under a differential-conditioning regime and thus exhibit a conditioned MOR to the punished odor. Yet, their performance under an absolute-conditioning regime is poor. These results demonstrate that ants are capable of aversive learning and confirm previous findings about the different attentional resources solicited by differential and absolute conditioning in general. © 2017. Published by The Company of Biologists Ltd.
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Perception of sweet taste is important for voluntary alcohol consumption in mice.
Blednov, Y A; Walker, D; Martinez, M; Levine, M; Damak, S; Margolskee, R F
2008-02-01
To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.
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Genomic, genetic and functional dissection of bitter taste responses to artificial sweeteners.
Roudnitzky, Natacha; Bufe, Bernd; Thalmann, Sophie; Kuhn, Christina; Gunn, Howard C; Xing, Chao; Crider, Bill P; Behrens, Maik; Meyerhof, Wolfgang; Wooding, Stephen P
2011-09-01
Bitter taste perception is initiated by TAS2R receptors, which respond to agonists by triggering depolarization of taste bud cells. Mutations in TAS2Rs are known to affect taste phenotypes by altering receptor function. Evidence that TAS2Rs overlap in ligand specificity suggests that they may also contribute joint effects. To explore this aspect of gustation, we examined bitter perception of saccharin and acesulfame K, widely used artificial sweeteners with aversive aftertastes. Both substances are agonists of TAS2R31 and -43, which belong to a five-member subfamily (TAS2R30-46) responsive to a diverse constellation of compounds. We analyzed sequence variation and linkage structure in the ∼140 kb genomic region encoding TAS2R30-46, taste responses to the two sweeteners in subjects, and functional characteristics of receptor alleles. Whole-gene sequences from TAS2R30-46 in 60 Caucasian subjects revealed extensive diversity including 34 missense mutations, two nonsense mutations and high-frequency copy-number variants. Thirty markers, including non-synonymous variants in all five genes, were associated (P< 0.001) with responses to saccharin and acesulfame K. However, linkage disequilibrium (LD) in the region was high (D', r(2) > 0.95). Haplotype analyses revealed that most associations were spurious, arising from LD with variants in TAS2R31. In vitro assays confirmed the functional importance of four TAS2R31 mutations, which had independent effects on receptor response. The existence of high LD spanning functionally distinct TAS2R loci predicts that bitter taste responses to many compounds will be strongly correlated even when they are mediated by different genes. Integrative approaches combining phenotypic, genetic and functional analysis will be essential in dissecting these complex relationships.
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Wilbertz, Gregor; Sterzer, Philipp
2018-05-01
Alternating conscious visual perception of bistable stimuli is influenced by several factors. In order to understand the effect of negative valence, we tested the effect of two types of aversive conditioning on dominance durations in binocular rivalry. Participants received either aversive classical conditioning of the stimuli shown alone between rivalry blocks, or aversive percept conditioning of one of the two possible perceptual choices during rivalry. Both groups showed successful aversive conditioning according to skin conductance responses and affective valence ratings. However, while classical conditioning led to an immediate but short-lived increase in dominance durations of the conditioned stimulus, percept conditioning yielded no significant immediate effect but tended to decrease durations of the conditioned percept during extinction. These results show dissociable effects of value learning on perceptual inference in situations of perceptual conflict, depending on whether learning relates to the decision between conflicting perceptual choices or the sensory stimuli per se. Copyright © 2018 Elsevier Inc. All rights reserved.
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Reappraising social insect behavior through aversive responsiveness and learning.
Roussel, Edith; Carcaud, Julie; Sandoz, Jean-Christophe; Giurfa, Martin
2009-01-01
The success of social insects can be in part attributed to their division of labor, which has been explained by a response threshold model. This model posits that individuals differ in their response thresholds to task-associated stimuli, so that individuals with lower thresholds specialize in this task. This model is at odds with findings on honeybee behavior as nectar and pollen foragers exhibit different responsiveness to sucrose, with nectar foragers having higher response thresholds to sucrose concentration. Moreover, it has been suggested that sucrose responsiveness correlates with responsiveness to most if not all other stimuli. If this is the case, explaining task specialization and the origins of division of labor on the basis of differences in response thresholds is difficult. To compare responsiveness to stimuli presenting clear-cut differences in hedonic value and behavioral contexts, we measured appetitive and aversive responsiveness in the same bees in the laboratory. We quantified proboscis extension responses to increasing sucrose concentrations and sting extension responses to electric shocks of increasing voltage. We analyzed the relationship between aversive responsiveness and aversive olfactory conditioning of the sting extension reflex, and determined how this relationship relates to division of labor. Sucrose and shock responsiveness measured in the same bees did not correlate, thus suggesting that they correspond to independent behavioral syndromes, a foraging and a defensive one. Bees which were more responsive to shock learned and memorized better aversive associations. Finally, guards were less responsive than nectar foragers to electric shocks, exhibiting higher tolerance to low voltage shocks. Consequently, foragers, which are more sensitive, were the ones learning and memorizing better in aversive conditioning. Our results constitute the first integrative study on how aversive responsiveness affects learning, memory and social organization in honeybees. We suggest that parallel behavioral modules (e.g. appetitive, aversive) coexist within each individual bee and determine its tendency to adopt a given task. This conclusion, which is at odds with a simple threshold model, should open new opportunities for exploring the division of labor in social insects.
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Development switch in neural circuitry underlying odor-malaise learning.
Shionoya, Kiseko; Moriceau, Stephanie; Lunday, Lauren; Miner, Cathrine; Roth, Tania L; Sullivan, Regina M
2006-01-01
Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.
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Physical Approaches to Masking Bitter Taste: Lessons from Food and Pharmaceuticals
Hayes, John E.
2016-01-01
Many drugs and desirable phytochemicals are bitter, and bitter tastes are aversive. Food and pharmaceutical manufacturers share a common need for bitterness-masking strategies that allow them to deliver useful quantities of the active compounds in an acceptable form and in this review we compare and contrast the challenges and approaches by researchers in both fields. We focus on physical approaches, i.e., micro- or nano-structures to bind bitter compounds in the mouth, yet break down to allow release after they are swallowed. In all of these methods, the assumption is the degree of bitterness suppression depends on the concentration of bitterant in the saliva and hence the proportion that is bound. Surprisingly, this hypothesis has only rarely been fully tested using a combination of adequate human sensory trials and measurements of binding. This is especially true in pharmaceutical systems, perhaps due to the greater experimental challenges in sensory analysis of drugs. PMID:25205460
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Role for the rostromedial tegmental nucleus in signaling the aversive properties of alcohol
Glover, Elizabeth J.; McDougle, Molly J.; Siegel, Griffin S.; Jhou, Thomas C.; Chandler, L. Judson
2016-01-01
Background While the rewarding effects of alcohol contribute significantly to its addictive potential, it is becoming increasingly appreciated that alcohol’s aversive properties also play an important role in the propensity to drink. Despite this, the neurobiological mechanism for alcohol’s aversive actions is not well understood. The rostromedial tegmental nucleus (RMTg) was recently characterized for its involvement in aversive signaling and has been shown to encode the aversive properties of cocaine, yet its involvement in alcohol’s aversive actions have not been elucidated. Methods Adult male and female Long-Evans rats underwent conditioned taste aversion (CTA) procedures where exposure to a novel saccharin solution was paired with i.p. administration of saline, lithium chloride (LiCl), or ethanol (EtOH). Control rats underwent the same paradigm except that drug and saccharin exposure were explicitly unpaired. Saccharin consumption was measured on test day in the absence of drug administration and rats were sacrificed 90–105 min following access to saccharin. Brains were subsequently harvested and processed for cFos immunohistochemistry. The number of cFos labeled neurons was counted in the RMTg and the lateral habenula (LHb) – a region that sends prominent glutamatergic input to the RMTg. Results In rats that received paired drug and saccharin exposure, EtOH and LiCl induced significant CTA compared to saline to a similar degree in males and females. Both EtOH- and LiCl-induced CTA significantly enhanced cFos expression in the RMTg and LHb but not the hippocampus. Similar to behavioral measures, no significant effect of sex on CTA-induced cFos expression was observed. cFos expression in both the RMTg and LHb was significantly correlated to CTA magnitude with greater cFos being associated with more pronounced CTA. In addition, cFos expression in the RMTg was positively correlated with LHb cFos. Conclusions These data suggest that the RMTg and LHb are involved in the expression of CTA and are consistent with previous work implicating the RMTg in aversive signaling. Furthermore, increased cFos expression in the RMTg following EtOH-induced CTA suggests that this region plays a role in signaling alcohol’s aversive properties. PMID:27388762
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Motor coordination defects in mice deficient for the Sam68 RNA-binding protein.
Lukong, Kiven E; Richard, Stéphane
2008-06-03
The role of RNA-binding proteins in the central nervous system and more specifically their role in motor coordination and learning are poorly understood. We previously reported that ablation of RNA-binding protein Sam68 in mice results in male sterility and delayed mammary gland development and protection against osteoporosis in females. Sam68 however is highly expressed in most regions of the brain especially the cerebellum and thus we investigated the cerebellar-related manifestations in Sam68-null mice. We analyzed the mice for motor function, sensory function, and learning and memory abilities. Herein, we report that Sam68-null mice have motor coordination defects as assessed by beam walking and rotorod performance. Forty-week-old Sam68-null mice (n=12) were compared to their wild-type littermates (n=12). The Sam68-null mice exhibited more hindpaw faults in beam walking tests and fell from the rotating drum at lower speeds and prematurely compared to the wild-type controls. The Sam68-null mice were, however, normal for forelimb strength, tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion. Our findings support a role for Sam68 in the central nervous system in the regulation of motor coordination.
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ERIC Educational Resources Information Center
Sangha, Susan; Ilenseer, Jasmin; Sosulina, Ludmila; Lesting, Jorg; Pape, Hans-Christian
2012-01-01
Extinction reduces fear to stimuli that were once associated with an aversive event by no longer coupling the stimulus with the aversive event. Extinction learning is supported by a network comprising the amygdala, hippocampus, and prefrontal cortex. Previous studies implicate a critical role of GABA in extinction learning, specifically the GAD65…
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ERIC Educational Resources Information Center
Richlitzki, Antje; Latour, Philipp; Schwärzel, Martin
2017-01-01
Here, we define a role of the cAMP intermediate EPAC in "Drosophila" aversive odor learning by means of null epac mutants. Complementation analysis revealed that EPAC acts downstream from the "rutabaga" adenylyl cyclase and in parallel to protein kinase A. By means of targeted knockdown and genetic rescue we identified mushroom…
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Ethanol, saccharin, and quinine: early ontogeny of taste responsiveness and intake.
Kozlov, Andrey P; Varlinskaya, Elena I; Spear, Norman E
2008-02-01
Rat pups demonstrate high levels of immediate acceptance of ethanol during the first 2 weeks of postnatal life. Given that the taste of ethanol is most likely perceived by infant rats as a combination of sweet and bitter, high intake of ethanol early in ontogeny may be associated with age-related enhanced responsiveness to the sweet component of ethanol taste, as well as with ontogenetic decreases in sensitivity to its bitter component. Therefore, the present study compared responsiveness to ethanol and solutions with bitter (quinine) and sweet (saccharin) taste in terms of intake and palatability across the first 2 weeks of postnatal life. Characteristic patterns of responsiveness to 10% (v/v) ethanol, 0.1% saccharin, 0.2% quinine, and water in terms of taste reactivity and fluid intake were assessed in rat pups tested on postnatal day (P) 4, 9, or 12 using a new technique of on-line monitoring of fluid flow through a two-channel intraoral cannula. Taste reactivity included analysis of ingestive and aversive responses following six intraoral infusions of the test fluids. This taste reactivity probe was followed by the intake test, in which animals were allowed to voluntarily ingest fluids from an intraoral cannula. Pups of all ages showed more appetitive responses to saccharin and ethanol than to water or quinine. No age-related differences were apparent in taste responsiveness to saccharin and ethanol. However, the age-related pattern of ethanol intake drastically differed from that of saccharin. Intake of saccharin increased from P4 to P9 and decreased substantially by P12, whereas intake of ethanol gradually increased from P4 to P12. Intake of ethanol was significantly lower than intake of saccharin on P9, whereas P12 pups took in more ethanol than saccharin. The findings of the present study indicate ontogenetic dissociations between taste reactivity to ethanol and saccharin and intake of these solutions, and suggest that high acceptance of ethanol early in ontogeny may not be associated with its orosensory properties but rather with the pharmacological effects of ethanol.
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Perceived ambiguity as a barrier to intentions to learn genome sequencing results.
Taber, Jennifer M; Klein, William M P; Ferrer, Rebecca A; Han, Paul K J; Lewis, Katie L; Biesecker, Leslie G; Biesecker, Barbara B
2015-10-01
Many variants that could be returned from genome sequencing may be perceived as ambiguous-lacking reliability, credibility, or adequacy. Little is known about how perceived ambiguity influences thoughts about sequencing results. Participants (n = 494) in an NIH genome sequencing study completed a baseline survey before sequencing results were available. We examined how perceived ambiguity regarding sequencing results and individual differences in medical ambiguity aversion and tolerance for uncertainty were associated with cognitions and intentions concerning sequencing results. Perceiving sequencing results as more ambiguous was associated with less favorable cognitions about results and lower intentions to learn and share results. Among participants low in tolerance for uncertainty or optimism, greater perceived ambiguity was associated with lower intentions to learn results for non-medically actionable diseases; medical ambiguity aversion did not moderate any associations. Results are consistent with the phenomenon of "ambiguity aversion" and may influence whether people learn and communicate genomic information.
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Mizunami, Makoto; Matsumoto, Yukihisa
2017-01-01
Revealing neural systems that mediate appetite and aversive signals in associative learning is critical for understanding the brain mechanisms controlling adaptive behavior in animals. In mammals, it has been shown that some classes of dopamine neurons in the midbrain mediate prediction error signals that govern the learning process, whereas other classes of dopamine neurons control execution of learned actions. In this review, based on the results of our studies on Pavlovian conditioning in the cricket Gryllus bimaculatus and by referring to the findings in honey bees and fruit-flies, we argue that comparable aminergic systems exist in the insect brain. We found that administrations of octopamine (the invertebrate counterpart of noradrenaline) and dopamine receptor antagonists impair conditioning to associate an olfactory or visual conditioned stimulus (CS) with water or sodium chloride solution (appetitive or aversive unconditioned stimulus, US), respectively, suggesting that specific octopamine and dopamine neurons mediate appetitive and aversive signals, respectively, in conditioning in crickets. These findings differ from findings in fruit-flies. In fruit-flies, appetitive and aversive signals are mediated by different dopamine neuron subsets, suggesting diversity in neurotransmitters mediating appetitive signals in insects. We also found evidences of “blocking” and “auto-blocking” phenomena, which suggested that the prediction error, the discrepancy between actual US and predicted US, governs the conditioning in crickets and that octopamine neurons mediate prediction error signals for appetitive US. Our studies also showed that activations of octopamine and dopamine neurons are needed for the execution of an appetitive conditioned response (CR) and an aversive CR, respectively, and we, thus, proposed that these neurons mediate US prediction signals that drive appetitive and aversive CRs. Our findings suggest that the basic principles of functioning of aminergic systems in associative learning, i.e., to transmit prediction error signals for conditioning and to convey US prediction signals for execution of CR, are conserved among insects and mammals, on account of the fact that the organization of the insect brain is much simpler than that of the mammalian brain. Further investigation of aminergic systems that govern associative learning in insects should lead to a better understanding of commonalities and diversities of computational rules underlying associative learning in animals. PMID:29311961
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Mizunami, Makoto; Matsumoto, Yukihisa
2017-01-01
Revealing neural systems that mediate appetite and aversive signals in associative learning is critical for understanding the brain mechanisms controlling adaptive behavior in animals. In mammals, it has been shown that some classes of dopamine neurons in the midbrain mediate prediction error signals that govern the learning process, whereas other classes of dopamine neurons control execution of learned actions. In this review, based on the results of our studies on Pavlovian conditioning in the cricket Gryllus bimaculatus and by referring to the findings in honey bees and fruit-flies, we argue that comparable aminergic systems exist in the insect brain. We found that administrations of octopamine (the invertebrate counterpart of noradrenaline) and dopamine receptor antagonists impair conditioning to associate an olfactory or visual conditioned stimulus (CS) with water or sodium chloride solution (appetitive or aversive unconditioned stimulus, US), respectively, suggesting that specific octopamine and dopamine neurons mediate appetitive and aversive signals, respectively, in conditioning in crickets. These findings differ from findings in fruit-flies. In fruit-flies, appetitive and aversive signals are mediated by different dopamine neuron subsets, suggesting diversity in neurotransmitters mediating appetitive signals in insects. We also found evidences of "blocking" and "auto-blocking" phenomena, which suggested that the prediction error, the discrepancy between actual US and predicted US, governs the conditioning in crickets and that octopamine neurons mediate prediction error signals for appetitive US. Our studies also showed that activations of octopamine and dopamine neurons are needed for the execution of an appetitive conditioned response (CR) and an aversive CR, respectively, and we, thus, proposed that these neurons mediate US prediction signals that drive appetitive and aversive CRs. Our findings suggest that the basic principles of functioning of aminergic systems in associative learning, i.e., to transmit prediction error signals for conditioning and to convey US prediction signals for execution of CR, are conserved among insects and mammals, on account of the fact that the organization of the insect brain is much simpler than that of the mammalian brain. Further investigation of aminergic systems that govern associative learning in insects should lead to a better understanding of commonalities and diversities of computational rules underlying associative learning in animals.
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Nagai, Masanori; Matsumoto, Sayaka; Endo, Junko; Sakamoto, Reiko; Wada, Maki
2015-03-15
Influences of depression symptoms on the sweet taste threshold were investigated in healthy college students (30 males and 40 females). Depression symptoms were scored by SDS (Self-Rating Depression Scale), and anxiety levels by STAI (State- and Trait-Anxiety Inventory). Recognition thresholds for sucrose were determined. In female students, the menstrual phase on the day of the experiment was self-reported. Depression symptoms, anxiety levels, and the recognition threshold for sucrose were not different among the 3 groups, i.e. males, females in the follicular phase, and females in the luteal phase. Depression symptoms were positively correlated with state and trait anxiety in all groups. The sweet taste threshold was inversely correlated with depression symptoms (r=-0.472, p=0.031) and trait anxiety (r=-0.506, p=0.019) in females in the luteal phase. In males as well as females in the follicular phase, however, no correlation between sweet taste threshold and depression was found. The results show that the recognition threshold for sucrose reduces with increased depression in females with a higher anxiety trait, but only in the luteal phase. It is hypothesized that brain regions, which spatially overlap and are responsible for both aversive emotions and gustatory processing, are susceptible to periodic changes in gonadal hormones due to the menstrual cycle. Copyright © 2015 Elsevier Inc. All rights reserved.
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Ancel, Déborah; Bernard, Arnaud; Subramaniam, Selvakumar; Hirasawa, Akira; Tsujimoto, Gozoh; Hashimoto, Toshihiro; Passilly-Degrace, Patricia; Khan, Naim-Akhtar; Besnard, Philippe
2015-02-01
Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the "taste of fat", the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological [i.e., immunohistochemical staining of circumvallate papillae (CVP)], behavioral (i.e., two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies [i.e., calcium imaging in freshly isolated taste bud cells (TBCs)], we show that absence of GPR120 in the oral cavity was not associated with changes in i) gross anatomy of CVP, ii) LCFA-mediated increases in intracellular calcium levels ([Ca(2+)]i), iii) preference for oily and LCFA solutions and iv) conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca(2+)]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking. Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.
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Torregrossa, A-M; Loney, G C; Smith, J C; Eckel, L A
2015-03-01
Sucralose avoiding rats detect a bitter-like taste quality in concentrations of sucralose that are strongly preferred over water by sucralose preferring rats. Here, we investigated whether sucralose preferrers (SP) also detect a bitter-like quality in sucralose that may be masked by an increased perception of sucralose's sweet-like quality. A microstructural analysis of sucralose intake revealed that, at concentrations they avoided in preference tests, sucralose avoiders (SA) consumed smaller and fewer bouts of sucralose than SP. Interestingly, the concentration-dependent increase in sucralose preference in SP was not associated with larger bouts or increased lick rate, two measures that are expected to increase with increasing perceived sweetness. This suggests that SP can detect an aversive quality in sucralose, but this perception of a presumably bitter-like quality may be masked by increased salience of a sweet-like quality that sustains high levels of intake in SP. Further evidence for increased sweet-taste perception in SP, relative to SA, was obtained in a second study in which SP consumed more of a palatable sweet-milk diet than SA. These are the first data to suggest that SP are not blind to the bitter-like quality in sucralose, and that there may be differences in sweet-taste perception between SP and SA. Copyright © 2014 Elsevier Inc. All rights reserved.
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RSK2 Signaling in Brain Habenula Contributes to Place Aversion Learning
ERIC Educational Resources Information Center
Darcq, Emmanuel; Koebel, Pascale; Del Boca, Carolina; Pannetier, Solange; Kirstetter, Anne-Sophie; Garnier, Jean-Marie; Hanauer, Andre; Befort, Katia; Kieffer, Brigitte L.
2011-01-01
RSK2 is a Ser/Thr kinase acting in the Ras/MAPK pathway. "Rsk2" gene deficiency leads to the Coffin-Lowry Syndrome, notably characterized by cognitive deficits. We found that "mrsk2" knockout mice are unable to associate an aversive stimulus with context in a lithium-induced conditioned place aversion task requiring both high-order cognition and…
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PRENATAL ETHANOL EXPOSURE LEADS TO GREATER ETHANOL-INDUCED APPETITIVE REINFORCEMENT
Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.
