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Sample records for stria terminalis induces

  1. Ethanol-induced anxiolysis and neuronal activation in the amygdala and bed nucleus of the stria terminalis

    PubMed Central

    Sharko, Amanda C.; Kaigler, Kris F.; Fadel, Jim R.; Wilson, Marlene A.

    2016-01-01

    High rates of comorbidity for anxiety and alcohol-use disorders suggest a causal relationship between these conditions. Previous work demonstrates basal anxiety levels in outbred Long-Evans rats correlate with differences in voluntary ethanol consumption and that amygdalar Neuropeptide Y (NPY) systems may play a role in this relationship. The present work explores the possibility that differences in sensitivity to ethanol’s anxiolytic effects contribute to differential ethanol self-administration in these animals and examines the potential role of central and peripheral NPY in mediating this relationship. Animals were first exposed to the elevated plus maze (EPM) to assess individual differences in anxiety-like behaviors and levels of circulating NPY and corticosterone (CORT). Rats were then tested for anxiety-like behavior in the light-dark box (LD box) following acute ethanol treatment (1 g/kg; intraperitoneally [i.p.]), and neuronal activation in the amygdala and bed nucleus of the stria terminalis (BNST) was assessed using Fos immunohistochemistry. EPM exposure increased plasma CORT levels without altering plasma NPY levels. Acute ethanol treatment significantly increased light-dark transitions and latency to re-enter the light arena, but no differences were seen between high- and low-anxiety groups and no correlations were found between anxiety-like behaviors in the EPM and LD box. Acute ethanol treatment significantly increased Fos immunoreactivity in the BNST and the central amygdala. Although NPY neurons were not significantly activated following ethanol exposure, in saline-treated animals lower levels of anxiety-like behavior in the LD box (more time in the light arena and more transitions) were correlated with higher NPY-positive cell density in the central amygdala. Our results suggest that activation of the CeA and BNST are involved in the behavioral expression of ethanol-induced anxiolysis, and that differences in basal anxiety state may be

  2. Ethanol-induced anxiolysis and neuronal activation in the amygdala and bed nucleus of the stria terminalis.

    PubMed

    Sharko, Amanda C; Kaigler, Kris F; Fadel, Jim R; Wilson, Marlene A

    2016-02-01

    High rates of comorbidity for anxiety and alcohol-use disorders suggest a causal relationship between these conditions. Previous work demonstrates basal anxiety levels in outbred Long-Evans rats correlate with differences in voluntary ethanol consumption and that amygdalar Neuropeptide Y (NPY) systems may play a role in this relationship. The present work explores the possibility that differences in sensitivity to ethanol's anxiolytic effects contribute to differential ethanol self-administration in these animals and examines the potential role of central and peripheral NPY in mediating this relationship. Animals were first exposed to the elevated plus maze (EPM) to assess individual differences in anxiety-like behaviors and levels of circulating NPY and corticosterone (CORT). Rats were then tested for anxiety-like behavior in the light-dark box (LD box) following acute ethanol treatment (1 g/kg; intraperitoneally [i.p.]), and neuronal activation in the amygdala and bed nucleus of the stria terminalis (BNST) was assessed using Fos immunohistochemistry. EPM exposure increased plasma CORT levels without altering plasma NPY levels. Acute ethanol treatment significantly increased light-dark transitions and latency to re-enter the light arena, but no differences were seen between high- and low-anxiety groups and no correlations were found between anxiety-like behaviors in the EPM and LD box. Acute ethanol treatment significantly increased Fos immunoreactivity in the BNST and the central amygdala. Although NPY neurons were not significantly activated following ethanol exposure, in saline-treated animals lower levels of anxiety-like behavior in the LD box (more time in the light arena and more transitions) were correlated with higher NPY-positive cell density in the central amygdala. Our results suggest that activation of the CeA and BNST are involved in the behavioral expression of ethanol-induced anxiolysis, and that differences in basal anxiety state may be correlated

  3. How does pain induce negative emotion? Role of the bed nucleus of the stria terminalis in pain-induced place aversion.