2012-01-01
Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30–45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance. PMID:22698870
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Extinction, Spontaneous Recovery and Renewal of Flavor Preferences Based on Taste-Taste Learning
ERIC Educational Resources Information Center
Diaz, Estrella; De la Casa, L. G.
2011-01-01
This paper presents evidence of extinction, spontaneous recovery and renewal in a conditioned preferences paradigm based on taste-taste associations. More specifically, in three experiments rats exposed to a simultaneous compound of citric acid-saccharin solution showed a preference for the citric solution when the preference was measured with a…
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Alterations of sucrose preference after Roux-en-Y gastric bypass.
Bueter, M; Miras, A D; Chichger, H; Fenske, W; Ghatei, M A; Bloom, S R; Unwin, R J; Lutz, T A; Spector, A C; le Roux, C W
2011-10-24
Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as "just about right" pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p<0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p=0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p<0.05), but both groups considered the same sucrose concentration as "just about right" postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass. Copyright © 2011 Elsevier Inc. All rights reserved.
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IntelliCages and automated assessment of learning in group-housed mice
NASA Astrophysics Data System (ADS)
Puścian, Alicja; Knapska, Ewelina
2014-11-01
IntelliCage is a fully automated, computer controlled system, which can be used for long-term monitoring of behavior of group-housed mice. Using standardized experimental protocols we can assess cognitive abilities and behavioral flexibility in appetitively and aversively motivated tasks, as well as measure social influences on learning of the subjects. We have also identified groups of neurons specifically activated by appetitively and aversively motivated learning within the amygdala, function of which we are going to investigate optogenetically in the future.
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Why do women stop smoking during pregnancy? Cigarettes taste and smell bad.
Pletsch, Pamela K; Kratz, Anna Thornton
2004-08-01
There are high rates of cigarette smoking resumption among women who have quit smoking while pregnant, and the reasons for this are poorly understood. Our purpose in this study was to obtain an in-depth description of the context surrounding smoking behaviors during pregnancy and the first 3 months after women give birth in order to gain insight into the reasons women resume smoking. We used a longitudinal qualitative descriptive approach with in-depth interviews conducted early in pregnancy, at 36 weeks of pregnancy, and 3 months postpartum. Our purposive sample consisted of 15 pregnant women who had stopped smoking without assistance by their first prenatal visit. All women smoked mentholated cigarettes prior to pregnancy and 40% were primiparas. A thematic content analysis of 43 interviews revealed that the majority of women experienced an aversion to the taste or smell of tobacco smoke while pregnant and attributed these sensation changes to being pregnant. The taste and smell of tobacco smoke returned to prepregnancy states postpartum, and by 3 months postpartum 73% of the women had resumed smoking. This physiologic change can be conceptualized as a pregnancy-specific motivation for smoking cessation that can inform our efforts toward relapse prevention.
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Deckmann, Klaus; Filipski, Katharina; Krasteva-Christ, Gabriela; Fronius, Martin; Althaus, Mike; Rafiq, Amir; Papadakis, Tamara; Renno, Liane; Jurastow, Innokentij; Wessels, Lars; Wolff, Miriam; Schütz, Burkhard; Weihe, Eberhard; Chubanov, Vladimir; Gudermann, Thomas; Klein, Jochen; Bschleipfer, Thomas; Kummer, Wolfgang
2014-06-03
Chemosensory cells in the mucosal surface of the respiratory tract ("brush cells") use the canonical taste transduction cascade to detect potentially hazardous content and trigger local protective and aversive respiratory reflexes on stimulation. So far, the urogenital tract has been considered to lack this cell type. Here we report the presence of a previously unidentified cholinergic, polymodal chemosensory cell in the mammalian urethra, the potential portal of entry for bacteria and harmful substances into the urogenital system, but not in further centrally located parts of the urinary tract, such as the bladder, ureter, and renal pelvis. Urethral brush cells express bitter and umami taste receptors and downstream components of the taste transduction cascade; respond to stimulation with bitter (denatonium), umami (monosodium glutamate), and uropathogenic Escherichia coli; and release acetylcholine to communicate with other cells. They are approached by sensory nerve fibers expressing nicotinic acetylcholine receptors, and intraurethral application of denatonium reflexively increases activity of the bladder detrusor muscle in anesthetized rats. We propose a concept of urinary bladder control involving a previously unidentified cholinergic chemosensory cell monitoring the chemical composition of the urethral luminal microenvironment for potential hazardous content.
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Perisse, Emmanuel; Owald, David; Barnstedt, Oliver; Talbot, Clifford B; Huetteroth, Wolf; Waddell, Scott
2016-06-01
In Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom body output neuron (MBON)-γ1pedc>α/β. However, MVP2 neuron output is only essential for expression of short-term aversive memory. Stimulating MVP2 neurons preferentially inhibits the odor-evoked activity of avoidance-directing MBONs and odor-driven avoidance behavior, whereas their inhibition enhances odor avoidance. In contrast, odor-evoked activity of MVP2 neurons is elevated in hungry flies, and their feed-forward inhibition is required for expression of appetitive memory at all times. Moreover, imposing MVP2 activity promotes inappropriate appetitive memory expression in food-satiated flies. Aversive learning and appetitive motivation therefore toggle alternate modes of a common feed-forward inhibitory MVP2 pathway to promote conditioned odor avoidance or approach. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
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Motivational state controls the prediction error in Pavlovian appetitive-aversive interactions.
Laurent, Vincent; Balleine, Bernard W; Westbrook, R Frederick
2018-01-01
Contemporary theories of learning emphasize the role of a prediction error signal in driving learning, but the nature of this signal remains hotly debated. Here, we used Pavlovian conditioning in rats to investigate whether primary motivational and emotional states interact to control prediction error. We initially generated cues that positively or negatively predicted an appetitive food outcome. We then assessed how these cues modulated aversive conditioning when a novel cue was paired with a foot shock. We found that a positive predictor of food enhances, whereas a negative predictor of that same food impairs, aversive conditioning. Critically, we also showed that the enhancement produced by the positive predictor is removed by reducing the value of its associated food. In contrast, the impairment triggered by the negative predictor remains insensitive to devaluation of its associated food. These findings provide compelling evidence that the motivational value attributed to a predicted food outcome can directly control appetitive-aversive interactions and, therefore, that motivational processes can modulate emotional processes to generate the final error term on which subsequent learning is based. Copyright © 2017 Elsevier Inc. All rights reserved.
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The Development and Public Health Implications of Food Preferences in Children
Beckerman, Jacob P.; Alike, Queen; Lovin, Erika; Tamez, Martha; Mattei, Josiemer
2017-01-01
Food preferences are a primary determinant of dietary intake and behaviors, and they persist from early childhood into later life. As such, establishing preferences for healthy foods from a young age is a promising approach to improving diet quality, a leading contributor to cardiometabolic health. This narrative review first describes the critical period for food preference development starting in utero and continuing through early childhood. Infants’ innate aversion to sour and bitter tastes can lead them to initially reject some healthy foods such as vegetables. Infants can learn to like these foods through exposures to their flavors in utero and through breastmilk. As solid foods are introduced through toddlerhood, children’s food preferences are shaped by parent feeding practices and environmental factors such as food advertising. Next, we discuss two key focus areas to improve diet quality highlighted by the current understanding of food preferences: (1) promoting healthy food preferences through breastfeeding and early exposures to healthy foods and (2) limiting the extent to which innate preferences for sweet and salty tastes lead to poor diet quality. We use an ecological framework to summarize potential points of intervention and provide recommendations for these focus areas, such as worksite benefits that promote breastfeeding, and changes in food retail and service environments. Individuals’ choices around breastfeeding and diet may ultimately be influenced by policy and community-level factors. It is thus crucial to take a multilevel approach to establish healthy food preferences from a young age, which have the potential to translate into lifelong healthy diet. PMID:29326942
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The role of risk aversion in non-conscious decision making.
Wang, Shuo; Krajbich, Ian; Adolphs, Ralph; Tsuchiya, Naotsugu
2012-01-01
To what extent can people choose advantageously without knowing why they are making those choices? This hotly debated question has capitalized on the Iowa Gambling Task (IGT), in which people often learn to choose advantageously without appearing to know why. However, because the IGT is unconstrained in many respects, this finding remains debated and other interpretations are possible (e.g., risk aversion, ambiguity aversion, limits of working memory, or insensitivity to reward/punishment can explain the finding of the IGT). Here we devised an improved variant of the IGT in which the deck-payoff contingency switches after subjects repeatedly choose from a good deck, offering the statistical power of repeated within-subject measures based on learning the reward contingencies associated with each deck. We found that participants exhibited low confidence in their choices, as probed with post-decision wagering, despite high accuracy in selecting advantageous decks in the task, which is putative evidence for non-conscious decision making. However, such a behavioral dissociation could also be explained by risk aversion, a tendency to avoid risky decisions under uncertainty. By explicitly measuring risk aversion for each individual, we predicted subjects' post-decision wagering using Bayesian modeling. We found that risk aversion indeed does play a role, but that it did not explain the entire effect. Moreover, independently measured risk aversion was uncorrelated with risk aversion exhibited during our version of the IGT, raising the possibility that the latter risk aversion may be non-conscious. Our findings support the idea that people can make optimal choices without being fully aware of the basis of their decision. We suggest that non-conscious decision making may be mediated by emotional feelings of risk that are based on mechanisms distinct from those that support cognitive assessment of risk.
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The Role of Risk Aversion in Non-Conscious Decision Making
Wang, Shuo; Krajbich, Ian; Adolphs, Ralph; Tsuchiya, Naotsugu
2012-01-01
To what extent can people choose advantageously without knowing why they are making those choices? This hotly debated question has capitalized on the Iowa Gambling Task (IGT), in which people often learn to choose advantageously without appearing to know why. However, because the IGT is unconstrained in many respects, this finding remains debated and other interpretations are possible (e.g., risk aversion, ambiguity aversion, limits of working memory, or insensitivity to reward/punishment can explain the finding of the IGT). Here we devised an improved variant of the IGT in which the deck-payoff contingency switches after subjects repeatedly choose from a good deck, offering the statistical power of repeated within-subject measures based on learning the reward contingencies associated with each deck. We found that participants exhibited low confidence in their choices, as probed with post-decision wagering, despite high accuracy in selecting advantageous decks in the task, which is putative evidence for non-conscious decision making. However, such a behavioral dissociation could also be explained by risk aversion, a tendency to avoid risky decisions under uncertainty. By explicitly measuring risk aversion for each individual, we predicted subjects’ post-decision wagering using Bayesian modeling. We found that risk aversion indeed does play a role, but that it did not explain the entire effect. Moreover, independently measured risk aversion was uncorrelated with risk aversion exhibited during our version of the IGT, raising the possibility that the latter risk aversion may be non-conscious. Our findings support the idea that people can make optimal choices without being fully aware of the basis of their decision. We suggest that non-conscious decision making may be mediated by emotional feelings of risk that are based on mechanisms distinct from those that support cognitive assessment of risk. PMID:22375133
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Effects of loss aversion on neural responses to loss outcomes: An event-related potential study.
Kokmotou, Katerina; Cook, Stephanie; Xie, Yuxin; Wright, Hazel; Soto, Vicente; Fallon, Nicholas; Giesbrecht, Timo; Pantelous, Athanasios; Stancak, Andrej
2017-05-01
Loss aversion is the tendency to prefer avoiding losses over acquiring gains of the same amount. To shed light on the spatio-temporal processes underlying loss aversion, we analysed the associations between individual loss aversion and electrophysiological responses to loss and gain outcomes in a monetary gamble task. Electroencephalographic feedback-related negativity (FRN) was computed in 29 healthy participants as the difference in electrical potentials between losses and gains. Loss aversion was evaluated using non-linear parametric fitting of choices in a separate gamble task. Loss aversion correlated positively with FRN amplitude (233-263ms) at electrodes covering the lower face. Feedback related potentials were modelled by five equivalent source dipoles. From these dipoles, stronger activity in a source located in the orbitofrontal cortex was associated with loss aversion. The results suggest that loss aversion implemented during risky decision making is related to a valuation process in the orbitofrontal cortex, which manifests during learning choice outcomes. Copyright © 2017. Published by Elsevier B.V.
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Evolutionary Responses to Invasion: Cane Toad Sympatric Fish Show Enhanced Avoidance Learning
Caller, Georgina; Brown, Culum
2013-01-01
The introduced cane toad (Bufo marinus) poses a major threat to biodiversity due to its lifelong toxicity. Several terrestrial native Australian vertebrates are adapting to the cane toad’s presence and lab trials have demonstrated that repeated exposure to B. marinus can result in learnt avoidance behaviour. Here we investigated whether aversion learning is occurring in aquatic ecosystems by comparing cane toad naïve and sympatric populations of crimson spotted rainbow fish (Melanotaenia duboulayi). The first experiment indicated that fish from the sympatric population had pre-existing aversion to attacking cane toad tadpoles but also showed reduced attacks on native tadpoles. The second experiment revealed that fish from both naïve and sympatric populations learned to avoid cane toad tadpoles following repeated, direct exposure. Allopatric fish also developed a general aversion to tadpoles. The aversion learning abilities of both groups was examined using an experiment involving novel distasteful prey items. While both populations developed a general avoidance of edible pellets in the presence of distasteful pellets, only the sympatric population significantly reduced the number of attacks on the novel distasteful prey item. These results indicate that experience with toxic prey items over multiple generations can enhance avoidance leaning capabilities via natural selection. PMID:23372788
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Lesions of the lateral habenula facilitate active avoidance learning and threat extinction.
Song, Mihee; Jo, Yong Sang; Lee, Yeon-Kyung; Choi, June-Seek
2017-02-01
The lateral habenula (LHb) is an epithalamic brain structure that provides strong projections to midbrain monoaminergic systems that are involved in motivation, emotion, and reinforcement learning. LHb neurons are known to convey information about aversive outcomes and negative prediction errors, suggesting a role in learning from aversive events. To test this idea, we examined the effects of electrolytic lesions of the LHb on signaled two-way active avoidance learning in which rats were trained to avoid an unconditioned stimulus (US) by taking a proactive shuttling response to an auditory conditioned stimulus (CS). The lesioned animals learned the avoidance response significantly faster than the control groups. In a separate experiment, we also investigated whether the LHb contributes to Pavlovian threat (fear) conditioning and extinction. Following paired presentations of the CS and the US, LHb-lesioned animals showed normal acquisition of conditioned response (CR) measured with freezing. However, extinction of the CR in the subsequent CS-only session was significantly faster. The enhanced performance in avoidance learning and in threat extinction jointly suggests that the LHb normally plays an inhibitory role in learning driven by absence of aversive outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.
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Crowe, Simon F; Hale, Matthew W
2002-09-01
The single-trial passive avoidance task is a useful procedure for examining learning and memory in the young chick. However, it has recently been suggested that discrepant results reported by different laboratories are due to differences in training procedure. The present study investigated a number of parameters surrounding the passive avoidance task, using day-old White Leghorn, Black Australorp cockerels. The results suggested that presentation of a water-dipped bead immediately after the aversive bead significantly altered retention levels. In addition, when the water-dipped bead was presented after the aversive bead, chicks failed to discriminate between beads for a period of 10 min following exposure to the aversant experience. A novel variant of the passive avoidance procedure, involving pretraining with a water-dipped red bead, training with an aversant-coated red bead, and testing with a dry red bead, was evaluated. A measure of avoidance was calculated using all three trials. It is suggested that the use of a single bead, measured both before and after the training experience and using both aversant- and water-trained controls, results in the most concise characterization of memory-related phenomena in the chick which is not contaminated by a carryover effect from the aversive training experience to the nonaversive bead.
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Spector, Alan C.; le Roux, Carel W; Munger, Steven D.; Travers, Susan P.; Sclafani, Anthony; Mennella, Julie A.
2016-01-01
This paper summarizes research findings from six experts in the field of taste and feeding that were presented at the 2015 ASPEN Research Workshop. The theme was focused on the interaction of taste signals with those of a postingestive origin and how this contributes to regulation of food intake through both physiological and learning processes. Gastric bypass results in exceptional loss of fat mass, increases in circulating levels of key gut peptides, some of which are also expressed along with their cognate receptors in taste buds. Changes in taste preference and food selection in both bariatric surgery patients and rodent models have been reported. Accordingly, the effects of this surgery on taste-related behavior were examined. The conservation of receptor and peptide signaling mechanisms in gustatory and extraoral tissues was discussed in the context of taste responsiveness and the regulation of metabolism. New findings detailing the features of neural circuits between the caudal nucleus of the solitary tract (NST), receiving visceral input from the vagus nerve, and the rostral NST, receiving taste input, were discussed, as was how early life experience with taste stimuli and learned associations between flavor and postoral consequences of nutrients can exert potent and long-lasting effects on feeding PMID:26598504
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Aversive aftertaste changes visual food cue reactivity: An fMRI study on cross-modal perception.
Wabnegger, Albert; Schwab, Daniela; Schienle, Anne
2018-04-23
In western cultures, we are surrounded by appealing visual food cues that stimulate our desire to eat, overeating and subsequent weight gain. Cognitive control of appetite (reappraisal) requires substantial attentional resources and effort in order to work. Therefore, we tested an alternative approach for appetite regulation via functional magnetic resonance imaging. Healthy, normal-weight women were presented with images depicting food (high-/low-caloric), once in combination with a bitter aftertaste (a gustatory stop signal) and once with a neutral taste (water), in a retest design. The aversive aftertaste elicited increased activation in the orbitofrontal/dorsolateral prefrontal cortex (OFC, DLPFC), striatum and frontal operculum during the viewing of high-caloric food (vs. low-caloric food). In addition, the increase in DLPFC activity to high-caloric food in the bitter condition was correlated with reported appetite reduction. The findings indicate that this aftertaste procedure was able to reduce the appetitive value of visual food cues. Copyright © 2018 Elsevier B.V. All rights reserved.
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Reassessment of area postrema's role in motion sickness and conditioned taste aversion
NASA Technical Reports Server (NTRS)
Daunton, Nancy G.; Brizzee, Kenneth R.; Corcoran, Meryl Lee; Crampton, G. H.; Damelio, F.; Elfar, S.; Fox, Robert A.
1991-01-01
On the basis of classical studies on the role of the area psotrema (AP) in motion-induced emesis it was generally accepted that the AP is an essential structure for the production of vomiting in response to motion. However, in more recent studies it has been demonstrated that vomiting induced by motion can still occur in animals in which the AP has been destroyed bilaterally. It was inferred from some of these more recent studies that the AP plays no role in motion-induced emesis. From the standpoint of the current understanding of central nervous system (CNS) plasticity, redundancy, remodeling, unmasking, regeneration, and recovery of function, however, it is important to realize the limitations of using ablation procedures to determine the functional role of a given neural structure in a highly integrated, adaptable central nervous system (CNS). For example, the results of our recent investigations in cat and squirrel monkey on the role of the AP in emesis and conditioned taste aversion induced by motion indicate that while AP lesions do not prevent motion-induced emesis when animals are tested 30 days or more after surgery, the lesions do change the latency to emesis. Thus, contradictory findings from lesion studies must be evaluated not only in terms of species difference, differences in lesioning techniques and extent of lesions, and in stimulus parameters, but also in terms of duration of the recovery period, during which significant recovery of function may take place. In our judgment, inadequate consideration of the foregoing factors could lead to erroneous inferences about given structure's role in the behavior of the intact, nonablated animal.
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Blednov, Y A; Borghese, C M; McCracken, M L; Benavidez, J M; Geil, C R; Osterndorff-Kahanek, E; Werner, D F; Iyer, S; Swihart, A; Harrison, N L; Homanics, G E; Harris, R A
2011-01-01
GABA type A receptors (GABA(A)-Rs) are potential targets of ethanol. However, there are multiple subtypes of this receptor, and, thus far, individual subunits have not been definitively linked with specific ethanol behavioral actions. Interestingly, though, a chromosomal cluster of four GABA(A)-R subunit genes, including α2 (Gabra2), was associated with human alcoholism (Am J Hum Genet 74:705-714, 2004; Pharmacol Biochem Behav 90:95-104, 2008; J Psychiatr Res 42:184-191, 2008). The goal of our study was to determine the role of receptors containing this subunit in alcohol action. We designed an α2 subunit with serine 270 to histidine and leucine 277 to alanine mutations that was insensitive to potentiation by ethanol yet retained normal GABA sensitivity in a recombinant expression system. Knockin mice containing this mutant subunit were tested in a range of ethanol behavioral tests. These mutant mice did not develop the typical conditioned taste aversion in response to ethanol and showed complete loss of the motor stimulant effects of ethanol. Conversely, they also demonstrated changes in ethanol intake and preference in multiple tests. The knockin mice showed increased ethanol-induced hypnosis but no difference in anxiolytic effects or recovery from acute ethanol-induced motor incoordination. Overall, these studies demonstrate that the effects of ethanol at GABAergic synapses containing the α2 subunit are important for specific behavioral effects of ethanol that may be relevant to the genetic linkage of this subunit with human alcoholism.
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Borghese, C. M.; McCracken, M. L.; Benavidez, J. M.; Geil, C. R.; Osterndorff-Kahanek, E.; Werner, D. F.; Iyer, S.; Swihart, A.; Harrison, N. L.; Homanics, G. E.; Harris, R. A.
2011-01-01
GABA type A receptors (GABAA-Rs) are potential targets of ethanol. However, there are multiple subtypes of this receptor, and, thus far, individual subunits have not been definitively linked with specific ethanol behavioral actions. Interestingly, though, a chromosomal cluster of four GABAA-R subunit genes, including α2 (Gabra2), was associated with human alcoholism (Am J Hum Genet 74:705–714, 2004; Pharmacol Biochem Behav 90:95–104, 2008; J Psychiatr Res 42:184–191, 2008). The goal of our study was to determine the role of receptors containing this subunit in alcohol action. We designed an α2 subunit with serine 270 to histidine and leucine 277 to alanine mutations that was insensitive to potentiation by ethanol yet retained normal GABA sensitivity in a recombinant expression system. Knockin mice containing this mutant subunit were tested in a range of ethanol behavioral tests. These mutant mice did not develop the typical conditioned taste aversion in response to ethanol and showed complete loss of the motor stimulant effects of ethanol. Conversely, they also demonstrated changes in ethanol intake and preference in multiple tests. The knockin mice showed increased ethanol-induced hypnosis but no difference in anxiolytic effects or recovery from acute ethanol-induced motor incoordination. Overall, these studies demonstrate that the effects of ethanol at GABAergic synapses containing the α2 subunit are important for specific behavioral effects of ethanol that may be relevant to the genetic linkage of this subunit with human alcoholism. PMID:20876231
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Gastric bypass reduces fat intake and preference
Bueter, Marco; Theis, Nadine; Werling, Malin; Ashrafian, Hutan; Löwenstein, Christian; Athanasiou, Thanos; Bloom, Stephen R.; Spector, Alan C.; Olbers, Torsten; Lutz, Thomas A.
2011-01-01
Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation. PMID:21734019
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Gastric bypass reduces fat intake and preference.
le Roux, Carel W; Bueter, Marco; Theis, Nadine; Werling, Malin; Ashrafian, Hutan; Löwenstein, Christian; Athanasiou, Thanos; Bloom, Stephen R; Spector, Alan C; Olbers, Torsten; Lutz, Thomas A
2011-10-01
Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation.
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Value generalization in human avoidance learning
Robbins, Trevor W; Seymour, Ben
2018-01-01
Generalization during aversive decision-making allows us to avoid a broad range of potential threats following experience with a limited set of exemplars. However, over-generalization, resulting in excessive and inappropriate avoidance, has been implicated in a variety of psychological disorders. Here, we use reinforcement learning modelling to dissect out different contributions to the generalization of instrumental avoidance in two groups of human volunteers (N = 26, N = 482). We found that generalization of avoidance could be parsed into perceptual and value-based processes, and further, that value-based generalization could be subdivided into that relating to aversive and neutral feedback − with corresponding circuits including primary sensory cortex, anterior insula, amygdala and ventromedial prefrontal cortex. Further, generalization from aversive, but not neutral, feedback was associated with self-reported anxiety and intrusive thoughts. These results reveal a set of distinct mechanisms that mediate generalization in avoidance learning, and show how specific individual differences within them can yield anxiety. PMID:29735014
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Value generalization in human avoidance learning.
Norbury, Agnes; Robbins, Trevor W; Seymour, Ben
2018-05-08
Generalization during aversive decision-making allows us to avoid a broad range of potential threats following experience with a limited set of exemplars. However, over-generalization, resulting in excessive and inappropriate avoidance, has been implicated in a variety of psychological disorders. Here, we use reinforcement learning modelling to dissect out different contributions to the generalization of instrumental avoidance in two groups of human volunteers ( N = 26, N = 482). We found that generalization of avoidance could be parsed into perceptual and value-based processes, and further, that value-based generalization could be subdivided into that relating to aversive and neutral feedback - with corresponding circuits including primary sensory cortex, anterior insula, amygdala and ventromedial prefrontal cortex. Further, generalization from aversive, but not neutral, feedback was associated with self-reported anxiety and intrusive thoughts. These results reveal a set of distinct mechanisms that mediate generalization in avoidance learning, and show how specific individual differences within them can yield anxiety. © 2018, Norbury et al.
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Ezak , Meredith J.; Hong , Elizabeth; Chaparro-Garcia , Angela; Ferkey , Denise M.
2010-01-01
Olfaction and some forms of taste (including bitter) are mediated by G protein-coupled signal transduction pathways. Olfactory and gustatory ligands bind to chemosensory G protein-coupled receptors (GPCRs) in specialized sensory cells to activate intracellular signal transduction cascades. G protein-coupled receptor kinases (GRKs) are negative regulators of signaling that specifically phosphorylate activated GPCRs to terminate signaling. Although loss of GRK function usually results in enhanced cellular signaling, Caenorhabditis elegans lacking GRK-2 function are not hypersensitive to chemosensory stimuli. Instead, grk-2 mutant animals do not chemotax toward attractive olfactory stimuli or avoid aversive tastes and smells. We show here that loss-of-function mutations in the transient receptor potential vanilloid (TRPV) channels OSM-9 and OCR-2 selectively restore grk-2 behavioral avoidance of bitter tastants, revealing modality-specific mechanisms for TRPV channel function in the regulation of C. elegans chemosensation. Additionally, a single amino acid point mutation in OCR-2 that disrupts TRPV channel-mediated gene expression, but does not decrease channel function in chemosensory primary signal transduction, also restores grk-2 bitter taste avoidance. Thus, loss of GRK-2 function may lead to changes in gene expression, via OSM-9/OCR-2, to selectively alter the levels of signaling components that transduce or regulate bitter taste responses. Our results suggest a novel mechanism and multiple modality-specific pathways that sensory cells employ in response to aberrant signal transduction. PMID:20176974
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Kinzeler, Nicole R; Travers, Susan P
2011-09-01
The neural control of feeding involves many neuromodulators, including the endogenous opioids that bind μ-opioid receptors (MORs). Injections of the MOR agonist, Damgo, into limbic and hypothalamic forebrain sites increase intake, particularly of palatable foods. Indeed, forebrain Damgo injections increase sucrose-elicited licking but reduce aversive responding (gaping) to quinine, suggesting that MOR activation may enhance taste palatability. A μ-opioid influence on taste reactivity has not been assessed in the brain stem. However, MORs are present in the first-order taste relay, the rostral nucleus of the solitary tract (rNST), and in the immediately subjacent reticular formation (RF), a region known to be essential for consummatory responses. Thus, to evaluate the consequences of rNST/dorsal RF Damgo in this region, we implanted rats with intraoral cannulas, electromyographic electrodes, and brain cannulas aimed at the ventral border of the rNST. Licking and gaping elicited with sucrose, water, and quinine were assessed before and after intramedullary Damgo and saline infusions. Damgo slowed the rate, increased the amplitude, and decreased the size of fluid-induced lick and gape bouts. In addition, the neutral stimulus water, which typically elicits licks, began to evoke gapes. Thus, the current results demonstrate that μ-opioid activation in the rNST/dorsal RF exerts complex effects on oromotor responding that contrast with forebrain effects and are more indicative of a suppressive, rather than a facilitatory effect on ingestion.
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Peña-Quintana, Luis; Llarena, Marta; Reyes-Suárez, Desiderio; Aldámiz-Echevarria, Luis
2017-01-01
Urea-cycle disorders are a group of rare hereditary metabolic diseases characterized by deficiencies of one of the enzymes and transporters involved in the urea cycle, which is necessary for the removal of nitrogen produced from protein breakdown. These hereditary metabolic diseases are characterized by hyperammonemia and life-threatening hyperammonemic crises. Pharmacological treatment of urea-cycle disorders involves alternative nitrogen-scavenging pathways. Sodium benzoate combines with glycine and phenylacetate/phenylbutyrate with glutamine, forming, respectively, hippuric acid and phenylacetylglutamine, which are eliminated in the urine. Among the ammonia-scavenging drugs, sodium phenylbutyrate is a well-known long-term treatment of urea-cycle disorders. It has been used since 1987 as an investigational new drug, and was approved for marketing in the US in 1996 and the EU in 1999. However, sodium phenylbutyrate has an aversive odor and taste, which may compromise patients' compliance, and many patients have reported difficulty in taking this drug. Sodium phenylbutyrate granules are a new tasteless and odor-free formulation of sodium phenylbutyrate, which is indicated in the treatment of urea-cycle disorders. This recently developed taste-masked formulation of sodium phenylbutyrate granules was designed to overcome the considerable issues that taste has on adherence to therapy. Several studies have reported the clinical experience of patients with urea-cycle disorders treated with this new tasteless formulation of sodium phenylbutyrate. Analysis of the data indicated that this taste-masked formulation of sodium phenylbutyrate granules improved quality of life for urea-cycle disorder patients. Furthermore, a postmarketing report on the use of the product has confirmed the previous observations of improved compliance, efficacy, and safety with this taste-masked formulation of sodium phenylbutyrate.
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Narusuye, Kenji; Kinugawa, Aiko; Nagahama, Tatsumi
2005-11-01
Aplysia kurodai distributed along Japan feeds well on Ulva pertusa but rejects Gelidium amansii with distinctive patterned movements of the jaws and radula. On the ventral side of the cerebral M cluster, four cell bodies of higher order neurons that send axons to the buccal ganglia are distributed (CBM neurons). We have previously shown that the dopaminergic CBM1 modulates basic feeding circuits in the buccal ganglia for rejection by firing at higher frequency after application of the aversive taste of seaweed such as Gelidium amansii. In the present experiments immunohistochemical techniques showed that the CBM3 exhibited gamma-aminobutyric acid (GABA)-like immunoreactivity. The CBM3 may be equivalent to the CBI-3 involved in changing the motor programs from rejection to ingestion in Aplysia californica. The responses of the CBM3 to taste stimulation of the lips with seaweed extracts were investigated by the use of calcium imaging. The calcium-sensitive dye, Calcium Green-1, was iontophoretically introduced into a cell body of the CBM3 using a microelectrode. Application of Ulva pertusa or Gelidium amansii extract induced different changes in fluorescence in the CBM3 cell body, indicating that taste of Ulva pertusa initially induced longer-lasting continuous spike responses at slightly higher frequency compared with that of Gelidium amansii. Considering a role of the CBM3 in the pattern selection, these results suggest that elongation of the initial firing response may be a major factor for the CBM3 to switch the buccal motor programs from rejection to ingestion after application of different tastes of seaweeds in Aplysia kurodai. (c) 2005 Wiley Periodicals, Inc.
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Schroer, Adam B; Gross, Joshua D; Kaski, Shane W; Wix, Kim; Siderovski, David P; Vandenbeuch, Aurelie; Setola, Vincent
2018-05-23
The mammalian tastes of sweet, umami, and bitter are initiated by activation of G protein-coupled receptors (GPCRs) of the T1R and T2R families on taste receptor cells. GPCRs signal via nucleotide exchange and hydrolysis, the latter hastened by GTPase-accelerating proteins (GAPs) that include the Regulators of G protein Signaling (RGS) protein family. We previously reported that RGS21, uniquely expressed in Type II taste receptor cells, decreases the potency of bitter-stimulated T2R signaling in cultured cells, consistent with its in vitro GAP activity. However, the role of RGS21 in organismal responses to GPCR-mediated tastants was not established. Here, we characterized mice lacking the Rgs21 fifth exon. Eliminating Rgs21 expression had no effect on body mass accumulation (a measure of alimentation), fungiform papillae number and morphology, circumvallate papillae morphology, and taste bud number. Two-bottle preference tests, however, revealed that Rgs21-null mice have blunted aversion to quinine and denatonium, and blunted preference for monosodium glutamate, the sweeteners sucrose and SC45647, and (surprisingly) NaCl. Observed reductions in GPCR-mediated tastant responses upon Rgs21 loss are opposite to original expectations, given that loss of RGS21-a GPCR signaling negative regulator-should lead to increased responsiveness to tastant-mediated GPCR signaling (all else being equal). Yet, reduced organismal tastant responses are consistent with observations of reduced chorda tympani nerve recordings in Rgs21-null mice. Reduced tastant-mediated responses and behaviors exhibited by adult mice lacking Rgs21 expression since birth have thus revealed an underappreciated requirement for a GPCR GAP to establish the full character of tastant signaling.
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Peña-Quintana, Luis; Llarena, Marta; Reyes-Suárez, Desiderio; Aldámiz-Echevarria, Luis
2017-01-01
Urea-cycle disorders are a group of rare hereditary metabolic diseases characterized by deficiencies of one of the enzymes and transporters involved in the urea cycle, which is necessary for the removal of nitrogen produced from protein breakdown. These hereditary metabolic diseases are characterized by hyperammonemia and life-threatening hyperammonemic crises. Pharmacological treatment of urea-cycle disorders involves alternative nitrogen-scavenging pathways. Sodium benzoate combines with glycine and phenylacetate/phenylbutyrate with glutamine, forming, respectively, hippuric acid and phenylacetylglutamine, which are eliminated in the urine. Among the ammonia-scavenging drugs, sodium phenylbutyrate is a well-known long-term treatment of urea-cycle disorders. It has been used since 1987 as an investigational new drug, and was approved for marketing in the US in 1996 and the EU in 1999. However, sodium phenylbutyrate has an aversive odor and taste, which may compromise patients’ compliance, and many patients have reported difficulty in taking this drug. Sodium phenylbutyrate granules are a new tasteless and odor-free formulation of sodium phenylbutyrate, which is indicated in the treatment of urea-cycle disorders. This recently developed taste-masked formulation of sodium phenylbutyrate granules was designed to overcome the considerable issues that taste has on adherence to therapy. Several studies have reported the clinical experience of patients with urea-cycle disorders treated with this new tasteless formulation of sodium phenylbutyrate. Analysis of the data indicated that this taste-masked formulation of sodium phenylbutyrate granules improved quality of life for urea-cycle disorder patients. Furthermore, a postmarketing report on the use of the product has confirmed the previous observations of improved compliance, efficacy, and safety with this taste-masked formulation of sodium phenylbutyrate. PMID:28919721
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Ahmad, Tasha; Lauzon, Nicole M; de Jaeger, Xavier; Laviolette, Steven R
2013-09-25
Cannabinoid, dopamine (DA), and opiate receptor pathways play integrative roles in emotional learning, associative memory, and sensory perception. Modulation of cannabinoid CB1 receptor transmission within the medial prefrontal cortex (mPFC) regulates the emotional valence of both rewarding and aversive experiences. Furthermore, CB1 receptor substrates functionally interact with opiate-related motivational processing circuits, particularly in the context of reward-related learning and memory. Considerable evidence demonstrates functional interactions between CB1 and DA signaling pathways during the processing of motivationally salient information. However, the role of mPFC CB1 receptor transmission in the modulation of behavioral opiate-reward processing is not currently known. Using an unbiased conditioned place preference paradigm with rats, we examined the role of intra-mPFC CB1 transmission during opiate reward learning. We report that activation or inhibition of CB1 transmission within the prelimbic cortical (PLC) division of the mPFC bidirectionally regulates the motivational valence of opiates; whereas CB1 activation switched morphine reward signaling into an aversive stimulus, blockade of CB1 transmission potentiated the rewarding properties of normally sub-reward threshold conditioning doses of morphine. Both of these effects were dependent upon DA transmission as systemic blockade of DAergic transmission prevented CB1-dependent modulation of morphine reward and aversion behaviors. We further report that CB1-mediated intra-PLC opiate motivational signaling is mediated through a μ-opiate receptor-dependent reward pathway, or a κ-opiate receptor-dependent aversion pathway, directly within the ventral tegmental area. Our results provide evidence for a novel CB1-mediated motivational valence switching mechanism within the PLC, controlling dissociable subcortical reward and aversion pathways.
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Tasting Wine: A Learning Experience
ERIC Educational Resources Information Center
King, Tanya J.; Donaldson, Jilleen A.; Harry, Emma
2012-01-01
This paper describes a field trip by senior undergraduate anthropology students to a local winery, where they participated in a wine-tasting class with winery staff. In response to explicit hints from a wine-tasting facilitator, and more subtle cues from the cultural capital embedded in their surroundings and the winery staff, the students…
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Benoit, S C; Morell, J R; Davidson, T L
1999-12-01
T. L. Davidson, A. M. Altizer, S. C. Benoit, E. K. Walls, and T. L. Powley (1997) reported that rats show facilitated responding to conditioned stimuli (CSs) that predict oil, after administration of the lipoprivic agent, Na-2-mercaptoacetate (MA). This facilitation was blocked by vagal deafferentation. The present article extends that investigation to another structure, the amygdala central nucleus (CN). The CN receives inputs from dorsal vagal nuclei, and neurotoxic lesions of this nucleus are reported to abolish feeding in response to lipoprivic challenges. In Experiment 1, rats with ibotenic acid (IBO) lesions of the CN failed to show enhanced appetitive responding during oil-predicting CSs after administration of MA. Experiment 2 used a conditioned taste-aversion procedure to establish that rats with IBO lesions of the CN were able to discriminate the tastes of sucrose and peanut oil and had intact CS-US representations. It is concluded that the amygdala CN is a necessary structure for the detection of lipoprivic challenges.
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Hilliard, Massimo A; Bergamasco, Carmela; Arbucci, Salvatore; Plasterk, Ronald HA; Bazzicalupo, Paolo
2004-01-01
An animal's ability to detect and avoid toxic compounds in the environment is crucial for survival. We show that the nematode Caenorhabditis elegans avoids many water-soluble substances that are toxic and that taste bitter to humans. We have used laser ablation and a genetic cell rescue strategy to identify sensory neurons involved in the avoidance of the bitter substance quinine, and found that ASH, a polymodal nociceptive neuron that senses many aversive stimuli, is the principal player in this response. Two G protein α subunits GPA-3 and ODR-3, expressed in ASH and in different, nonoverlapping sets of sensory neurons, are necessary for the response to quinine, although the effect of odr-3 can only be appreciated in the absence of gpa-3. We identified and cloned a new gene, qui-1, necessary for quinine and SDS avoidance. qui-1 codes for a novel protein with WD-40 domains and which is expressed in the avoidance sensory neurons ASH and ADL. PMID:14988722
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Aversive Learning of Colored Lights in Walking Honeybees
Kirkerud, Nicholas H.; Schlegel, Ulrike; Giovanni Galizia, C.
2017-01-01
The honeybee has been established as an important model organism in studies on visual learning. So far the emphasis has been on appetitive conditioning, simulating floral discrimination, and homing behavior, where bees perform exceptionally well in visual discrimination tasks. However, bees in the wild also face dangers, and recent findings suggest that what is learned about visual percepts is highly context dependent. A stimulus that follows an unpleasant period, is associated with the feeling of relief- or safety in humans and animals, thus acquiring a positive meaning. Whether this is also the case in honeybees is still an open question. Here, we conditioned bees aversively in a walking arena where each half was illuminated by light of a specific wavelength and intensity, one of which was combined with electric shocks. In this paradigm, the bees' preferences to the different lights were modified through nine conditioning trials, forming robust escape, and avoidance behaviors. Strikingly, we found that while 465 nm (human blue) and 590 nm (human yellow) lights both could acquire negative valences (inducing avoidance response), 525 nm (human green) light could not. This indicates that green light holds an innate meaning of safety which is difficult to overrule even through intensive aversive conditioning. The bees had slight initial preferences to green over the blue and the yellow lights, which could be compensated by adjusting light intensity. However, this initial bias played a minor role while the chromatic properties were the most salient characteristics of the light stimuli during aversive conditioning. Moreover, bees could learn the light signaling safety, revealing the existence of a relief component in aversive operant conditioning, similar to what has been observed in other animals. PMID:28588460
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Miskovic, Vladimir; Keil, Andreas
2015-01-01
The visual system is biased towards sensory cues that have been associated with danger or harm through temporal co-occurrence. An outstanding question about conditioning-induced changes in visuocortical processing is the extent to which they are driven primarily by top-down factors such as expectancy or by low-level factors such as the temporal proximity between conditioned stimuli and aversive outcomes. Here, we examined this question using two different differential aversive conditioning experiments: participants learned to associate a particular grating stimulus with an aversive noise that was presented either in close temporal proximity (delay conditioning experiment) or after a prolonged stimulus-free interval (trace conditioning experiment). In both experiments we probed cue-related cortical responses by recording steady-state visual evoked potentials (ssVEPs). Although behavioral ratings indicated that all participants successfully learned to discriminate between the grating patterns that predicted the presence versus absence of the aversive noise, selective amplification of population-level responses in visual cortex for the conditioned danger signal was observed only when the grating and the noise were temporally contiguous. Our findings are in line with notions purporting that changes in the electrocortical response of visual neurons induced by aversive conditioning are a product of Hebbian associations among sensory cell assemblies rather than being driven entirely by expectancy-based, declarative processes. PMID:23398582
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NASA Astrophysics Data System (ADS)
Rabin, B.; Joseph, J.; Shukitt-Hale, B.
Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation- induced disruption of dopaminergic function disrupts a variety of behaviors that are dependent upon the integrity of the dopaminergic system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, spatial learning and memory (Morris water maze), and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current presentation will review the data relevant to the degree to which these characteristics are in fact common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. Supported by N.A.S.A. Grant NAG9-1190.