    PubMed

    Minami, M; Ide, S

    2015-01-01

    Pain consists of sensory-discriminative and negative-affective components. Neuronal mechanisms for the sensory component of pain have been investigated extensively. On the other hand, neuronal mechanisms for the affective component of pain remain to be investigated. Recent behavioral studies have revealed the brain regions and neuronal mechanisms involved in the affective component of pain. Glutamatergic transmission within the anterior cingulate cortex and basolateral amygdaloid nucleus plays a critical role in pain-induced aversion. Noradrenaline and corticotropin-releasing factor (CRF) within the ventral and dorsolateral parts of the bed nucleus of the stria terminalis (BNST), respectively, play important roles in paininduced aversion. Electrophysiological studies have revealed that both noradrenaline and CRF activate type II BNST neurons, which may inhibit the BNST output neurons. A recent histochemical study showed that most VTA-projecting BNST output neurons are GABAergic neurons, which preferentially make synaptic contact with VTA GABAergic neurons. Therefore, activation of VTA-projecting BNST output neurons should increase the neuronal excitability of VTA dopaminergic (DAergic) neurons through increased inhibitory input to VTA GABAergic neurons, which negatively regulate VTA DAergic neurons. Pain-induced release of noradrenaline and CRF within the BNST may activate type II BNST neurons, which could suppress VTA-projecting BNST output neurons, thereby attenuating the excitatory influence to the VTA DAergic neurons. Recent optogenetic studies suggest that the suppression of VTA DAergic neurons is sufficient to induce place aversion. Pain-induced place aversion may be due to the suppression of VTA DAergic neurons via the processing of nociceptive information within the BNST.

  4. Temporary inactivation of the anterior part of the bed nucleus of the stria terminalis blocks alarm pheromone-induced defensive behavior in rats

    PubMed Central

    Breitfeld, Tino; Bruning, Johann E. A.; Inagaki, Hideaki; Takeuchi, Yukari; Kiyokawa, Yasushi; Fendt, Markus

    2015-01-01

    Rats emit an alarm pheromone in threatening situations. Exposure of rats to this alarm pheromone induces defensive behaviors, such as head out behavior, and increases c-Fos expression in brain areas involved in the mediation of defensive behaviors. One of these brain areas is the anterior bed nucleus of the stria terminalis (aBNST). The goal of the present study was to investigate if pharmacological inactivation of the aBNST by local microinjections of the GABAA receptor-agonist muscimol modulates alarm pheromone-induced defensive behaviors. We first established the behavioral paradigm of alarm pheromone-induced defensive behaviors in Sprague-Dawley rats in our laboratory. In a second experiment, we inactivated the aBNST, then exposed rats to one of four different odors (neck odor, female urine, alarm pheromone, fox urine) and tested the effects of the aBNST inactivation on the behavior in response to these odors. Our data show that temporary inactivation of the aBNST blocked head out behavior in response to the alarm pheromone. This indicates that the aBNST plays an important role in the mediation of the alarm pheromone-induced defensive behavior in rats. PMID:26441496

  5. Effect of sex differences and gonadal hormones on kainic acid-induced neurodegeneration in the bed nucleus of the stria terminalis of the rat.

    PubMed

    Pereno, German Leandro; Balaszczuk, Verónica; Beltramino, Carlos Alberto

    2012-05-01

    Previously we have demonstrated that medial nucleus of the amygdala, which is part of medial extended amygdala, is damaged by status epilepticus induced by kainic acid (KA) and this neurodegeneration was prevents by estrogen replacement. The medial bed nucleus of stria terminalis (BSTM) also belong to medial extended amygdala and it is uncertain whether the gonadal hormones are protective or not against this neurotoxicity in the BSTM. Here we show that a single i.p. injection of KA (9 mg/kg) induces neurodegeneration in the subnuclei of the BSTM of rats with different degrees of intensity in males and females. A differential neuroprotective effect of the gonadal hormones was also observed. In diestrous rats, massive neuronal death similar to that in the ovariectomized females was detected. BSTM neurons of proestrous rats, like the ovariectomized treated with estrogen, were significantly less affected by the KA. Testosterone produced a mild neuroprotective action, but dihydrotestosterone did not protect. A similar pattern was observed in all male groups. This results show that estrogen protects BSTM neurons from KA neurotoxicity and androgens are partially neuroprotective; and probably this effect of androgens is due to conversion to estrogen.