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Aversive olfactory associative memory loses odor specificity over time
König, Christian; Antwi-Adjei, Emmanuel; Ganesan, Mathangi; Kilonzo, Kasyoka; Viswanathan, Vignesh; Durairaja, Archana; Voigt, Anne
2017-01-01
ABSTRACT Avoiding associatively learned predictors of danger is crucial for survival. Aversive memories can, however, become counter-adaptive when they are overly generalized to harmless cues and contexts. In a fruit fly odor–electric shock associative memory paradigm, we found that learned avoidance lost its specificity for the trained odor and became general to novel odors within a day of training. We discuss the possible neural circuit mechanisms of this effect and highlight the parallelism to over-generalization of learned fear behavior after an incubation period in rodents and humans, with due relevance for post-traumatic stress disorder. PMID:28468811
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Lei, Kelly; Wegner, Scott A.; Yu, Ji-Hwan; Simms, Jeffrey A.; Hopf, F. Woodward
2016-01-01
Addiction is mediated in large part by pathological motivation for rewarding, addictive substances, and alcohol-use disorders (AUDs) continue to extract a very high physical and economic toll on society. Compulsive alcohol drinking, where intake continues despite negative consequences, is considered a particular obstacle during treatment of AUDs. Aversion-resistant drives for alcohol have been modeled in rodents, where animals continue to consume even when alcohol is adulterated with the bitter tastant quinine, or is paired with another aversive consequence. Here, we describe a two-bottle choice paradigm where C57BL/6 mice first had 24-h access to 15% alcohol or water. Afterward, they drank quinine-free alcohol (alcohol-only) or alcohol with quinine (100 μM), in a limited daily access (LDA) two-bottle-choice paradigm (2 h/day, 5 days/week, starting 3 h into the dark cycle), and achieved nearly binge-level blood alcohol concentrations. Interestingly, a single, initial 24-h experience with alcohol-only enhanced subsequent quinine-resistant drinking. In contrast, mice that drank alcohol–quinine in the 24-h session showed significantly reduced alcohol–quinine intake and preference during the subsequent LDA sessions, relative to mice that drank alcohol-only in the initial 24-h session and alcohol–quinine in LDA sessions. Thus, mice could find the concentration of quinine we used aversive, but were able to disregard the quinine after a single alcohol-only drinking session. Finally, mice had low intake and preference for quinine in water, both before and after weeks of alcohol-drinking sessions, suggesting that quinine resistance was not a consequence of increased quinine preference after weeks of drinking of alcohol–quinine. Together, we demonstrate that a single alcohol-only session was sufficient to enable subsequent aversion-resistant consumption in C57BL/6 mice, which did not reflect changes in quinine taste palatability. Given the rapid development of quinine-resistant alcohol drinking patterns, this model provides a simple, quick, and robust method for uncovering the mechanisms that promote aversion-resistant consumption. PMID:27788780
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Lei, Kelly; Wegner, Scott A; Yu, Ji-Hwan; Simms, Jeffrey A; Hopf, F Woodward
2016-09-01
Addiction is mediated in large part by pathological motivation for rewarding, addictive substances, and alcohol-use disorders (AUDs) continue to extract a very high physical and economic toll on society. Compulsive alcohol drinking, where intake continues despite negative consequences, is considered a particular obstacle during treatment of AUDs. Aversion-resistant drives for alcohol have been modeled in rodents, where animals continue to consume even when alcohol is adulterated with the bitter tastant quinine, or is paired with another aversive consequence. Here, we describe a two-bottle choice paradigm where C57BL/6 mice first had 24-h access to 15% alcohol or water. Afterward, they drank quinine-free alcohol (alcohol-only) or alcohol with quinine (100 μM), in a limited daily access (LDA) two-bottle-choice paradigm (2 h/day, 5 days/week, starting 3 h into the dark cycle), and achieved nearly binge-level blood alcohol concentrations. Interestingly, a single, initial 24-h experience with alcohol-only enhanced subsequent quinine-resistant drinking. In contrast, mice that drank alcohol-quinine in the 24-h session showed significantly reduced alcohol-quinine intake and preference during the subsequent LDA sessions, relative to mice that drank alcohol-only in the initial 24-h session and alcohol-quinine in LDA sessions. Thus, mice could find the concentration of quinine we used aversive, but were able to disregard the quinine after a single alcohol-only drinking session. Finally, mice had low intake and preference for quinine in water, both before and after weeks of alcohol-drinking sessions, suggesting that quinine resistance was not a consequence of increased quinine preference after weeks of drinking of alcohol-quinine. Together, we demonstrate that a single alcohol-only session was sufficient to enable subsequent aversion-resistant consumption in C57BL/6 mice, which did not reflect changes in quinine taste palatability. Given the rapid development of quinine-resistant alcohol drinking patterns, this model provides a simple, quick, and robust method for uncovering the mechanisms that promote aversion-resistant consumption. Copyright © 2016 Elsevier Inc. All rights reserved.
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Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat.
Greenwood, Michael P; Greenwood, Mingkwan; Paton, Julian F R; Murphy, David
2014-01-01
Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions.
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Salt Appetite Is Reduced by a Single Experience of Drinking Hypertonic Saline in the Adult Rat
Greenwood, Michael P.; Greenwood, Mingkwan; Paton, Julian F. R.; Murphy, David
2014-01-01
Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786
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USDA-ARS?s Scientific Manuscript database
Studies were conducted to address conditioned flavour aversion (CFA) and place avoidance learning in hamsters given injections of alkaloid extracts from tall larkspur (Delphinium barbeyi), to determine if larkspur had reinforcing or negative properties sufficient to cause place avoidance or preferen...
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Osorio-Gómez, Daniel; Guzmán-Ramos, Kioko
2017-01-01
The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the gustatory zone of the IC during CTA retrieval. Additionally, it has been reported that the amygdala–IC interaction is highly involved in CTA memory establishment. Therefore, we evaluated the effects of infusions of an AMPA receptor antagonist (CNQX) and a NMDA receptor antagonist (APV) into the amygdala on CTA retrieval and IC neurotransmitter levels. Infusion of APV into the amygdala impaired glutamate augmentation within the IC, whereas dopamine and norepinephrine levels augmentation persisted and a reliable CTA expression was observed. Conversely, CNQX infusion into the amygdala impaired the aversion response, as well as norepinephrine and dopamine augmentations in the IC. Interestingly, CNQX infusion did not affect glutamate elevation in the IC. To evaluate the functional meaning of neurotransmitters elevations within the IC on CTA response, we infused specific antagonists for the AMPA, NMDA, D1, and β-adrenergic receptor before retrieval. Results showed that activation of AMPA, D1, and β-adrenergic receptors is necessary for CTA expression, whereas NMDA receptors are not involved in the aversion response. PMID:27980072
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1989-01-01
Contents include: effects of ethiofos (WR-2721) and radiation on monkey visual discrimination performance; gamma radiolysis of RNA: an ESR and spin-trapping study; phospholipid storage in the secretory granule of the mast cell; physiological localization of an agonist-sensitive pool of Ca{sup 2+} in parotid acinar cells; changes in canine neutrophil function(s) following cellular isolation by percoll gradient centrifugation or isotoniclysis; impaired repair of uvc-induced DNA damage in l5178Y-R cells: sedimentation studies with the use of 5'-bromodeoxyuridine photolysis; comparative behavioral toxicity of four sulfhydryl radioprotective compounds in mice: WR-2721, cysteamine, diethyldithiocarbamate, and n-acetylcysteine; measurement of the radiosensitivity of rat marrow by flowmore » cytometry; radioprotection by biological response modifiers alone and in combination with WR-2721; postirradiation glucan administration enhances the radioprotective effects of WR-2721; attenuation and cross-attenuation in taste aversion learning in the rat: studies with ionizing radiation, lithium chloride, and ethanol; a low-energy x-ray irradiator for electrophysiological studies; thermospray liquid chromatography mass spectrometry of thiol radioprotective agents: characteristic spectra; radioprotection by leukotrienes: is there a receptor mechanism and a low-energy x-ray irradiator for electrophysiological studies.« less
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Brain–immune interactions and the neural basis of disease-avoidant ingestive behaviour
Pacheco-López, Gustavo; Bermúdez-Rattoni, Federico
2011-01-01
Neuro–immune interactions are widely manifested in animal physiology. Since immunity competes for energy with other physiological functions, it is subject to a circadian trade-off between other energy-demanding processes, such as neural activity, locomotion and thermoregulation. When immunity is challenged, this trade-off is tilted to an adaptive energy protecting and reallocation strategy that is identified as ‘sickness behaviour’. We review diverse disease-avoidant behaviours in the context of ingestion, indicating that several adaptive advantages have been acquired by animals (including humans) during phylogenetic evolution and by ontogenetic experiences: (i) preventing waste of energy by reducing appetite and consequently foraging/hunting (illness anorexia), (ii) avoiding unnecessary danger by promoting safe environments (preventing disease encounter by olfactory cues and illness potentiation neophobia), (iii) help fighting against pathogenic threats (hyperthermia/somnolence), and (iv) by associative learning evading specific foods or environments signalling danger (conditioned taste avoidance/aversion) and/or at the same time preparing the body to counteract by anticipatory immune responses (conditioning immunomodulation). The neurobiology behind disease-avoidant ingestive behaviours is reviewed with special emphasis on the body energy balance (intake versus expenditure) and an evolutionary psychology perspective. PMID:22042916
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Leaves of Hippophae rhamnoides prevent taste aversion in gamma-irradiated rats.
Gupta, Vanita; Bala, Madhu; Prasad, Jagdish; Singh, Surinder; Gupta, Manish
2011-12-01
Hippophae rhamnoides (Sea buckthorn), a traditionally known plant for nutritional and therapeutic values, is under active investigation for radioprotective properties. This study investigated effects of aqueous leaf extract from H. rhamnoides on (60)Co-γ-radiation induced changes in behavior, oxidative stress and serotonin levels in jejunum and plasma of rats. Conditioned taste aversion (CTA) was chosen as the assay to record behavioral changes and was assessed in terms of saccharine preference ratio (SPR). Whole body (60)Co-γ-irradiation (2 Gy) induced significant nonrecoverable CTA (25.6 ± 3.6% SPR, t(6) = 3.499, p < .05) and loss in body weight (b.w.). One time treatment with leaf extract before irradiation, countered radiation induced CTA and loss in body weight. The 12 mg/kg b.w. concentration of leaf extract caused complete extinction of CTA [100.3 ± 6.4% SPR, t(6) = 5.879, p < .01] after day 3 and the effect was significantly higher than positive control, Ondansetrone (70.0 ± 8.9% SPR). Treatment with leaf extract before irradiation significantly countered radiation induced (1) decrease in antioxidant protection, (2) increase in levels of corticosterone (CS) in plasma, (3) increase in levels of serotonin in jejunum and plasma. Present investigation demonstrated that H. rhamnoides leaf extract prevented behavioral changes induced at clinical radiation doses. Hippophae leaves are nontoxic and are being consumed as tea and other beverages. CTA in rats is a considered parallel process to nausea and vomiting in human beings. These findings, put together, suggest that dietary supplements from Hippophae leaves could be developed for preventing behavioral changes in subjects exposed to radiation.
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Klockars, Oscar A; Klockars, Anica; Levine, Allen S; Olszewski, Pawel K
2018-04-11
Oxytocin (OT) at acting central nuclei decreases meal size and reduces intake of palatable sweet solutions. It remains largely unclear as to which brain sites mediate OT's effect on palatability versus energy or the combination of those aspects of consumption. Here, we expanded the search for sites that mediate anorexigenic properties of OT by focusing on two subdivisions of the amygdala, its central (CNA) and basolateral (BLA) nuclei. We injected OT directly into the BLA or CNA in rats and assessed intake of standard chow induced by energy deprivation and intake of sweet solutions in nondeprived animals. We examined whether these effects are reversible by OT receptor (OTr) antagonism and whether OT presence in BLA or CNA induces taste aversion. We also determined the effect of energy deprivation and exposure to sweet saccharin on BLA and CNA expression of OTr mRNA. OT administration in BLA at 0.3 μg and in CNA at 1 μg reduced standard chow intake after deprivation by ~25%. Only administration of OT in BLA was effective in suppressing consumption of sucrose and saccharin solutions. The anorexigenic effects of OT in BLA and CNA were attenuated by OTr antagonist, L-368,899, pretreatment. OT at anorexigenic doses did not promote acquisition of taste aversion. BLA OTr mRNA expression was affected by exposure to palatable saccharin, whereas that of CNA OTr, by energy deprivation. OT in the amygdala moderately decreases food intake. The functional relationship between amygdalar OT and energy intake versus palatability-driven intake depends on the discrete localization of the OTr within this complex structure.
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Kim, Kyu-Nam; Kim, Bom-Taeck; Kim, Young-Sang; Lee, Jong-Ho; Jahng, Jeong Won
2014-05-05
Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose-lithium pairing, and then received dexamethasone or vehicle at 30min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX+B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA. Copyright © 2014 Elsevier B.V. All rights reserved.
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Dietary fibers reduce food intake by satiation without conditioned taste aversion in mice.
Rasoamanana, Rojo; Even, Patrick C; Darcel, Nicolas; Tomé, Daniel; Fromentin, Gilles
2013-02-17
It is well known that intake of dietary fiber (DF) potently decreases food intake and feelings of hunger and/or promotes satiety ratings. However, the mechanisms explaining these effects are not well characterized. This work was performed to determine which of satiation and/or satiety mechanisms provoke the decrease of food intake induced by DF in mice. We tested in an intra-group protocol a low-viscosity (LV, fructo-oligosaccharide), a viscous (VP, guar gum) and a high-viscosity (HV, mixture of guar gum and fructo-oligosaccharide) preload. These were given to mice by intra-gastric gavage. It appeared that viscous preloads such as VP and HV reduced the daily energy intake by 14% and 21% respectively. The strong effect of HV was mainly due to a large decrease of meal size (by 57%) and meal duration (by 65%) with no effect on ingestion rate during the first 30 min after administration. Therefore, the DF-induced decrease of energy intake was due to a satiation mechanism. This is further supported by a 3-fold increased sensitization of neurons in the nucleus of the solitary tract as observed by c-Fos protein immunolabelling. No compensation of food intake was observed during the rest of the day, a phenomenon that may be explained by the fact that metabolic rate remained high despite the lower food intake. We have also shown that the DF-induced inhibition of food intake was not paired with a conditioned taste aversion. To conclude, this work demonstrates that DF inhibits food intake by increasing satiation during ~1h after administration. Copyright © 2012 Elsevier Inc. All rights reserved.
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ERIC Educational Resources Information Center
Capuano, Carolyn
1977-01-01
Describes taste experiences that are used to spark interest in studying high school biology. Emphasizes learning about survival, poisonous plants, endangered species, economic and nutritional importance of various organisms, and cultural education. (CS)
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[The sense of taste in a clinical setting].
Fjaeldstad, Alexander; Fernandes, Henrique; Nyengaard, Jens Randel; Ovesen, Therese
2018-04-30
As a gatekeeper, taste buds forage chemicals to identify both nutrition and toxins. This can be the decisive difference between initiating the swallow reflex or spitting out the oral contents. In addition to this simple function the sense of taste takes part in more complex relations such as reflexes vs learning, perception vs expectation, and pleasure vs disgust. All relations, which can be perturbed into unbalance, create great discomfort in patients suffering from a dysfunctional sense of taste. This review discusses the most important mechanisms of taste function and dysfunction as well as the possible avenues for treatment of the disorders.
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Cross-modal Associations between Real Tastes and Colors.
Saluja, Supreet; Stevenson, Richard J
2018-06-02
People make reliable and consistent matches between taste and color. However, in contrast to other cross-modal correspondences, all of the research to date has used only taste words (and often color words too), potentially limiting our understanding of how taste-color matches arise. Here, participants sampled the five basic tastes, at three concentration steps, and selected their best matching color from a color-wheel. This test was repeated, and in addition, participants evaluated the valence of the taste and their color choice, as well as the qualities/intensities of the taste stimuli. Participants were then presented with taste names and asked to generate the best matching color name, as well as reporting how they made their earlier choices. Color selections were reliable and consistent, and closely followed those based on taste word matches obtained in this and prior studies. Most participants reported basing their color choices on their associated taste-object (often foods). There was marked similarity in valence between taste and color choices, and the saturation of color choices was related to tastant concentration. We discuss what drives color-taste pairings, with learning suggested as one possible mechanism.
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Daisley, Jonathan N.; Gruss, Michael; Rose, Steven P. R.; Braun, Katharina
1998-01-01
In the young chick, the intermediate medial hyperstriatum ventrale is involved in learning paradigms, including imprinting and passive avoidance learning. Biochemical changes in the intermediate medial hyperstriatum ventrale following learning include an up-regulation of amino-acid transmitter levels and receptor activity. To follow the changes of extracellular amino acid levels during passive avoidance training, we used an in vivo microdialysis technique. Probes were implanted in chicks before training the animals, either on a methyl- anthranylate-or water-coated bead. One hour later, recall was tested in both groups by presenting a similar bead. An increase of extra-cellular glutamate levels accompanied training and testing in both groups; during training, glutamate release was higher in methylanthranylate- trained than in water-trained chicks. When compared with the methylanthranylate-trained chicks during testing, the water-trained chicks showed enhanced extra-cellular glutamate levels. No other amino acid examined showed significant changes. After testing, the chicks were anesthetized and release- stimulated with an infusion of 50 mM potassium. Extra-cellular glutamate and taurine levels were significantly increased in both methylanthranylate-and water-trained chicks. The presentation of methylanthranylate as an. olfactory stimulus significantly enhanced glutamate levels, especially in methylanthranylate-trained chicks. The results suggest that such changes in extra-cellular glutamate levels in the intermediate medial hyperstriatum ventrale accompany pecking at either the water- or the methylanthranylate-bead. The taste of the aversant may be responsible for the greater increases found in methylanthranylate-trained birds. PMID:9920682
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Midbrain dopamine neurons signal aversion in a reward-context-dependent manner
Matsumoto, Hideyuki; Tian, Ju; Uchida, Naoshige; Watabe-Uchida, Mitsuko
2016-01-01
Dopamine is thought to regulate learning from appetitive and aversive events. Here we examined how optogenetically-identified dopamine neurons in the lateral ventral tegmental area of mice respond to aversive events in different conditions. In low reward contexts, most dopamine neurons were exclusively inhibited by aversive events, and expectation reduced dopamine neurons’ responses to reward and punishment. When a single odor predicted both reward and punishment, dopamine neurons’ responses to that odor reflected the integrated value of both outcomes. Thus, in low reward contexts, dopamine neurons signal value prediction errors (VPEs) integrating information about both reward and aversion in a common currency. In contrast, in high reward contexts, dopamine neurons acquired a short-latency excitation to aversive events that masked their VPE signaling. Our results demonstrate the importance of considering the contexts to examine the representation in dopamine neurons and uncover different modes of dopamine signaling, each of which may be adaptive for different environments. DOI: http://dx.doi.org/10.7554/eLife.17328.001 PMID:27760002
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Differences in Risk Aversion between Young and Older Adults.
Albert, Steven M; Duffy, John
2012-01-15
Research on decision-making strategies among younger and older adults suggests that older adults may be more risk averse than younger people in the case of potential losses. These results mostly come from experimental studies involving gambling paradigms. Since these paradigms involve substantial demands on memory and learning, differences in risk aversion or other features of decision-making attributed to age may in fact reflect age-related declines in cognitive abilities. In the current study, older and younger adults completed a simpler, paired lottery choice task used in the experimental economics literature to elicit risk aversion. A similar approach was used to elicit participants' discount rates. The older adult group was more risk averse than younger adults (p < .05) and also had a higher discount rate (15.6-21.0% vs. 10.3-15.5%, p < .01), indicating lower expected utility from future income. Risk aversion and implied discount rates were weakly correlated. It may be valuable to investigate developmental changes in neural correlates of decision-making across the lifespan.
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Differences in Risk Aversion between Young and Older Adults
Albert, Steven M.; Duffy, John
2013-01-01
Research on decision-making strategies among younger and older adults suggests that older adults may be more risk averse than younger people in the case of potential losses. These results mostly come from experimental studies involving gambling paradigms. Since these paradigms involve substantial demands on memory and learning, differences in risk aversion or other features of decision-making attributed to age may in fact reflect age-related declines in cognitive abilities. In the current study, older and younger adults completed a simpler, paired lottery choice task used in the experimental economics literature to elicit risk aversion. A similar approach was used to elicit participants' discount rates. The older adult group was more risk averse than younger adults (p < .05) and also had a higher discount rate (15.6-21.0% vs. 10.3-15.5%, p < .01), indicating lower expected utility from future income. Risk aversion and implied discount rates were weakly correlated. It may be valuable to investigate developmental changes in neural correlates of decision-making across the lifespan. PMID:24319671
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Sublethal landrin toxicity: Behavioral and physiological effects on captive vultures
Forthman-Quick, D.L.; Hill, E.F.
1988-01-01
Use of conditioned taste aversion (CTA) has been proposed to reduce consumption of California condor (Gymnogyps californianus) eggs by ravens (Corvus corax). Although landrin has induced aversions in ravens and other birds, no data were available on behavioral and physiological effects of landrin on condors, non-target birds that might consume treated eggs. Because condors are endangered, we selected taxonomically related surrogates to approximate the effects on condors of acute oral doses of landrin. Seven black vultures (Coragyps atratus), 2 turkey vultures (Cathartes aura), and 2 king vultures (Sarcoramphus papa) received landrin and placebo treatments 1 week apart. Plasma cholinesterase (ChE) activity was monitored at zero, 3, and 24 hours posttreatment, and behavioral observations were made for 2 hours posttreatment. The doses tested were nonlethal, and ChE levels approached normal within 24 hours after treatment. Only the frequency of vomiting differed statistically between the placebo and landrin treatment. We conclude that with appropriate precautions, landrin can be used in applications of CTA to discourage consumption of condor eggs by ravens, while posing no apparent risk to reintroduced condors.