  6. Suckling induces a daily rhythm in the preoptic area and lateral septum but not in the bed nucleus of the stria terminalis in lactating rabbit does

    PubMed Central

    Meza, Enrique; Aguirre, Juan; Waliszewski, Stefan; Caba, Mario

    2014-01-01

    Maternal behavior in the rabbit is restricted to a brief nursing period every day. Previously we demonstrated that this event induces daily rhythms of PER1 protein, the product of the clock gene Per1, in oxytocinergic and dopaminergic populations in the hypothalamus of lactating rabbit does. This is significant for the periodic production and ejection of milk, but the activation of other areas of the brain has not been explored. Here we hypothesized that daily suckling will induce a rhythm in the preoptic area, lateral septum and bed nucleus of the stria terminalis, which are important areas for the expression of maternal behavior in mammals including the rabbit. To this end, we analyzed PER1 expression in those areas through a complete 24-h cycle at lactation day 7. Does were scheduled to nurse during either the day at 10:00 (ZT03) or the night at 02:00 (ZT19) h. Non-pregnant, non-lactating females were used as controls. In contrast to control females, lactating does show a clear, significant rhythm of PER1 that shifts in parallel to timing of nursing in the preoptic area and lateral septum. We determined that the maximal expression of PER1 at 8 h after scheduled nursing decreased significantly at 24 and 48 h after the absence of suckling. This effect was more pronounced in the lateral septum than in the preoptic area. We conclude that daily suckling is a powerful stimulus that induces rhythmic activity in brain structures in the rabbit that appear to be part of a maternal entrainable circuit. PMID:25370159

  7. Suckling induces a daily rhythm in the preoptic area and lateral septum but not in the bed nucleus of the stria terminalis in lactating rabbit does.

    PubMed

    Meza, Enrique; Aguirre, Juan; Waliszewski, Stefan; Caba, Mario

    2015-01-01

    Maternal behavior in the rabbit is restricted to a brief nursing period every day. Previously, we demonstrated that this event induces daily rhythms of Period1 (PER1) protein, the product of the clock gene Per1, in oxytocinergic and dopaminergic populations in the hypothalamus of lactating rabbit does. This is significant for the periodic production and ejection of milk, but the activation of other areas of the brain has not been explored. Here, we hypothesised that daily suckling would induce a rhythm in the preoptic area, lateral septum, and bed nucleus of the stria terminalis, which are important areas for the expression of maternal behavior in mammals, including the rabbit. To this end, we analysed PER1 expression in those areas through a complete 24-h cycle at lactation day 7. Does were scheduled to nurse during either the day at 10:00 h [zeitgeber time (ZT)03] or the night at 02:00 h (ZT19). Non-pregnant, non-lactating females were used as controls. In contrast to control females, lactating does showed a clear, significant rhythm of PER1 that shifted in parallel with the timing of nursing in the preoptic area and lateral septum. We determined that the maximal expression of PER1 at 8 h after scheduled nursing decreased significantly at 24 and 48 h after the absence of suckling. This effect was more pronounced in the lateral septum than in the preoptic area. We conclude that daily suckling is a powerful stimulus inducing rhythmic activity in brain structures in the rabbit that appear to form part of a maternal entrainable circuit.

  8. Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

    PubMed Central

    Greenberg, Gian D.; Laman-Maharg, Abigail; Campi, Katharine L.; Voigt, Heather; Orr, Veronica N.; Schaal, Leslie; Trainor, Brian C.