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Disentangling taste and toxicity in aposematic prey
Holen, Øistein Haugsten
2013-01-01
Many predators quickly learn to avoid attacking aposematic prey. If the prey vary in toxicity, the predators may alternatively learn to capture and taste-sample prey carefully before ingesting or rejecting them (go-slow behaviour). An increase in prey toxicity is generally thought to decrease predation on prey populations. However, while prey with a higher toxin load are more harmful to ingest, they may also be easier to recognize and reject owing to greater distastefulness, which can facilitate a taste-sampling foraging strategy. Here, the classic diet model is used to study the separate effects of taste and toxicity on predator preferences. The taste-sampling process is modelled using signal detection theory. The model is applicable to automimicry and Batesian mimicry. It shows that when the defensive toxin is sufficiently distasteful, a mimicry complex may be less profitable to the predator and better protected against predation if the models are moderately toxic than if they are highly toxic. Moreover, taste mimicry can reduce the profitability of the mimicry complex and increase protection against predation. The results are discussed in relation to the selection pressures acting on prey defences and the evolution of mimicry. PMID:23256198
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Disentangling taste and toxicity in aposematic prey.
Holen, Øistein Haugsten
2013-02-22
Many predators quickly learn to avoid attacking aposematic prey. If the prey vary in toxicity, the predators may alternatively learn to capture and taste-sample prey carefully before ingesting or rejecting them (go-slow behaviour). An increase in prey toxicity is generally thought to decrease predation on prey populations. However, while prey with a higher toxin load are more harmful to ingest, they may also be easier to recognize and reject owing to greater distastefulness, which can facilitate a taste-sampling foraging strategy. Here, the classic diet model is used to study the separate effects of taste and toxicity on predator preferences. The taste-sampling process is modelled using signal detection theory. The model is applicable to automimicry and batesian mimicry. It shows that when the defensive toxin is sufficiently distasteful, a mimicry complex may be less profitable to the predator and better protected against predation if the models are moderately toxic than if they are highly toxic. Moreover, taste mimicry can reduce the profitability of the mimicry complex and increase protection against predation. The results are discussed in relation to the selection pressures acting on prey defences and the evolution of mimicry.
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Zarrinkalam, Ebrahim; Heidarianpour, Ali; Salehi, Iraj; Ranjbar, Kamal; Komaki, Alireza
2016-07-15
Continuous morphine consumption contributes to the development of cognitive disorders. This work investigates the impacts of different types of exercise on learning and memory in morphine-dependent rats. Forty morphine-dependent rats were randomly divided into five groups: sedentary-dependent (Sed-D), endurance exercise-dependent (En-D), strength exercise-dependent (St-D), and combined (concurrent) exercise-dependent (Co-D). Healthy rats were used as controls (Con). After 10weeks of regular exercise (endurance, strength, and concurrent; each five days per week), spatial and aversive learning and memory were assessed using the Morris water maze and shuttle box tests. The results showed that morphine addiction contributes to deficits in spatial learning and memory. Furthermore, each form of exercise training restored spatial learning and memory performance in morphine-dependent rats to levels similar to those of healthy controls. Aversive learning and memory during the acquisition phase were not affected by morphine addiction or exercise, but were significantly decreased by morphine dependence. Only concurrent training returned the time spent in the dark compartment in the shuttle box test to control levels. These findings show that different types of exercise exert similar effects on spatial learning and memory, but show distinct effects on aversive learning and memory. Further, morphine dependence-induced deficits in cognitive function were blocked by exercise. Therefore, different exercise regimens may represent practical treatment methods for cognitive and behavioral impairments associated with morphine-related disease. Copyright © 2016 Elsevier Inc. All rights reserved.
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Loss of CaMKI function disrupts salt aversive learning in C. elegans.
Lim, Jana P; Fehlauer, Holger; Das, Alakananda; Saro, Gabriella; Glauser, Dominique A; Brunet, Anne; Goodman, Miriam B
2018-06-06
The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior may help animals avoid areas without food. While some genes have been implicated in this salt aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt aversive learning behavior in C. elegans hermaphrodites. We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of cmk-1 has subtle effects on sensory-evoked calcium responses in ASE axons and their modulation by salt conditioning. Our study implicates the expression of the conserved CaMKI/CMK-1 in chemosensory neurons as a regulator of behavioral plasticity to environmental salt in C. elegans SIGNIFICANCE STATEMENT Like other animals, the nematode Caenorhabditis elegans depends on salt for survival and navigates toward high concentrations of this essential mineral. Besides its role as an essential nutrient, salt also causes osmotic stress at high concentrations. A growing body of evidence indicates that C. elegans balances the requirement for salt with the danger it presents through a process called salt aversive learning. We show that this behavior depends on expression of a calcium/calmodulin-dependent kinase, CMK-1, in the ASE salt sensing neurons. Our study identifies CMK-1 and salt-sensitive chemosensory neurons as key factors in this form of behavioral plasticity. Copyright © 2018 the authors.
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Evolution of social learning when high expected payoffs are associated with high risk of failure.
Arbilly, Michal; Motro, Uzi; Feldman, Marcus W; Lotem, Arnon
2011-11-07
In an environment where the availability of resources sought by a forager varies greatly, individual foraging is likely to be associated with a high risk of failure. Foragers that learn where the best sources of food are located are likely to develop risk aversion, causing them to avoid the patches that are in fact the best; the result is sub-optimal behaviour. Yet, foragers living in a group may not only learn by themselves, but also by observing others. Using evolutionary agent-based computer simulations of a social foraging game, we show that in an environment where the most productive resources occur with the lowest probability, socially acquired information is strongly favoured over individual experience. While social learning is usually regarded as beneficial because it filters out maladaptive behaviours, the advantage of social learning in a risky environment stems from the fact that it allows risk aversion to be circumvented and the best food source to be revisited despite repeated failures. Our results demonstrate that the consequences of individual risk aversion may be better understood within a social context and suggest one possible explanation for the strong preference for social information over individual experience often observed in both humans and animals.
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Evolution of social learning when high expected payoffs are associated with high risk of failure
Arbilly, Michal; Motro, Uzi; Feldman, Marcus W.; Lotem, Arnon
2011-01-01
In an environment where the availability of resources sought by a forager varies greatly, individual foraging is likely to be associated with a high risk of failure. Foragers that learn where the best sources of food are located are likely to develop risk aversion, causing them to avoid the patches that are in fact the best; the result is sub-optimal behaviour. Yet, foragers living in a group may not only learn by themselves, but also by observing others. Using evolutionary agent-based computer simulations of a social foraging game, we show that in an environment where the most productive resources occur with the lowest probability, socially acquired information is strongly favoured over individual experience. While social learning is usually regarded as beneficial because it filters out maladaptive behaviours, the advantage of social learning in a risky environment stems from the fact that it allows risk aversion to be circumvented and the best food source to be revisited despite repeated failures. Our results demonstrate that the consequences of individual risk aversion may be better understood within a social context and suggest one possible explanation for the strong preference for social information over individual experience often observed in both humans and animals. PMID:21508013
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Stability of retrieved memory: inverse correlation with trace dominance.
Eisenberg, Mark; Kobilo, Tali; Berman, Diego E; Dudai, Yadin
2003-08-22
In memory consolidation, the memory trace stabilizes and becomes resistant to certain amnesic agents. The textbook account is that for any memorized item, consolidation starts and ends just once. However, evidence has accumulated that upon activation in retrieval, the trace may reconsolidate. Whereas some authors reported transient renewed susceptibility of retrieved memories to consolidation blockers, others could not detect it. Here, we report that in both conditioned taste aversion in the rat and fear conditioning in the medaka fish, the stability of retrieved memory is inversely correlated with the control of behavior by that memory. This result may explain some conflicting findings on reconsolidation of activated memories.
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Aversive Learning Modulates Cortical Representations of Object Categories
Dunsmoor, Joseph E.; Kragel, Philip A.; Martin, Alex; LaBar, Kevin S.
2014-01-01
Experimental studies of conditioned learning reveal activity changes in the amygdala and unimodal sensory cortex underlying fear acquisition to simple stimuli. However, real-world fears typically involve complex stimuli represented at the category level. A consequence of category-level representations of threat is that aversive experiences with particular category members may lead one to infer that related exemplars likewise pose a threat, despite variations in physical form. Here, we examined the effect of category-level representations of threat on human brain activation using 2 superordinate categories (animals and tools) as conditioned stimuli. Hemodynamic activity in the amygdala and category-selective cortex was modulated by the reinforcement contingency, leading to widespread fear of different exemplars from the reinforced category. Multivariate representational similarity analyses revealed that activity patterns in the amygdala and object-selective cortex were more similar among exemplars from the threat versus safe category. Learning to fear animate objects was additionally characterized by enhanced functional coupling between the amygdala and fusiform gyrus. Finally, hippocampal activity co-varied with object typicality and amygdala activation early during training. These findings provide novel evidence that aversive learning can modulate category-level representations of object concepts, thereby enabling individuals to express fear to a range of related stimuli. PMID:23709642
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Bentz, Dorothée; Michael, Tanja; de Quervain, Dominique J-F; Wilhelm, Frank H
2010-03-01
Current neurophysiological and psychological accounts view exposure therapy as the clinical analog of extinction learning that results in persistent modifications of the fear memory involved in the pathogenesis, symptomatology, and maintenance of anxiety disorders. Evidence from studies in animals and humans indicate that glucocorticoids have the potential to facilitate the processes that underlie extinction learning during exposure therapy. Particularly, glucocorticoids can restrict retrieval of previous aversive learning episodes and enhance consolidation of memory traces relating to non-fearful responding in feared situations. Thus, glucocorticoid treatment especially in combination with exposure therapy might be a promising approach to optimize treatment of anxiety disorders. This review examines the processes involved in aversive conditioning, fear learning and fear extinction, and how glucocorticoids might enhance restructuring of fear memories during therapy. Copyright 2009 Elsevier Ltd. All rights reserved.
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ERIC Educational Resources Information Center
Geddes, Lisa H.; McQuillan, H. James; Aiken, Alastair; Vergoz, Vanina; Mercer, Alison R.
2013-01-01
Here, we examine effects of the steroid hormone, 20-hydroxyecdysone (20-E), on associative olfactory learning in the honeybee, "Apis mellifera." 20-E impaired the bees' ability to associate odors with punishment during aversive conditioning, but did not interfere with their ability to associate odors with a food reward (appetitive…
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Facial affective reactions to bitter-tasting foods and body mass index in adults.
Garcia-Burgos, D; Zamora, M C
2013-12-01
Differences in food consumption among body-weight statuses (e.g., higher fruit intake linked with lower body mass index (BMI) and energy-dense products with higher BMI) has raised the question of why people who are overweight or are at risk of becoming overweight eat differently from thinner people. One explanation, in terms of sensitivity to affective properties of food, suggests that palatability-driven consumption is likely to be an important contributor to food intake, and therefore body weight. Extending this approach to unpalatable tastes, we examined the relationship between aversive reactions to foods and BMI. We hypothesized that people who have a high BMI will show more negative affective reactions to bitter-tasting stimuli, even after controlling for sensory perception differences. Given that hedonic reactions may influence consumption even without conscious feelings of pleasure/displeasure, the facial expressions were included in order to provide more direct access to affective systems than subjective reports. Forty adults (28 females, 12 males) participated voluntarily. Their ages ranged from 18 to 46 years (M=24.2, SD=5.8). On the basis of BMI, participants were classified as low BMI (BMI<20; n=20) and high BMI (BMI>23; n=20). The mean BMI was 19.1 for low BMI (SD=0.7) and 25.2 for high BMI participants (SD=1.8). Each subject tasted 5 mL of a grapefruit juice drink and a bitter chocolate drink. Subjects rated the drinks' hedonic and incentive value, familiarity and bitter intensity immediately after each stimulus presentation. The results indicated that high BMI participants reacted to bitter stimuli showing more profound changes from baseline in neutral and disgust facial expressions compared with low BMI. No differences between groups were detected for the subjective pleasantness and familiarity. The research here is the first to examine how affective facial reactions to bitter food, apart from taste responsiveness, can predict differences in BMI. Copyright © 2013 Elsevier Ltd. All rights reserved.
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The effects of proton exposure on neurochemistry and behavior
NASA Technical Reports Server (NTRS)
Shukitt-Hale, B.; Szprengiel, A.; Pluhar, J.; Rabin, B. M.; Joseph, J. A.
2004-01-01
Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints. Published by Elsevier Ltd on behalf of COSPAR.
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Spatial learning and memory deficits induced by exposure to iron-56-particle radiation
NASA Technical Reports Server (NTRS)
Shukitt-Hale, B.; Casadesus, G.; McEwen, J. J.; Rabin, B. M.; Joseph, J. A.
2000-01-01
It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.
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Viggiano, Davide; Vallone, Daniela; Welzl, Hans; Sadile, Adolfo G
2002-09-01
The Naples High- (NHE) and Low-Excitability (NLE) rat lines have been selected since 1976 on the basis of behavioral arousal to novelty (Làt-maze). Selective breeding has been conducted under continuous genetic pressure, with no brother-sister mating. The behavioral analyses presented here deal with (1) activity in environments of different complexity, i.e., holeboard and Làt maze; (2) maze learning in hexagonal tunnel, Olton, and Morris water mazes and; (3) two-way active avoidance and conditioned taste aversion tests. Morphometric analyses deal with central dopaminergic systems at their origin and target sites, as well as the density of dopamine transporter immunoreactivity. Molecular biology analyses are also presented, dealing with recent experiments on the prefrontal cortex (PFc), cloning and identifying differentially expressed genes using subtractive libraries and RNAase protection. The divergence between NLE and NHE rats varies as a function of the complexity level of the environment, with an impaired working and reference memory in both lines compared to random bred (NRB) controls. Moreover, data from the PFc of NHE rats show a hyperdopaminergic innervation, with overexpression of mRNA species involved in basal metabolism, and down-regulation of dopamine D1 receptors. Altogether, the evidence gathered so far supports a hyperfunctioning mesocorticolimbic system that makes NHE rats a useful tool for the study of hyperactivity and attention deficit, learning and memory disabilities, and drug abuse.
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Pelloux, Yann; Hagues, Guillaume; Costentin, Jean; Duterte-Boucher, Dominique
2005-03-01
Depression is frequently observed in drug abusers. However, depression may be a primary factor of predisposition to drug abuse or a consequence of drug abuse. The aim of this study was to analyze the influence of a preexisting depressive-like state/helplessness on subsequent alcohol responsiveness in mice. Male and female CD1 mice were selected according to their immobility time in the tail suspension test, and only mice with "high immobility" and "low immobility" time were retained. Using a two-bottle free-choice paradigm, these mice were given continuous access to tap water or solutions of ethanol (3-20% v/v), quinine (12.5-50 mg/liter), or sucrose (1-4% w/v). In female mice, rewarding and aversive effects of ethanol (1.5 and 3 g/kg, intraperitoneally) were also investigated using the conditioned place preference and the conditioned taste aversion paradigms. Female mice were more immobile and drank more ethanol than male mice. No striking sex difference was observed in quinine consumption. Sucrose intake was higher in female than in male mice, whatever the solution concentration. At the 4% concentrated solution, a sucrose-induced increase in daily fluid intake was observed only in female mice. Female mice with high immobility time (HI) consumed more ethanol at the highest concentration than female mice with low immobility time (LI), whereas no difference was observed between HI and LI male mice. Moreover, whereas LI female mice failed to express place conditioning induced by the 3-g/kg dose of ethanol, HI female mice were strongly responsive to the rewarding effect of this high ethanol dose. Ethanol dose-dependently induced a conditioned taste aversion with a similar magnitude in both LI and HI female mice. The findings indicate that female CD1 mice tend to drink greater amounts of ethanol or sucrose solutions than male CD1 mice, suggesting that female mice may be a better model of excessive alcohol intake. Furthermore, no relationship was found between immobility scores and ethanol consumption in male mice. On the contrary, within female mice, HI mice consumed higher amounts of ethanol than LI mice probably because they experienced greater rewarding effects of ethanol. The present results support the hypothesis that depressive-like responses may predispose to ethanol abuse in female mice.
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NASA Astrophysics Data System (ADS)
Anderhag, P.; Wickman, P.-O.; Hamza, K. M.
2015-06-01
In this paper we present a methodological approach for analyzing the transformation of interest in science through classroom talk and action. To this end, we use the construct of taste for science as a social and communicative operationalization, or proxy, to the more psychologically oriented construct of interest. To gain a taste for science as part of school science activities means developing habits of performing and valuing certain distinctions about ways to talk, act and be that are jointly construed as belonging in the school science classroom. In this view, to learn science is not only about learning the curriculum content, but also about learning a normative and aesthetic content in terms of habits of distinguishing and valuing. The approach thus complements previous studies on students' interest in science, by making it possible to analyze how taste for science is constituted, moment-by-moment, through talk and action in the science classroom. In developing the method, we supplement theoretical constructs coming from pragmatism and Pierre Bourdieu with empirical data from a lower secondary science classroom. The application of the method to this classroom demonstrates the potential that the approach has for analyzing how conceptual, normative, and aesthetic distinctions within the science classroom interact in the constitution of taste for, and thereby potentially also in the development of interest in science among students.
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Genetics of sweet taste preferences†
Bachmanov, Alexander A; Bosak, Natalia P; Floriano, Wely B; Inoue, Masashi; Li, Xia; Lin, Cailu; Murovets, Vladimir O; Reed, Danielle R; Zolotarev, Vasily A; Beauchamp, Gary K
2011-01-01
Sweet taste is a powerful factor influencing food acceptance. There is considerable variation in sweet taste perception and preferences within and among species. Although learning and homeostatic mechanisms contribute to this variation in sweet taste, much of it is genetically determined. Recent studies have shown that variation in the T1R genes contributes to within- and between-species differences in sweet taste. In addition, our ongoing studies using the mouse model demonstrate that a significant portion of variation in sweetener preferences depends on genes that are not involved in peripheral taste processing. These genes are likely involved in central mechanisms of sweet taste processing, reward and/or motivation. Genetic variation in sweet taste not only influences food choice and intake, but is also associated with proclivity to drink alcohol. Both peripheral and central mechanisms of sweet taste underlie correlation between sweet-liking and alcohol consumption in animal models and humans. All these data illustrate complex genetics of sweet taste preferences and its impact on human nutrition and health. Identification of genes responsible for within- and between-species variation in sweet taste can provide tools to better control food acceptance in humans and other animals. PMID:21743773
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ERIC Educational Resources Information Center
Holland, Peter C.
2008-01-01
In experiments that measured food consumption, Holland (1981; "Learning and Motivation," 12, 1-18) found that food aversions were formed when an exteroceptive associate of food was paired with illness, but not when such an associate was paired with shock. By contrast, measuring the ability of food to reinforce instrumental responding,…
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ERIC Educational Resources Information Center
Huh, Kyu Hwan; Guzman, Yomayra F.; Tronson, Natalie C.; Guedea, Anita L.; Gao, Can; Radulovic, Jelena
2009-01-01
Extinction of fear requires learning that anticipated aversive events no longer occur. Animal models reveal that sustained phosphorylation of the extracellular signal-regulated kinase (Erk) in hippocampal CA1 neurons plays an important role in this process. However, the key signals triggering and regulating the activity of Erk are not known. By…
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ERIC Educational Resources Information Center
Tinsley, Matthew R.; Quinn, Jennifer J.; Fanselow, Michael S.
2004-01-01
Aversive conditioning is an ideal model for studying cholinergic effects on the processes of learning and memory for several reasons. First, deficits produced by selective lesions of the anatomical structures shown to be critical for Pavlovian fear conditioning and inhibitory avoidance (such as the amygdala and hippocampus) resemble those deficits…
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ERIC Educational Resources Information Center
Kimbrough, Adam; Kwon, Bumsup; Eckel, Lisa A.; Houpt, Thomas A.
2011-01-01
5-bromo-2-deoxyuridine (BrdU) is often used in studies of adult neurogenesis and olfactory learning, but it can also have toxic effects on highly proliferative tissue. We found that pairing Kool-Aid flavors with acute systemic injections of BrdU induced strong conditioned flavor aversions. Intermittent injections during Kool-Aid-glucose…
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What a relief! A role for dopamine in positive (but not negative) valence.
Sharpe, Melissa J
2018-02-27
We have long known that dopamine encodes the predictive relationship between cues and rewards. But what about relief learning? In this issue of Neuropsychopharmacology, Meyer et al. show that the same circuits encoding rewarding events also encode relief from aversive events. And this appears to be in a manner distinct from encoding of the aversive event itself. So does dopamine only contribute to learning about positive events? And are these events encoded in the same way regardless of how that positive experience came about? Not quite. Turns out, the devil is in the details.
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Response to palatability after area postrema lesions: a result of learned aversions.
Tomoyasu, N; Kenney, N J
1989-11-01
The role of palatability, novelty, and food aversion in determining changes of food choice after ablation of the area postrema and caudal-medial aspect of the nucleus of the solitary tract (AP/cmNTS) is examined through a series of studies utilizing 24-h, two-food choice tests. On test days, the food that the animal has ingested since the time of lesioning or sham surgery is presented along with a novel food that varies in palatability. The results indicate that postlesion diet history is the major determinant of food choice by lesioned rats. Lesioned rats consistently take less of their familiar postlesion food than diet-matched controls, suggesting that the lesioned rats have developed an aversion to that food. Over-ingestion of the novel food may occur, but this outcome is not reliable. No indication that the animals' response to food palatability is affected by AP/cmNTS ablation was found. Learned aversion to a food ingested after AP/cmNTS ablation may account not only for changes of food preference after the lesion but also may be involved in the hypophagia and weight loss resulting from the ablation.
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Opponent appetitive-aversive neural processes underlie predictive learning of pain relief.
Seymour, Ben; O'Doherty, John P; Koltzenburg, Martin; Wiech, Katja; Frackowiak, Richard; Friston, Karl; Dolan, Raymond
2005-09-01
Termination of a painful or unpleasant event can be rewarding. However, whether the brain treats relief in a similar way as it treats natural reward is unclear, and the neural processes that underlie its representation as a motivational goal remain poorly understood. We used fMRI (functional magnetic resonance imaging) to investigate how humans learn to generate expectations of pain relief. Using a pavlovian conditioning procedure, we show that subjects experiencing prolonged experimentally induced pain can be conditioned to predict pain relief. This proceeds in a manner consistent with contemporary reward-learning theory (average reward/loss reinforcement learning), reflected by neural activity in the amygdala and midbrain. Furthermore, these reward-like learning signals are mirrored by opposite aversion-like signals in lateral orbitofrontal cortex and anterior cingulate cortex. This dual coding has parallels to 'opponent process' theories in psychology and promotes a formal account of prediction and expectation during pain.
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Evaluation of ambiguous associations in the amygdala by learning the structure of the environment
Madarasz, Tamas J.; Diaz-Mataix, Lorenzo; Akhand, Omar; Ycu, Edgar A.; LeDoux, Joseph E.; Johansen, Joshua P.
2017-01-01
Recognizing predictive relationships is critical for survival, but an understanding of the underlying neural mechanisms remains elusive. In particular it is unclear how the brain distinguishes predictive relationships from spurious ones when evidence about a relationship is ambiguous, or how it computes predictions given such uncertainty. To better understand this process we introduced ambiguity into an associative learning task by presenting aversive outcomes both in the presence and absence of a predictive cue. Electrophysiological and optogenetic approaches revealed that amygdala neurons directly regulate and track the effects of ambiguity on learning. Contrary to established accounts of associative learning however, interference from competing associations was not required to assess an ambiguous cue-outcome contingency. Instead, animals’ behavior was explained by a normative account that evaluates different models of the environment’s statistical structure. These findings suggest an alternative view on the role of amygdala circuits in resolving ambiguity during aversive learning. PMID:27214568
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Evaluation of ambiguous associations in the amygdala by learning the structure of the environment.
Madarasz, Tamas J; Diaz-Mataix, Lorenzo; Akhand, Omar; Ycu, Edgar A; LeDoux, Joseph E; Johansen, Joshua P
2016-07-01
Recognizing predictive relationships is critical for survival, but an understanding of the underlying neural mechanisms remains elusive. In particular, it is unclear how the brain distinguishes predictive relationships from spurious ones when evidence about a relationship is ambiguous, or how it computes predictions given such uncertainty. To better understand this process, we introduced ambiguity into an associative learning task by presenting aversive outcomes both in the presence and in the absence of a predictive cue. Electrophysiological and optogenetic approaches revealed that amygdala neurons directly regulated and tracked the effects of ambiguity on learning. Contrary to established accounts of associative learning, however, interference from competing associations was not required to assess an ambiguous cue-outcome contingency. Instead, animals' behavior was explained by a normative account that evaluates different models of the environment's statistical structure. These findings suggest an alternative view of amygdala circuits in resolving ambiguity during aversive learning.
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The habenula encodes negative motivational value associated with primary punishment in humans.
Lawson, Rebecca P; Seymour, Ben; Loh, Eleanor; Lutti, Antoine; Dolan, Raymond J; Dayan, Peter; Weiskopf, Nikolaus; Roiser, Jonathan P
2014-08-12
Learning what to approach, and what to avoid, involves assigning value to environmental cues that predict positive and negative events. Studies in animals indicate that the lateral habenula encodes the previously learned negative motivational value of stimuli. However, involvement of the habenula in dynamic trial-by-trial aversive learning has not been assessed, and the functional role of this structure in humans remains poorly characterized, in part, due to its small size. Using high-resolution functional neuroimaging and computational modeling of reinforcement learning, we demonstrate positive habenula responses to the dynamically changing values of cues signaling painful electric shocks, which predict behavioral suppression of responses to those cues across individuals. By contrast, negative habenula responses to monetary reward cue values predict behavioral invigoration. Our findings show that the habenula plays a key role in an online aversive learning system and in generating associated motivated behavior in humans.
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Bergado Acosta, Jorge R; Schneider, Miriam; Fendt, Markus
2017-10-01
Humans and animals are able to associate an environmental cue with the feeling of relief from an aversive event, a phenomenon called relief learning. Relief from an aversive event is rewarding and a relief-associated cue later induces an attenuation of the startle magnitude or approach behavior. Previous studies demonstrated that the nucleus accumbens is essential for relief learning. Here, we asked whether accumbal cannabinoid type 1 (CB1) receptors are involved in relief learning. In rats, we injected the CB1 receptor antagonist/inverse agonist SR141716A (rimonabant) directly into the nucleus accumbens at different time points during a relief learning experiment. SR141716A injections immediately before the conditioning inhibited relief learning. However, SR141716A injected immediately before the retention test was not effective when conditioning was without treatment. These findings indicate that accumbal CB1 receptors play an important role in the plasticity processes underlying relief learning. Copyright © 2017 Elsevier Inc. All rights reserved.
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Boersma, Gretha J; Treesukosol, Yada; Cordner, Zachary A; Kastelein, Anneke; Choi, Pique; Moran, Timothy H; Tamashiro, Kellie L
2016-02-01
Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period. Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered. Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference. © 2015 Wiley Periodicals, Inc.
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Wetzel, Wolfram; Scheich, Henning; Ohl, Frank W.
2013-01-01
The lateral habenula (LHb) is an epithalamic structure involved in signaling reward omission and aversive stimuli, and it inhibits dopaminergic neurons during motivated behavior. Less is known about LHb involvement in the acquisition and retrieval of avoidance learning. Our previous studies indicated that brief electrical stimulation of the LHb, time-locked to the avoidance of aversive footshock (presumably during the positive affective “relief” state that occurs when an aversive outcome is averted), inhibited the acquisition of avoidance learning. In the present study, we used the same paradigm to investigate different frequencies of LHb stimulation. The effect of 20 Hz vs. 50 Hz vs. 100 Hz stimulation was investigated during two phases, either during acquisition or retrieval in Mongolian gerbils. The results indicated that 50 Hz, but not 20 Hz, was sufficient to produce a long-term impairment in avoidance learning, and was somewhat more effective than 100 Hz in this regard. None of the stimulation parameters led to any effects on retrieval of avoidance learning, nor did they affect general motor activity. This suggests that, at frequencies in excess of the observed tonic firing rates of LHb neurons (>1–20 Hz), LHb stimulation may serve to interrupt the consolidation of new avoidance memories. However, these stimulation parameters are not capable of modifying avoidance memories that have already undergone extensive consolidation. PMID:23840355
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Worrying affects associative fear learning: a startle fear conditioning study.
Gazendam, Femke J; Kindt, Merel
2012-01-01
A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS) and an anticipated disaster (Unconditioned Stimulus, UCS). Most anxiety disorders, however, do not evolve from a traumatic experience. Insights from neuroscience show that memory can be modified post-learning, which may elucidate how pathological fear can develop after relatively mild aversive events. Worrying--a process frequently observed in anxiety disorders--is a potential candidate to strengthen the formation of fear memory after learning. Here we tested in a discriminative fear conditioning procedure whether worry strengthens associative fear memory. Participants were randomly assigned to either a Worry (n = 23) or Control condition (n = 25). After fear acquisition, the participants in the Worry condition processed six worrisome questions regarding the personal aversive consequences of an electric stimulus (UCS), whereas the Control condition received difficult but neutral questions. Subsequently, extinction, reinstatement and re-extinction of fear were tested. Conditioned responding was measured by fear-potentiated startle (FPS), skin conductance (SCR) and UCS expectancy ratings. Our main results demonstrate that worrying resulted in increased fear responses (FPS) to both the feared stimulus (CS(+)) and the originally safe stimulus (CS(-)), whereas FPS remained unchanged in the Control condition. In addition, worrying impaired both extinction and re-extinction learning of UCS expectancy. The implication of our findings is that they show how worry may contribute to the development of anxiety disorders by affecting associative fear learning.
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Pizzagalli, Diego A; Greischar, Lawrence L; Davidson, Richard J
2003-01-01
Social cognition, including complex social judgments and attitudes, is shaped by individual learning experiences, where affect often plays a critical role. Aversive classical conditioning-a form of associative learning involving a relationship between a neutral event (conditioned stimulus, CS) and an aversive event (unconditioned stimulus, US)-represents a well-controlled paradigm to study how the acquisition of socially relevant knowledge influences behavior and the brain. Unraveling the temporal unfolding of brain mechanisms involved appears critical for an initial understanding about how social cognition operates. Here, 128-channel ERPs were recorded in 50 subjects during the acquisition phase of a differential aversive classical conditioning paradigm. The CS+ (two fearful faces) were paired 50% of the time with an aversive noise (CS upward arrow + /Paired), whereas in the remaining 50% they were not (CS upward arrow + /Unpaired); the CS- (two different fearful faces) were never paired with the noise. Scalp ERP analyses revealed differences between CS upward arrow + /Unpaired and CS- as early as approximately 120 ms post-stimulus. Tomographic source localization analyses revealed early activation modulated by the CS+ in the ventral visual pathway (e.g. fusiform gyrus, approximately 120 ms), right middle frontal gyrus (approximately 176 ms), and precuneus (approximately 240 ms). At approximately 120 ms, the CS- elicited increased activation in the left insula and left middle frontal gyrus. These findings not only confirm a critical role of prefrontal, insular, and precuneus regions in aversive conditioning, but they also suggest that biologically and socially salient information modulates activation at early stages of the information processing flow, and thus furnish initial insight about how affect and social judgments operate.
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Potentiation of the early visual response to learned danger signals in adults and adolescents
Howsley, Philippa; Jordan, Jeff; Johnston, Pat
2015-01-01
The reinforcing effects of aversive outcomes on avoidance behaviour are well established. However, their influence on perceptual processes is less well explored, especially during the transition from adolescence to adulthood. Using electroencephalography, we examined whether learning to actively or passively avoid harm can modulate early visual responses in adolescents and adults. The task included two avoidance conditions, active and passive, where two different warning stimuli predicted the imminent, but avoidable, presentation of an aversive tone. To avoid the aversive outcome, participants had to learn to emit an action (active avoidance) for one of the warning stimuli and omit an action for the other (passive avoidance). Both adults and adolescents performed the task with a high degree of accuracy. For both adolescents and adults, increased N170 event-related potential amplitudes were found for both the active and the passive warning stimuli compared with control conditions. Moreover, the potentiation of the N170 to the warning stimuli was stable and long lasting. Developmental differences were also observed; adolescents showed greater potentiation of the N170 component to danger signals. These findings demonstrate, for the first time, that learned danger signals in an instrumental avoidance task can influence early visual sensory processes in both adults and adolescents. PMID:24652856
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Scholl, Jacqueline; Kolling, Nils; Nelissen, Natalie; Browning, Michael; Rushworth, Matthew F S; Harmer, Catherine J
2017-02-01
To make good decisions, humans need to learn about and integrate different sources of appetitive and aversive information. While serotonin has been linked to value-based decision-making, its role in learning is less clear, with acute manipulations often producing inconsistent results. Here, we show that when the effects of a selective serotonin reuptake inhibitor (SSRI, citalopram) are studied over longer timescales, learning is robustly improved. We measured brain activity with functional magnetic resonance imaging (fMRI) in volunteers as they performed a concurrent appetitive (money) and aversive (effort) learning task. We found that 2 weeks of citalopram enhanced reward and effort learning signals in a widespread network of brain regions, including ventromedial prefrontal and anterior cingulate cortex. At a behavioral level, this was accompanied by more robust reward learning. This suggests that serotonin can modulate the ability to learn via a mechanism that is independent of stimulus valence. Such effects may partly underlie SSRIs' impact in treating psychological illnesses. Our results highlight both a specific function in learning for serotonin and the importance of studying its role across longer timescales.
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Vargas-Perez, Hector; Ting-A-Kee, Ryan A; Heinmiller, Andrew; Sturgess, Jessica E; van der Kooy, Derek
2007-06-01
The opponent-process theory of motivation postulates that motivational stimuli activate a rewarding process that is followed by an opposed aversive process in a homeostatic control mechanism. Thus, an acute injection of morphine in nondependent animals should evoke an acute rewarding response, followed by a later aversive response. Indeed, the tegmental pedunculopontine nucleus (TPP) mediates the rewarding effects of opiates in previously morphine-naive animals, but not other unconditioned effects of opiates, or learning ability. The aversive opponent process for acute morphine reward was revealed using a place-conditioning paradigm. The conditioned place aversion induced by 16-h spontaneous morphine withdrawal from an acute morphine injection in nondependent rats was abolished by TPP lesions performed prior to drug experience. However, TPP-lesioned rats did show conditioned aversions for an environment paired with the acute administration of the opioid antagonist naloxone, which blocks endogenous opioids. The results show that blocking the rewarding effects of morphine with TPP lesions also blocked the opponent aversive effects of acute morphine withdrawal in nondependent animals. Thus, this spontaneous withdrawal aversion (the opponent process) is induced by the acute rewarding effects of morphine and not by other unconditioned effects of morphine, the pharmacological effects of morphine or endogenous opioids being displaced from opiate receptors.
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Atlas, Lauren Y; Doll, Bradley B; Li, Jian; Daw, Nathaniel D; Phelps, Elizabeth A
2016-01-01
Socially-conveyed rules and instructions strongly shape expectations and emotions. Yet most neuroscientific studies of learning consider reinforcement history alone, irrespective of knowledge acquired through other means. We examined fear conditioning and reversal in humans to test whether instructed knowledge modulates the neural mechanisms of feedback-driven learning. One group was informed about contingencies and reversals. A second group learned only from reinforcement. We combined quantitative models with functional magnetic resonance imaging and found that instructions induced dissociations in the neural systems of aversive learning. Responses in striatum and orbitofrontal cortex updated with instructions and correlated with prefrontal responses to instructions. Amygdala responses were influenced by reinforcement similarly in both groups and did not update with instructions. Results extend work on instructed reward learning and reveal novel dissociations that have not been observed with punishments or rewards. Findings support theories of specialized threat-detection and may have implications for fear maintenance in anxiety. DOI: http://dx.doi.org/10.7554/eLife.15192.001 PMID:27171199
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Early Life Manipulations Alter Learning and Memory in Rats
Kosten, Therese A; Kim, Jeansok J; Lee, Hongjoo J.
2012-01-01
Much research shows early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational memory also depended upon timing of manipulation. Enhanced performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. PMID:22819985
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Is there evidence of learned helplessness in horses?
Hall, Carol; Goodwin, Deborah; Heleski, Camie; Randle, Hayley; Waran, Natalie
2008-01-01
Learned helplessness is a psychological condition whereby individuals learn that they have no control over unpleasant or harmful conditions, that their actions are futile, and that they are helpless. In a series of experiments in which dogs were exposed to inescapable shocks, this lack of control subsequently interfered with the ability to learn an avoidance task. There is evidence that both neural adaptations and behavioral despair occur in response to uncontrollable aversive experiences in rodents, although this has yet to be demonstrated in other species such as horses. However, certain traditional methods of horse training and some behavioral modification techniques--it has been suggested--may involve aversive conditions over which the horse has little or no control. When training and management procedures are repeatedly unpleasant for the horse and there is no clear association between behavior and outcome, this is likely to interfere with learning and performance-in addition to compromising welfare. This article reviews published literature and anecdotal evidence to explore the possibility that the phenomenon, learned helplessness, occurs in the horse.
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NASA Astrophysics Data System (ADS)
Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.
2004-01-01
Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.
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NASA Technical Reports Server (NTRS)
Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.
2004-01-01
Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.
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Martin, Bronwen; Wang, Rui; Cong, Wei-Na; Daimon, Caitlin M; Wu, Wells W; Ni, Bin; Becker, Kevin G; Lehrmann, Elin; Wood, William H; Zhang, Yongqing; Etienne, Harmonie; van Gastel, Jaana; Azmi, Abdelkrim; Janssens, Jonathan; Maudsley, Stuart
2017-07-07
The type 1 taste receptor member 3 (T1R3) is a G protein-coupled receptor involved in sweet-taste perception. Besides the tongue, the T1R3 receptor is highly expressed in brain areas implicated in cognition, including the hippocampus and cortex. As cognitive decline is often preceded by significant metabolic or endocrinological dysfunctions regulated by the sweet-taste perception system, we hypothesized that a disruption of the sweet-taste perception in the brain could have a key role in the development of cognitive dysfunction. To assess the importance of the sweet-taste receptors in the brain, we conducted transcriptomic and proteomic analyses of cortical and hippocampal tissues isolated from T1R3 knock-out (T1R3KO) mice. The effect of an impaired sweet-taste perception system on cognition functions were examined by analyzing synaptic integrity and performing animal behavior on T1R3KO mice. Although T1R3KO mice did not present a metabolically disrupted phenotype, bioinformatic interpretation of the high-dimensionality data indicated a strong neurodegenerative signature associated with significant alterations in pathways involved in neuritogenesis, dendritic growth, and synaptogenesis. Furthermore, a significantly reduced dendritic spine density was observed in T1R3KO mice together with alterations in learning and memory functions as well as sociability deficits. Taken together our data suggest that the sweet-taste receptor system plays an important neurotrophic role in the extralingual central nervous tissue that underpins synaptic function, memory acquisition, and social behavior. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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Sollai, Giorgia; Tomassini Barbarossa, Iole; Masala, Carla; Solari, Paolo; Crnjar, Roberto
2014-01-01
In herbivorous insects, food selection depends on sensitivity to specific chemical stimuli from host-plants as well as to secondary metabolites (bitter) and to sugars (phagostimulatory). Bitter compounds are noxious, unpalatable or both and evoke an aversive feeding response. Instead, sugars and sugar alcohols play a critical role in determining and enhancing the palatability of foods. We assumed that peripheral taste sensitivity may be related to the width of the host selection. Our model consists of two closely phylogenetically related Papilionid species exhibiting a difference in host plant choice: Papilio hospiton and Papilio machaon. The spike activity of the lateral and medial maxillary styloconic taste sensilla was recorded following stimulation with several carbohydrates, nicotine and NaCl, with the aim of characterizing their gustatory receptor neurons and of comparing their response patterns in the light of their different acceptability in feeding behaviour. The results show that: a) each sensillum houses phagostimulant and phagodeterrent cells; b) the spike activity of the gustatory neurons in response to different taste stimuli is higher in P. hospiton than in P. machaon; c) sugar solutions inhibit the spike activity of the deterrent and salt cells, and the suppression is higher in P. machaon than in P. hospiton. In conclusion, we propose that the different balance between the phagostimulant and phagodeterrent inputs from GRNs of maxillary sensilla may contribute in determining the difference in food choice and host range.
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Sollai, Giorgia; Tomassini Barbarossa, Iole; Masala, Carla; Solari, Paolo; Crnjar, Roberto
2014-01-01
In herbivorous insects, food selection depends on sensitivity to specific chemical stimuli from host-plants as well as to secondary metabolites (bitter) and to sugars (phagostimulatory). Bitter compounds are noxious, unpalatable or both and evoke an aversive feeding response. Instead, sugars and sugar alcohols play a critical role in determining and enhancing the palatability of foods. We assumed that peripheral taste sensitivity may be related to the width of the host selection. Our model consists of two closely phylogenetically related Papilionid species exhibiting a difference in host plant choice: Papilio hospiton and Papilio machaon. The spike activity of the lateral and medial maxillary styloconic taste sensilla was recorded following stimulation with several carbohydrates, nicotine and NaCl, with the aim of characterizing their gustatory receptor neurons and of comparing their response patterns in the light of their different acceptability in feeding behaviour. The results show that: a) each sensillum houses phagostimulant and phagodeterrent cells; b) the spike activity of the gustatory neurons in response to different taste stimuli is higher in P. hospiton than in P. machaon; c) sugar solutions inhibit the spike activity of the deterrent and salt cells, and the suppression is higher in P. machaon than in P. hospiton. In conclusion, we propose that the different balance between the phagostimulant and phagodeterrent inputs from GRNs of maxillary sensilla may contribute in determining the difference in food choice and host range. PMID:24956387
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Aversion of the cat to dietary medium-chain triglycerides and caprylic acid.
MacDonald, M L; Rogers, Q R; Morris, J G
1985-09-01
Young, specific-pathogen-free cats were fed purified diets containing different sources of fat. Food intake was depressed and cats lost weight when the diet contained either hydrogenated coconut oil (HCO) or medium-chain triglycerides (MCT). With an MCT preparation enriched in 8:0 (MCT8), cats would not eat after first tasting the diet. When cats were offered a choice of two high-fat diets, they chose the basal diet over a diet containing 30% HCO, by a ratio of 4.5:1. Low levels of MCT8 (5% or 10% by weight) were also rejected, whereas cats did not reject 5% or 15% MCT12. Caprylic acid, at 0.1-1.0% of the diet, was rejected. In other studies, food intake and body weight decreased when HCO was added to a fat-free diet. Cats fed 25% or 35% HCO lost weight. When 5% safflower seed oil was added to the HCO diets, body weights and food intake improved, but were still less than optimal. These studies indicate that the food intake depression in cats fed dietary HCO and MCT is primarily a result of impalatability, and that the fatty acid moiety may be responsible for the aversion.
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Wegerer, Melanie; Blechert, Jens; Kerschbaum, Hubert; Wilhelm, Frank H.