    2014-01-01

    Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females. PMID:24409132

  9. Stress-induced alterations in anxiety-like behavior and adaptations in plasticity in the bed nucleus of the stria terminalis.

    PubMed

    Conrad, Kelly L; Louderback, Katherine M; Gessner, Caitlin P; Winder, Danny G

    2011-08-03

    In vulnerable individuals, exposure to stressors can result in chronic disorders such as generalized anxiety disorder (GAD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). The extended amygdala is critically implicated in mediating acute and chronic stress responsivity and anxiety-like behaviors. The bed nucleus of the stria terminalis (BNST), a subregion of the extended amygdala, serves as a relay of corticolimbic information to the paraventricular nucleus of the hypothalamus (PVN) to directly influence the stress response. To investigate the influence of the corticosteroid milieu and housing conditions on BNST function, adult C57Bl/6J were either acutely or chronically administered corticosterone (CORT, 25mg/kg in sesame oil) or vehicle (sesame oil) or were group housed or socially isolated for 1 day (acute) or 6-8 weeks (chronic). To ascertain whether these stressors could influence anxiety-like behavior, studies were performed using the novel open-field (NOF) and the elevated zero maze (EZM) tests. To investigate potential associated changes in plasticity, alterations in BNST function were assessed using ex vivo extracellular field potential recordings in the (dorsal-lateral) dlBNST and a high frequency stimulus protocol to induce long-term potentiation (LTP). Our results suggest that chronic CORT injections and chronic social isolation housing conditions lead to an increase in anxiety-like behavior on the EZM and NOF. Chronically stressed mice also displayed a parallel blunting of LTP in the dlBNST. Conversely, acute social isolation housing had no effect on anxiety-like behavior but still resulted in a blunting of LTP in the dlBNST. Collectively, our results suggest acute and chronic stressors can have a distinct profile on plasticity in the BNST that is not uniformly associated with an increase in anxiety-like behavior.

  10. Tissue plasminogen activator in the bed nucleus of stria terminalis regulates acoustic startle.

    PubMed

    Matys, T; Pawlak, R; Strickland, S

    2005-01-01

    The bed nucleus of stria terminalis is a basal forebrain region involved in regulation of hormonal and behavioral responses to stress. In this report we demonstrate that bed nucleus of stria terminalis has a high and localized expression of tissue plasminogen activator, a serine protease with neuromodulatory properties and implicated in neuronal plasticity. Tissue plasminogen activator activity in the bed nucleus of stria terminalis is transiently increased in response to acute restraint stress or i.c.v. administration of a major stress mediator, corticotropin-releasing factor. We show that tissue plasminogen activator is important in bed nucleus of stria terminalis function using two criteria: 1, Neuronal activation in this region as measured by c-fos induction is reduced in tissue plasminogen activator-deficient mice; and 2, a bed nucleus of stria terminalis-dependent behavior, potentiation of acoustic startle by corticotropin-releasing factor, is attenuated in tissue plasminogen activator-deficient mice. These studies identify a novel site of tissue plasminogen activator expression in the mouse brain and demonstrate a functional role for this protease in the bed nucleus of stria terminalis.

  11. Functional Heterogeneity in the Bed Nucleus of the Stria Terminalis

    PubMed Central

    Gungor, Nur Zeynep

    2016-01-01

    Early work stressed the differing involvement of the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) in the genesis of fear versus anxiety, respectively. In 2009, Walker, Miles, and Davis proposed a model of amygdala-BNST interactions to explain these functional differences. This model became extremely influential and now guides a new wave of studies on the role of BNST in humans. Here, we consider evidence for and against this model, in the process highlighting central principles of BNST organization. This analysis leads us to conclude that BNST's influence is not limited to the generation of anxiety-like responses to diffuse threats, but that it also shapes the impact of discrete threatening stimuli. It is likely that BNST-CeA interactions are involved in modulating responses to such threats. In addition, whereas current views emphasize the contributions of the anterolateral BNST region in anxiety, accumulating data indicate that the anteromedial and anteroventral regions also play a critical role. The presence of multiple functional subregions within the small volume of BNST raises significant technical obstacles for functional imaging studies in humans. PMID:27488624