2013-01-01
Intrusive memories – a hallmark symptom of posttraumatic stress disorder (PTSD) – are often triggered by stimuli possessing similarity with cues that predicted or accompanied the traumatic event. According to learning theories, intrusive memories can be seen as a conditioned response to trauma reminders. However, direct laboratory evidence for the link between fear conditionability and intrusive memories is missing. Furthermore, fear conditioning studies have predominantly relied on standardized aversive stimuli (e.g. electric stimulation) that bear little resemblance to typical traumatic events. To investigate the general relationship between fear conditionability and aversive memories, we tested 66 mentally healthy females in a novel conditioned-intrusion paradigm designed to model real-life traumatic experiences. The paradigm included a differential fear conditioning procedure with neutral sounds as conditioned stimuli and short violent film clips as unconditioned stimuli. Subsequent aversive memories were assessed through a memory triggering task (within 30 minutes, in the laboratory) and ambulatory assessment (involuntary aversive memories in the 2 days following the experiment). Skin conductance responses and subjective ratings demonstrated successful differential conditioning indicating that naturalistic aversive film stimuli can be used in a fear conditioning experiment. Furthermore, aversive memories were elicited in response to the conditioned stimuli during the memory triggering task and also occurred in the 2 days following the experiment. Importantly, participants who displayed higher conditionability showed more aversive memories during the memory triggering task and during ambulatory assessment. This suggests that fear conditioning constitutes an important source of persistent aversive memories. Implications for PTSD and its treatment are discussed. PMID:24244407
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Fabrication of taste sensor for education
NASA Astrophysics Data System (ADS)
Wu, Xiao; Tahara, Yusuke; Toko, Kiyoshi; Kuriyaki, Hisao
2017-03-01
In order to solve the unconcern to usefulness of learning science among high school students in Japan, we developed a simple fabricated taste sensor with sensitivity and selectivity to each taste quality, which can be applied in science class. A commercialized Teflon membrane was used as the polymer membrane holding lipids. In addition, a non-adhesive method is considered to combine the membrane and the sensor electrode using a plastic cap which is easily accessible. The taste sensor for education fabricated in this way showed a good selectivity and sensitivity. By adjusting the composition of trioctylmethylammonium chloride (TOMA) and phosphoric acid di(2-ethylhexyl) ester (PAEE) included in lipid solution, we improved the selectivity of this simple taste sensor to saltiness and sourness. To verify this taste sensor as a useful science teaching material for science class, we applied this taste sensor into a science class for university students. By comparing the results between the sensory test and the sensor response, humans taste showed the same tendency just as the sensor response, which proved the sensor as a useful teaching material for science class.
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Bortolatto, Cristiani F; Heck, Suélen O; Zborowski, Vanessa A; Gai, Bibiana M; Neto, José S S; Nogueira, Cristina W
2015-11-01
Preliminary findings suggest that food intake reduction induced by p-chloro-diphenyl diselenide [(p-ClPhSe)2] in rats is mediated by a satiating action; however, additional experiments are necessary to clarify its actions. The purpose of this study was to investigate the effects of diets supplemented with (p-ClPhSe)2 on feeding behavior of rats as well as the (p-ClPhSe)2 effectiveness in producing aversive reactions or specific flavor. The results demonstrated that behavioral satiety sequence (BSS) was preserved in animals exposed to (p-ClPhSe)2-supplemented diets (0.01 and 0.1%) and associated with a shift of the onset of resting to the left indicating a satiating action at the first contact. In addition, the frequency, the mean duration and the mean size of meals were decreased in rats exposed to a 0.1% (p-ClPhSe)2 diet. Alternatively, a second contact with a 0.01% (p-ClPhSe)2 diet caused disruption of BSS and pronounced changes in the meal pattern, suggesting that it produces aversiveness. In fact, rats developed a significant taste aversion to the saccharin solution after receiving the administration of (p-ClPhSe)2 (1 and 10mg/kg; i.p.). Lastly, a diet containing 0.1% of (p-ClPhSe)2 seems to alter the palatability of food given that rats had a preference for the control diet. The findings of the present study suggest that (p-ClPhSe)2 reduced the food intake of rats by inducing a satiating action at the first contact, but it also produced aversive reactions when rats were re-exposed to it. A specific flavor seems also to contribute to (p-ClPhSe)2 suppressant effects on feeding. Copyright © 2015 Elsevier Inc. All rights reserved.
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Perceived ambiguity as a barrier to intentions to learn genome sequencing results
Taber, Jennifer M.; Klein, William M.P.; Ferrer, Rebecca A.; Han, Paul K. J.; Lewis, Katie L.; Biesecker, Leslie G.; Biesecker, Barbara B.
2015-01-01
Many variants that could be returned from genome sequencing may be perceived as ambiguous—lacking reliability, credibility, or adequacy. Little is known about how perceived ambiguity influences thoughts about sequencing results. Participants (n=494) in an NIH genome sequencing study completed a baseline survey before sequencing results were available. We examined how perceived ambiguity regarding sequencing results and individual differences in medical ambiguity aversion and tolerance for uncertainty were associated with cognitions and intentions concerning sequencing results. Perceiving sequencing results as more ambiguous was associated with less favorable cognitions about results and lower intentions to learn and share results. Among participants low in tolerance for uncertainty or optimism, greater perceived ambiguity was associated with lower intentions to learn results for non-medically actionable diseases; medical ambiguity aversion did not moderate any associations. Results are consistent with the phenomenon of “ambiguity aversion” and may influence whether people learn and communicate genomic information. PMID:26003053
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Taste-immunosuppression engram: reinforcement and extinction.
Niemi, Maj-Britt; Härting, Margarete; Kou, Wei; Del Rey, Adriana; Besedovsky, Hugo O; Schedlowski, Manfred; Pacheco-López, Gustavo
2007-08-01
Several Pavlovian conditioning paradigms have documented the brain's abilities to sense immune-derived signals or immune status, associate them with concurrently relevant extereoceptive stimuli, and reinstate such immune responses on demand. Specifically, the naturalistic relation of food ingestion with its possible immune consequences facilitates taste-immune associations. Here we demonstrate that the saccharin taste can be associated with the immunosuppressive agent cyclosporine A, and that such taste-immune associative learning is subject to reinforcement. Furthermore, once consolidated, this saccharin-immunosuppression engram is resistant to extinction when avoidance behavior is assessed. More importantly, the more this engram is activated, either at association or extinction phases, the more pronounced is the conditioned immunosuppression.
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Placek, Caitlyn D; Madhivanan, Purnima; Hagen, Edward H
2017-11-01
Pregnancy increases women's nutritional requirements, yet causes aversions to nutritious foods. Most societies further restrict pregnant women's diet with food taboos. Pregnancy food aversions are theorized to protect mothers and fetuses from teratogens and pathogens or increase dietary diversity in response to resource scarcity. Tests of these hypotheses have had mixed results, perhaps because many studies are in Westernized populations with reliable access to food and low exposure to pathogens. If pregnancy food aversions are adaptations, however, then they likely evolved in environments with uncertain access to food and high exposure to pathogens. Pregnancy food taboos, on the other hand, have been theorized to limit resource consumption, mark social identity, or also protect mothers and fetuses from dangerous foods. There have been few tests of evolutionary theories of culturally transmitted food taboos. We investigated these and other theories of psychophysiological food aversions and culturally transmitted food taboos among two non-Western populations of pregnant women in Mysore, India, that vary in food insecurity and exposure to infectious disease. The first was a mixed caste rural farming population ( N = 72), and the second was the Jenu Kurubas , a resettled population of former hunter-gatherers ( N = 30). Women rated their aversions to photos of 31 foods and completed structured interviews that assessed aversions and socially learned avoidances of foods, pathogen exposure, food insecurity, sources of culturally acquired dietary advice, and basic sociodemographic information. Aversions to spicy foods were associated with early trimester and nausea and vomiting, supporting a protective role against plant teratogens. Variation in exposure to pathogens did not explain variation in meat aversions or avoidances, however, raising some doubts about the importance of pathogen avoidance. Aversions to staple foods were common, but were not associated with resource stress, providing mixed support for the role of dietary diversification. Avoided foods outnumbered aversive foods, were believed to be abortifacients or otherwise harmful to the fetus, influenced diet throughout pregnancy, and were largely distinct from aversive foods. These results suggest that aversions target foods with cues of toxicity early in pregnancy, and taboos target suspected abortifacients throughout pregnancy.
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One-trial overshadowing: Evidence for fast specific fear learning in humans.
Haesen, Kim; Beckers, Tom; Baeyens, Frank; Vervliet, Bram
2017-03-01
Adaptive defensive actions necessitate a fear learning system that is both fast and specific. Fast learning serves to minimize the number of threat confrontations, while specific learning ensures that the acquired fears are tied to threat-relevant cues only. In Pavlovian fear conditioning, fear acquisition is typically studied via repetitive pairings of a single cue with an aversive experience, which is not optimal for the examination of fast specific fear learning. In this study, we adopted the one-trial overshadowing procedure from basic learning research, in which a combination of two visual cues is presented once and paired with an aversive electrical stimulation. Using on-line shock expectancy ratings, skin conductance reactivity and startle reflex modulation as indices of fear learning, we found evidence of strong fear after a single conditioning trial (fast learning) as well as attenuated fear responding when only half of the trained stimulus combination was presented (specific learning). Moreover, specificity of fear responding tended to correlate with levels of state and trait anxiety. These results suggest that one-trial overshadowing can be used as a model to study fast specific fear learning in humans and individual differences therein. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Roles of Aminergic Neurons in Formation and Recall of Associative Memory in Crickets
Mizunami, Makoto; Matsumoto, Yukihisa
2010-01-01
We review recent progress in the study of roles of octopaminergic (OA-ergic) and dopaminergic (DA-ergic) signaling in insect classical conditioning, focusing on our studies on crickets. Studies on olfactory learning in honey bees and fruit-flies have suggested that OA-ergic and DA-ergic neurons convey reinforcing signals of appetitive unconditioned stimulus (US) and aversive US, respectively. Our work suggested that this is applicable to olfactory, visual pattern, and color learning in crickets, indicating that this feature is ubiquitous in learning of various sensory stimuli. We also showed that aversive memory decayed much faster than did appetitive memory, and we proposed that this feature is common in insects and humans. Our study also suggested that activation of OA- or DA-ergic neurons is needed for appetitive or aversive memory recall, respectively. To account for this finding, we proposed a model in which it is assumed that two types of synaptic connections are strengthened by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus (CS) to neurons inducing conditioned response and the other being connections from neurons representing CS to OA- or DA-ergic neurons representing appetitive or aversive US, respectively. The former is called stimulus–response (S–R) connection and the latter is called stimulus–stimulus (S–S) connection by theorists studying classical conditioning in vertebrates. Results of our studies using a second-order conditioning procedure supported our model. We propose that insect classical conditioning involves the formation of S–S connection and its activation for memory recall, which are often called cognitive processes. PMID:21119781
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van der Staay, F Josef; Schuurman, Teun; van Reenen, Cornelis G; Korte, S Mechiel
2009-12-15
Cognitive function might be affected by the subjects' emotional reactivity. We assessed whether behavior in different tests of emotional reactivity is correlated with performance in aversively motivated learning tasks, using four strains of rats generally considered to have a different emotional reactivity. The performance of male Brown Norway, Lewis, Fischer 344, and Wistar Kyoto rats in open field (OF), elevated plus-maze (EPM), and circular light-dark preference box (cLDB) tasks, which are believed to provide measures of emotional reactivity, was evaluated. Spatial working and reference memory were assessed in two aversively motivated learning and memory tasks: the standard and the "repeated acquisition" versions of the Morris water maze escape task, respectively. All rats were also tested in a passive avoidance task. At the end of the study, levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid, and 5-HT turnover in the hippocampus and frontal cortex were determined. Strain differences showed a complex pattern across behavioral tests and serotonergic measures. Fischer 344 rats had the poorest performance in both versions of the Morris water escape task, whereas Brown Norway rats performed these tasks very well but the passive avoidance task poorly. Neither correlation analysis nor principal component analysis provided convincing support for the notion that OF, EPM, and cLDB tasks measure the same underlying trait. Our findings do not support the hypothesis that the level of emotional reactivity modulates cognitive performance in aversively motivated tasks. Concepts such as "emotional reactivity" and "learning and memory" cannot adequately be tapped with only one behavioral test. Our results emphasize the need for multiple testing.
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Junghöfer, Markus; Rehbein, Maimu Alissa; Maitzen, Julius; Schindler, Sebastian
2017-01-01
Abstract Humans have a remarkable capacity for rapid affective learning. For instance, using first-order US such as odors or electric shocks, magnetoencephalography (MEG) studies of multi-CS conditioning demonstrate enhanced early (<150 ms) and mid-latency (150–300 ms) visual evoked responses to affectively conditioned faces, together with changes in stimulus evaluation. However, particularly in social contexts, human affective learning is often mediated by language, a class of complex higher-order US. To elucidate mechanisms of this type of learning, we investigate how face processing changes following verbal evaluative multi-CS conditioning. Sixty neutral expression male faces were paired with phrases about aversive crimes (30) or neutral occupations (30). Post conditioning, aversively associated faces evoked stronger magnetic fields in a mid-latency interval between 220 and 320 ms, localized primarily in left visual cortex. Aversively paired faces were also rated as more arousing and more unpleasant, evaluative changes occurring both with and without contingency awareness. However, no early MEG effects were found, implying that verbal evaluative conditioning may require conceptual processing and does not engage rapid, possibly sub-cortical, pathways. Results demonstrate the efficacy of verbal evaluative multi-CS conditioning and indicate both common and distinct neural mechanisms of first- and higher-order multi-CS conditioning, thereby informing theories of associative learning. PMID:28008078
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Junghöfer, Markus; Rehbein, Maimu Alissa; Maitzen, Julius; Schindler, Sebastian; Kissler, Johanna
2017-04-01
Humans have a remarkable capacity for rapid affective learning. For instance, using first-order US such as odors or electric shocks, magnetoencephalography (MEG) studies of multi-CS conditioning demonstrate enhanced early (<150 ms) and mid-latency (150-300 ms) visual evoked responses to affectively conditioned faces, together with changes in stimulus evaluation. However, particularly in social contexts, human affective learning is often mediated by language, a class of complex higher-order US. To elucidate mechanisms of this type of learning, we investigate how face processing changes following verbal evaluative multi-CS conditioning. Sixty neutral expression male faces were paired with phrases about aversive crimes (30) or neutral occupations (30). Post conditioning, aversively associated faces evoked stronger magnetic fields in a mid-latency interval between 220 and 320 ms, localized primarily in left visual cortex. Aversively paired faces were also rated as more arousing and more unpleasant, evaluative changes occurring both with and without contingency awareness. However, no early MEG effects were found, implying that verbal evaluative conditioning may require conceptual processing and does not engage rapid, possibly sub-cortical, pathways. Results demonstrate the efficacy of verbal evaluative multi-CS conditioning and indicate both common and distinct neural mechanisms of first- and higher-order multi-CS conditioning, thereby informing theories of associative learning. © The Author (2016). Published by Oxford University Press.
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APIS—a novel approach for conditioning honey bees
Kirkerud, Nicholas H.; Wehmann, Henja-Niniane; Galizia, C. Giovanni; Gustav, David
2013-01-01
Honey bees perform robustly in different conditioning paradigms. This makes them excellent candidates for studying mechanisms of learning and memory at both an individual and a population level. Here we introduce a novel method of honey bee conditioning: APIS, the Automatic Performance Index System. In an enclosed walking arena where the interior is covered with an electric grid, presentation of odors from either end can be combined with weak electric shocks to form aversive associations. To quantify behavioral responses, we continuously monitor the movement of the bee by an automatic tracking system. We found that escapes from one side to the other, changes in velocity as well as distance and time spent away from the punished odor are suitable parameters to describe the bee's learning capabilities. Our data show that in a short-term memory test the response rate for the conditioned stimulus (CS) in APIS correlates well with response rate obtained from conventional Proboscis Extension Response (PER)-conditioning. Additionally, we discovered that bees modulate their behavior to aversively learned odors by reducing their rate, speed and magnitude of escapes and that both generalization and extinction seem to be different between appetitive and aversive stimuli. The advantages of this automatic system make it ideal for assessing learning rates in a standardized and convenient way, and its flexibility adds to the toolbox for studying honey bee behavior. PMID:23616753
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APIS-a novel approach for conditioning honey bees.
Kirkerud, Nicholas H; Wehmann, Henja-Niniane; Galizia, C Giovanni; Gustav, David
2013-01-01
Honey bees perform robustly in different conditioning paradigms. This makes them excellent candidates for studying mechanisms of learning and memory at both an individual and a population level. Here we introduce a novel method of honey bee conditioning: APIS, the Automatic Performance Index System. In an enclosed walking arena where the interior is covered with an electric grid, presentation of odors from either end can be combined with weak electric shocks to form aversive associations. To quantify behavioral responses, we continuously monitor the movement of the bee by an automatic tracking system. We found that escapes from one side to the other, changes in velocity as well as distance and time spent away from the punished odor are suitable parameters to describe the bee's learning capabilities. Our data show that in a short-term memory test the response rate for the conditioned stimulus (CS) in APIS correlates well with response rate obtained from conventional Proboscis Extension Response (PER)-conditioning. Additionally, we discovered that bees modulate their behavior to aversively learned odors by reducing their rate, speed and magnitude of escapes and that both generalization and extinction seem to be different between appetitive and aversive stimuli. The advantages of this automatic system make it ideal for assessing learning rates in a standardized and convenient way, and its flexibility adds to the toolbox for studying honey bee behavior.
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Perisse, Emmanuel; Portelli, Geoffrey; Le Goas, Solène; Teste, Elsa; Le Bourg, Eric
2007-11-01
Various learning tasks have been described in Drosophila melanogaster, flies being either tested in groups or at the individual level. Le Bourg and Buecher (Anim Learn Behav 33:330-341, 2002) have designed a task at the individual level: photopositive flies crossing a T-maze learn to prefer the dark exit when the lighted one is associated with the presence of aversive stimuli (humidity and quinine). Previous studies have reported various results (e.g. no effect of age) and the present article further characterizes this task by studying the possible effects of: (1) the intensity of the stimuli (quantity of water or concentration of quinine), (2) various delays between two learning sessions on the learning score at the second session, (3) the rutabaga learning mutation on the learning score. More concentrated quinine solutions increased learning scores but the quantity of water had no effect. Learning scores at the second session were higher with shorter delays between the two learning sessions and retrograde amnesia could decrease this memory score. rutabaga mutants showed learning deficits as in experiments testing groups of flies. This learning task could particularly be used to verify whether learning mutants isolated after experiments testing flies in groups display similar deficits when tested at the individual level.
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Sznycer, Daniel; Lopez Seal, Maria Florencia; Sell, Aaron; Lim, Julian; Porat, Roni; Shalvi, Shaul; Halperin, Eran; Cosmides, Leda; Tooby, John
2017-08-01
Why do people support economic redistribution? Hypotheses include inequity aversion, a moral sense that inequality is intrinsically unfair, and cultural explanations such as exposure to and assimilation of culturally transmitted ideologies. However, humans have been interacting with worse-off and better-off individuals over evolutionary time, and our motivational systems may have been naturally selected to navigate the opportunities and challenges posed by such recurrent interactions. We hypothesize that modern redistribution is perceived as an ancestral scene involving three notional players: the needy other, the better-off other, and the actor herself. We explore how three motivational systems-compassion, self-interest, and envy-guide responses to the needy other and the better-off other, and how they pattern responses to redistribution. Data from the United States, the United Kingdom, India, and Israel support this model. Endorsement of redistribution is independently predicted by dispositional compassion, dispositional envy, and the expectation of personal gain from redistribution. By contrast, a taste for fairness, in the sense of ( i ) universality in the application of laws and standards, or ( ii ) low variance in group-level payoffs, fails to predict attitudes about redistribution.
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Lopez Seal, Maria Florencia; Sell, Aaron; Lim, Julian; Porat, Roni; Halperin, Eran; Cosmides, Leda; Tooby, John
2017-01-01
Why do people support economic redistribution? Hypotheses include inequity aversion, a moral sense that inequality is intrinsically unfair, and cultural explanations such as exposure to and assimilation of culturally transmitted ideologies. However, humans have been interacting with worse-off and better-off individuals over evolutionary time, and our motivational systems may have been naturally selected to navigate the opportunities and challenges posed by such recurrent interactions. We hypothesize that modern redistribution is perceived as an ancestral scene involving three notional players: the needy other, the better-off other, and the actor herself. We explore how three motivational systems—compassion, self-interest, and envy—guide responses to the needy other and the better-off other, and how they pattern responses to redistribution. Data from the United States, the United Kingdom, India, and Israel support this model. Endorsement of redistribution is independently predicted by dispositional compassion, dispositional envy, and the expectation of personal gain from redistribution. By contrast, a taste for fairness, in the sense of (i) universality in the application of laws and standards, or (ii) low variance in group-level payoffs, fails to predict attitudes about redistribution. PMID:28716928
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Effective amino acid composition of seaweeds inducing food preference behaviors in Aplysia kurodai.
Nagahama, Tatsumi; Fujimoto, Kiyo; Takami, Shigemi; Kinugawa, Aiko; Narusuye, Kenji
2009-07-01
Aplysia kurodai feeds on Ulva but rejects Gelidium and Pachydictyon with distinct patterned jaw movements. We previously demonstrated that these movements are induced by taste alone. Thus some chemicals may contribute to induction of these responses. We explored the amino acids composition of Ulva, Gelidium and Pachydictyon extracts used during our taste-induced physiological experiments. These solutions contained many constituents. The concentrations of six amino acids (Asp, Asn, Glu, Gln, Phe, Tau) were obviously different in the three extract solutions. We explored patterned jaw movements following application of solutions containing a pure amino acid. We statistically compared the occurrence numbers of ingestion-like and rejection-like patterned jaw movements (positive and negative values, respectively) for each amino acid. Our results suggested that L-Asn tends to induce ingestion-like responses, likely resulting in a preference of Ulva. In contrast, L-Asp tends to induce rejection-like responses, likely resulting in aversion towards Pachydictyon. In addition, we demonstrated that L-Asn and L-Asp solutions were sufficient to induce muscle activity associated with ingestion-like or rejection-like responses in the jaw muscles of a semi-intact preparation.
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Diet as a factor in behavioral radiation protection following exposure to heavy particles
NASA Technical Reports Server (NTRS)
Rabin, Bernard M.; Shukitt-Hale, Barbara; Joseph, James; Todd, Paul
2005-01-01
Major risks associated with radiation exposures on deep space missions include carcinogenesis due to heavy-particle exposure of cancer-prone tissues and performance decrements due to neurological damage produced by heavy particles. Because exposure to heavy particles can cause oxidative stress, it is possible that antioxidants can be used to mitigate these risks (and possibly some health risks of microgravity). To assess the capacity of antioxidant diets to mitigate the effects of exposure to heavy particles, rats were maintained on antioxidant diets containing 2% blueberry or strawberry extract or a control diet for 8 weeks prior to exposure to 1.5 or 2.0 Gy of accelerated iron particles at Brookhaven National Laboratory. Following irradiation rats were tested on a series of behavioral tasks: amphetamine-induced taste aversion learning, operant responding and spatial learning and memory. The results indicated that the performance of the irradiated rats maintained on the antioxidant diets was, in general, significantly better than that of the control animals, although the effectiveness of the diets ameliorating the radiation-induced deterioration in performance varied as a function of both the specific diet and the specific endpoint. In addition, animals fed antioxidant diets prior to exposure showed reduced heavy particle-induced tumorigenesis one year after exposure compared to the animals fed the control diet. These results suggest that antioxidant diets have the potential to serve as part of a system designed to provide protection to astronauts against the effects of heavy particles on exploratory missions outside the magnetic field of the earth.
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Female babies and risk-aversion: Causal evidence from hospital wards.
Pogrebna, Ganna; Oswald, Andrew J; Haig, David
2018-03-01
Using ultrasound scan data from paediatric hospitals, and the exogenous 'shock' of learning the gender of an unborn baby, the paper documents the first causal evidence that offspring gender affects adult risk-aversion. On a standard Holt-Laury criterion, parents of daughters, whether unborn or recently born, become almost twice as risk-averse as parents of sons. The study demonstrates this in longitudinal and cross-sectional data, for fathers and mothers, for babies in the womb and new-born children, and in a West European nation and East European nation. These findings may eventually aid our understanding of risky health behaviors and gender inequalities. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
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Alterations of male sexual behavior by learned aversions to hamster vaginal secretion.
Johnston, R E; Zahorik, D M; Immler, K; Zakon, H
1978-02-01
Male hamsters poisoned after their first adult exposure to the vaginal secretion of female hamsters became hesitant to approach and ingest the secretion. The same aversion-training procedure also altered the responses of males to estrous females, changing the latency, frequency, and duration of a variety of behaviors that are commonly taken as indexes of sexual attraction or arousal and of copulatory performance. The effects suggest that the aversions to vaginal secretion alter the perceived meaning of the secretion for male hamsters, and analysis of the correlations between various measures of sexual arousal and performance support the hypothesis that separate mechanisms underlie the effects of the secretion on appetitive and consummatory sexual behavior.
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Kolling, Nils; Nelissen, Natalie; Browning, Michael; Rushworth, Matthew F. S.; Harmer, Catherine J.
2017-01-01
To make good decisions, humans need to learn about and integrate different sources of appetitive and aversive information. While serotonin has been linked to value-based decision-making, its role in learning is less clear, with acute manipulations often producing inconsistent results. Here, we show that when the effects of a selective serotonin reuptake inhibitor (SSRI, citalopram) are studied over longer timescales, learning is robustly improved. We measured brain activity with functional magnetic resonance imaging (fMRI) in volunteers as they performed a concurrent appetitive (money) and aversive (effort) learning task. We found that 2 weeks of citalopram enhanced reward and effort learning signals in a widespread network of brain regions, including ventromedial prefrontal and anterior cingulate cortex. At a behavioral level, this was accompanied by more robust reward learning. This suggests that serotonin can modulate the ability to learn via a mechanism that is independent of stimulus valence. Such effects may partly underlie SSRIs’ impact in treating psychological illnesses. Our results highlight both a specific function in learning for serotonin and the importance of studying its role across longer timescales. PMID:28207733
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Taste quality decoding parallels taste sensations.
Crouzet, Sébastien M; Busch, Niko A; Ohla, Kathrin
2015-03-30
In most species, the sense of taste is key in the distinction of potentially nutritious and harmful food constituents and thereby in the acceptance (or rejection) of food. Taste quality is encoded by specialized receptors on the tongue, which detect chemicals corresponding to each of the basic tastes (sweet, salty, sour, bitter, and savory [1]), before taste quality information is transmitted via segregated neuronal fibers [2], distributed coding across neuronal fibers [3], or dynamic firing patterns [4] to the gustatory cortex in the insula. In rodents, both hardwired coding by labeled lines [2] and flexible, learning-dependent representations [5] and broadly tuned neurons [6] seem to coexist. It is currently unknown how, when, and where taste quality representations are established in the cortex and whether these representations are used for perceptual decisions. Here, we show that neuronal response patterns allow to decode which of four tastants (salty, sweet, sour, and bitter) participants tasted in a given trial by using time-resolved multivariate pattern analyses of large-scale electrophysiological brain responses. The onset of this prediction coincided with the earliest taste-evoked responses originating from the insula and opercular cortices, indicating that quality is among the first attributes of a taste represented in the central gustatory system. These response patterns correlated with perceptual decisions of taste quality: tastes that participants discriminated less accurately also evoked less discriminated brain response patterns. The results therefore provide the first evidence for a link between taste-related decision-making and the predictive value of these brain response patterns. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Processing of Intraoral Olfactory and Gustatory Signals in the Gustatory Cortex of Awake Rats
Fontanini, Alfredo
2017-01-01
The integration of gustatory and olfactory information is essential to the perception of flavor. Human neuroimaging experiments have pointed to the gustatory cortex (GC) as one of the areas involved in mediating flavor perception. Although GC's involvement in encoding the chemical identity and hedonic value of taste stimuli is well studied, it is unknown how single GC neurons process olfactory stimuli emanating from the mouth. In this study, we relied on multielectrode recordings to investigate how single GC neurons respond to intraorally delivered tastants and tasteless odorants dissolved in water and whether/how these two modalities converge in the same neurons. We found that GC neurons could either be unimodal, responding exclusively to taste (taste-only) or odor (odor-only), or bimodal, responding to both gustatory and olfactory stimuli. Odor responses were confirmed to result from retronasal olfaction: monitoring respiration revealed that exhalation preceded odor-evoked activity and reversible inactivation of olfactory receptors in the nasal epithelium significantly reduced responses to intraoral odorants but not to tastants. Analysis of bimodal neurons revealed that they encode palatability significantly better than the unimodal taste-only group. Bimodal neurons exhibited similar responses to palatable tastants and odorants dissolved in water. This result suggested that odorized water could be palatable. This interpretation was further supported with a brief access task, where rats avoided consuming aversive taste stimuli and consumed the palatable tastants and dissolved odorants. These results demonstrate the convergence of the chemosensory components of flavor onto single GC neurons and provide evidence for the integration of flavor with palatability coding. SIGNIFICANCE STATEMENT Food perception and choice depend upon the concurrent processing of olfactory and gustatory signals from the mouth. The primary gustatory cortex has been proposed to integrate chemosensory stimuli; however, no study has examined the single-unit responses to intraoral odorant presentation. Here we found that neurons in gustatory cortex can respond either exclusively to tastants, exclusively to odorants, or to both (bimodal). Several differences exist between these groups' responses; notably, bimodal neurons code palatability significantly better than unimodal neurons. This group of neurons might represent a substrate for how odorants gain the quality of tastants. PMID:28077705
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Matters of Taste: Bridging Molecular Physiology and the Humanities
ERIC Educational Resources Information Center
Rangachari, P. K.; Rangachari, Usha
2015-01-01
Taste perception was the focus of an undergraduate course in the health sciences that bridged the sciences and humanities. A problem-based learning approach was used to study the biological issues, whereas the cultural transmutations of these molecular mechanisms were explored using a variety of resources (novels, cookbooks, and films). Multiple…
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On Education and the Taste for Democracy.
ERIC Educational Resources Information Center
Freire, Paulo
1991-01-01
Argues that it is impossible to teach democracy without living democracy. Shows the need to create the taste for democracy, and the appetite for learning, taking risks, and for appreciating differences. Asserts that teachers are not actually champions of civil rights, freedom and democracy but will be called on to fight for these ideals. (PRA)
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Clasen, Matthew M; Hempel, Briana J; Riley, Anthony L
2017-05-01
Although the attenuating effects of drug history on conditioned taste avoidance (CTA) learning have been widely investigated in adults, such effects in adolescents have not been well characterized. Recent research has suggested that the display of the drug pre-exposure effect during adolescence may be drug dependent given that pre-exposure to ethanol attenuates subsequent conditioning, whereas pre-exposure to the classic emetic lithium chloride (LiCl) fails to do so. The present study began investigating the possible drug-dependent nature of the effects of drug pre-exposure by pre-exposing and conditioning adolescent male Sprague-Dawley rats to drugs from two additional classes, specifically psychostimulants (cocaine; Experiment 1) and opioids (morphine; Experiment 2). Consistent with prior work with ethanol (but not LiCl), prior exposure to both cocaine and morphine attenuated taste avoidance induced by these compounds. Although this work supports the view of drug-dependent pre-exposure effects on taste avoidance learning during adolescence, research is needed to assess its mechanisms. © 2017 Wiley Periodicals, Inc.
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Waters, Allison M; Theresiana, Cindy; Neumann, David L; Craske, Michelle G
2017-07-01
This study investigated developmental differences in aversive conditioning, extinction, and reinstatement (i.e., the recovery of conditioned aversive associations following reexposure to the unconditioned stimulus [US] post-extinction). This study examined these mechanisms in children (M age =8.8years), adolescents (M age =16.1years), and adults (M age =32.3years) using differential aversive conditioning with a geometric shape conditional stimulus (CS+) paired with an aversive sound US and another shape (CS-) presented alone. Following an extinction phase in which both CSs were presented alone, half of the participants in each age group received three US exposures (reinstatement condition) and the other half did not (control condition), followed by all participants completing an extinction retest phase on the same day. Findings indicated (a) significant differences in generalizing aversive expectancies to safe stimuli during conditioning and extinction that persisted during retest in children relative to adults and adolescents, (b) significantly less positive CS reevaluations during extinction that persisted during retest in adolescents relative to adults and children, and (c) reinstatement of US expectancies to the CS+ relative to the CS- in all age groups. Results suggest important differences in stimulus safety learning in children and stimulus valence reevaluation in adolescents relative to adults. Copyright © 2017 Elsevier Inc. All rights reserved.
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Wang, Weisheng; Ju, Yun-Yue; Zhou, Qi-Xin; Tang, Jian-Xin; Li, Meng; Zhang, Lei; Kang, Shuo; Chen, Zhong-Guo; Wang, Yu-Jun; Ji, Hui; Ding, Yu-Qiang; Xu, Lin; Liu, Jing-Gen
2017-07-26
Extinction of aversive memories has been a major concern in neuropsychiatric disorders, such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABA A receptor (GABA A R) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization. Active Rac1 is essential and sufficient for GABA A R endocytosis and CPA extinction. Knockdown of Rac1 expression within the vmPFC of rats using Rac1-shRNA suppressed GABA A R endocytosis and CPA extinction, whereas expression of a constitutively active form of Rac1 accelerated GABA A R endocytosis and CPA extinction. The crucial role of GABA A R endocytosis in the LTP induction and CPA extinction is evinced by the findings that blockade of GABA A R endocytosis by a dynamin function-blocking peptide (Myr-P4) abolishes LTP induction and CPA extinction. Thus, the present study provides first evidence that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories and reveals the sequence of molecular events that contribute to learning experience modulation of synaptic GABA A R endocytosis. SIGNIFICANCE STATEMENT This study reveals that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories associated with drug withdrawal and identifies Arc as a downstream effector of Rac1 regulations of synaptic plasticity as well as learning and memory, thereby suggesting therapeutic targets to promote extinction of the unwanted memories. Copyright © 2017 the authors 0270-6474/17/377096-15$15.00/0.
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Conditioned social dominance threat: observation of others' social dominance biases threat learning.
Haaker, Jan; Molapour, Tanaz; Olsson, Andreas
2016-10-01
Social groups are organized along dominance hierarchies, which determine how we respond to threats posed by dominant and subordinate others. The persuasive impact of these dominance threats on mental and physical well-being has been well described but it is unknown how dominance rank of others bias our experience and learning in the first place. We introduce a model of conditioned social dominance threat in humans, where the presence of a dominant other is paired with an aversive event. Participants first learned about the dominance rank of others by observing their dyadic confrontations. During subsequent fear learning, the dominant and subordinate others were equally predictive of an aversive consequence (mild electric shock) to the participant. In three separate experiments, we show that participants' eye-blink startle responses and amygdala reactivity adaptively tracked dominance of others during observation of confrontation. Importantly, during fear learning dominant vs subordinate others elicited stronger and more persistent learned threat responses as measured by physiological arousal and amygdala activity. Our results characterize the neural basis of learning through observing conflicts between others, and how this affects subsequent learning through direct, personal experiences. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
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Conditioned social dominance threat: observation of others’ social dominance biases threat learning
Molapour, Tanaz; Olsson, Andreas
2016-01-01
Social groups are organized along dominance hierarchies, which determine how we respond to threats posed by dominant and subordinate others. The persuasive impact of these dominance threats on mental and physical well-being has been well described but it is unknown how dominance rank of others bias our experience and learning in the first place. We introduce a model of conditioned social dominance threat in humans, where the presence of a dominant other is paired with an aversive event. Participants first learned about the dominance rank of others by observing their dyadic confrontations. During subsequent fear learning, the dominant and subordinate others were equally predictive of an aversive consequence (mild electric shock) to the participant. In three separate experiments, we show that participants’ eye-blink startle responses and amygdala reactivity adaptively tracked dominance of others during observation of confrontation. Importantly, during fear learning dominant vs subordinate others elicited stronger and more persistent learned threat responses as measured by physiological arousal and amygdala activity. Our results characterize the neural basis of learning through observing conflicts between others, and how this affects subsequent learning through direct, personal experiences. PMID:27217107
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An Elegant Mind: Learning and Memory in "Caenorhabditis elegans"
ERIC Educational Resources Information Center
Ardiel, Evan L.; Rankin, Catharine H.
2010-01-01
This article reviews the literature on learning and memory in the soil-dwelling nematode "Caenorhabditis elegans." Paradigms include nonassociative learning, associative learning, and imprinting, as worms have been shown to habituate to mechanical and chemical stimuli, as well as learn the smells, tastes, temperatures, and oxygen levels that…
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Cloutier, Caylen J; Kavaliers, Martin; Ossenkopp, Klaus-Peter
2018-10-01
The multi-variable locomotor activity effects of LiCl treatment in female rats were examined in a conditioned place avoidance/aversion (CPA) paradigm. In addition, the sickness effects of an LPS injection (200 μg/kg), given during adolescents, on CPA learning in adulthood were examined, as were the effects of a homotypic LPS injection (200 μg/kg) just prior to CPA acquisition trials. Female rats were injected with LPS or saline during adolescents (6 weeks of age) and later pretreated with LPS again or saline in an automated two-chamber CPA paradigm with LiCl (95 mg/kg) treatments as the aversive toxin. Results showed that, while adolescent LPS treatment had no long-term effect on the establishment of CPA, it did interfere with the ability of a second LPS challenge in adulthood to impair CPA learning, an effect obtained in subjects pretreated with LPS in the CPA procedure in adulthood only. The results of this study demonstrate the importance of considering the adolescent stage of development when evaluating the effects of environmental challenges on adult behavior. Copyright © 2018 Elsevier B.V. All rights reserved.
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Neural correlates of appetitive-aversive interactions in Pavlovian fear conditioning.
Nasser, Helen M; McNally, Gavan P
2013-03-19
We used Pavlovian counterconditioning in rats to identify the neural mechanisms for appetitive-aversive motivational interactions. In Stage I, rats were trained on conditioned stimulus (CS)-food (unconditioned stimulus [US]) pairings. In Stage II, this appetitive CS was transformed into a fear CS via pairings with footshock. The development of fear responses was retarded in rats that had received Stage I appetitive training. This counterconditioning was associated with increased levels of phosphorylated mitogen activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions, including midline thalamus, rostral agranular insular cortex (RAIC), lateral amygdala, and nucleus accumbens core and shell, but decreased expression in the ventrolateral quadrant of the midbrain periaqueductal gray. These brain regions showing differential pMAPK-IR have previously been identified as part of the fear prediction error circuit. We then examined the causal role of RAIC MAPK in fear learning and showed that Stage II fear learning was prevented by RAIC infusions of the MEK inhibitor PD098059 (0.5 µg/hemisphere). Taken together, these results show that there are opponent interactions between the appetitive and aversive motivational systems during fear learning and that the transformation of a reward CS into a fear CS is linked to heightened activity in the fear prediction error circuit.
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Paret, Christian; Hoesterey, Steffen; Kleindienst, Nikolaus; Schmahl, Christian
2016-10-30
Those with borderline personality disorder (BPD) display altered evaluations regarding reward and punishment compared to others. The processing of rewards is basal for operant conditioning. However, studies addressing operant conditioning in BPD patients are rare. In the current study, an operant conditioning task combining learning acquisition and reversal was used. BPD patients and matched healthy controls (HCs) were exposed to aversive and neutral stimuli to assess the influence of emotion on learning. Picture content, dissociation, aversive tension and symptom severity were rated. Error rates were measured. Results showed no group interactions between aversive versus neutral scenes. The higher emotional arousal, dissociation and tension, the worse the acquisition, but not reversal, scores were for BPD patients. Scores from the Borderline Symptom List were associated with more errors in the reversal, but not the acquisition phase. The results are preliminary evidence for impaired acquisition learning due to increased emotional arousal, dissociation and tension in BPD patients. A failure to process punishment in the reversal phase was associated with symptom severity and may be related to neuropsychological dysfunctioning involving the ventromedial prefrontal cortex. Conclusions are limited due to the correlational study design and the small sample size. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Using signals associated with safety in avoidance learning: computational model of sex differences
Beck, Kevin D.; Pang, Kevin C.H.; Myers, Catherine E.
2015-01-01
Avoidance behavior involves learning responses that prevent upcoming aversive events; these responses typically extinguish when the aversive events stop materializing. Stimuli that signal safety from aversive events can paradoxically inhibit extinction of avoidance behavior. In animals, males and females process safety signals differently. These differences help explain why women are more likely to be diagnosed with an anxiety disorder and exhibit differences in symptom presentation and course compared to men. In the current study, we extend an existing model of strain differences in avoidance behavior to simulate sex differences in rats. The model successfully replicates data showing that the omission of a signal associated with a period of safety can facilitate extinction in females, but not males, and makes novel predictions that this effect should depend on the duration of the period, the duration of the signal itself, and its occurrence within that period. Non-reinforced responses during the safe period were also found to be important in the expression of these patterns. The model also allowed us to explore underlying mechanisms for the observed sex effects, such as whether safety signals serve as occasion setters for aversive events, to determine why removing them can facilitate extinction of avoidance. The simulation results argue against this account, and instead suggest the signal may serve as a conditioned reinforcer of avoidance behavior. PMID:26213650
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[Extinction and Reconsolidation of Memory].
Zuzina, A B; Balaban, P M
2015-01-01
Retrieval of memory followed by reconsolidation can strengthen a memory, while retrieval followed by extinction results in a decrease of memory performance due to weakening of existing memory or formation of a competing memory. In our study we analyzed the behavior and responses of identified neurons involved in the network underlying aversive learning in terrestrial snail Helix, and made an attempt to describe the conditions in which the retrieval of memory leads either to extinction or reconsolidation. In the network underlying the withdrawal behavior, sensory neurons, premotor interneurons, motor neurons, and modulatory for this network serotonergic neurons are identified and recordings from representatives of these groups were made before and after aversive learning. In the network underlying feeding behavior, the premotor modulatory serotonergic interneurons and motor neurons involved in motor program of feeding are identified. Analysis of changes in neural activity after aversive learning showed that modulatory neurons of feeding behavior do not demonstrate any changes (sometimes a decrease of responses to food was observed), while responses to food in withdrawal behavior premotor interneurons changed qualitatively, from under threshold EPSPs to spike discharges. Using a specific for serotonergic neurons neurotoxin 5,7-DiHT it was shown previously that the serotonergic system is necessary for the aversive learning, but is not necessary for maintenance and retrieval of this memory. These results suggest that the serotonergic neurons that are necessary as part of a reinforcement for developing the associative changes in the network may be not necessary for the retrieval of memory. The hypothesis presented in this review concerns the activity of the "reinforcement" serotonergic neurons that is suggested to be the gate condition for the choice between extinction/reconsolidation triggered by memory retrieval: if these serotonergic neurons do not respond during the retrieval due to adaptation, habituation, changes in environment, etc., then we will observe the extinction; while if these neurons respond to the CS during memory retrieval, we will observe the reconsolidation phenomenon.