  12. Neuronal Correlates of Fear Conditioning in the Bed Nucleus of the Stria Terminalis

    ERIC Educational Resources Information Center

    Haufler, Darrell; Nagy, Frank Z.; Pare, Denis

    2013-01-01

    Lesion and inactivation studies indicate that the central amygdala (CeA) participates in the expression of cued and contextual fear, whereas the bed nucleus of the stria terminalis (BNST) is only involved in the latter. The basis for this functional dissociation is unclear because CeA and BNST form similar connections with the amygdala and…

  13. Extracellular-signal regulated kinase 1-dependent metabotropic glutamate receptor 5-induced long-term depression in the bed nucleus of the stria terminalis is disrupted by cocaine administration.

    PubMed

    Grueter, Brad A; Gosnell, Heather B; Olsen, Christopher M; Schramm-Sapyta, Nicole L; Nekrasova, Tanya; Landreth, Gary E; Winder, Danny G

    2006-03-22

    The bed nucleus of the stria terminalis (BNST) is a key component of the CNS stress and reward circuit. Synaptic plasticity in this region could in part underlie the persistent behavioral alterations in generalized anxiety and addiction. Group I metabotropic glutamate receptors (mGluRs) have been implicated in stress, addiction, and synaptic plasticity, but their roles in the BNST are unknown. We find that activation of group I mGluRs in the dorsal BNST induces depression of excitatory synaptic transmission through two distinct mechanisms. First, a combined activation of group I mGluRs (mGluR1 and mGluR5) induces a transient depression that is cannabinoid 1 receptor dependent. Second, as with endocannabinoid-independent group I mGluR long-term depression (LTD) in the adult hippocampus, we find that activation of mGluR5 induces an extracellular signal-regulated kinase (ERK)-dependent LTD. Surprisingly, our data demonstrate that this LTD requires the ERK1 rather than ERK2 isoform, establishing a key role for this isoform in the CNS. Finally, we find that this LTD is dramatically reduced after multiple exposures but not a single exposure to cocaine, suggesting a role for this form of plasticity in the actions of psychostimulants on anxiety and reward circuitries and their emergent control of animal behavior.

  14. Role of Bed Nucleus of the Stria Terminalis Corticotrophin-Releasing Factor Receptors in Frustration Stress-Induced Binge-Like Palatable Food Consumption in Female Rats with a History of Food Restriction

    PubMed Central

    Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele; Bossert, Jennifer M.; Rice, Kenner C.; Ubaldi, Massimo; St. Laurent, Robyn; Gaetani, Silvana; Massi, Maurizio; Shaham, Yavin

    2014-01-01

    We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This “frustration stress” manipulation also activates the hypothalamic–pituitary–adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10–20 mg/kg) and BNST (25–50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist d-Phe-CRF(12–41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders. PMID:25143612

  15. Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction.

    PubMed

    Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele; Bossert, Jennifer M; Rice, Kenner C; Ubaldi, Massimo; St Laurent, Robyn; Gaetani, Silvana; Massi, Maurizio; Shaham, Yavin; Cifani, Carlo

    2014-08-20

    We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10-20 mg/kg) and BNST (25-50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist D-Phe-CRF(12-41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders.

  16. Adolescent nicotine alters dendritic morphology in the bed nucleus of the stria terminalis.

    PubMed

    Smith, Kelsey C; Ehlinger, Daniel G; Smith, Robert F

    2015-03-17

    Adolescent nicotine increases dendritic elaboration in several areas associated with the extended amygdala. It also increases anxiety-like behavior in adulthood. An unresolved question is whether adolescent nicotine alters dendritic structure in the bed nucleus of the stria terminalis (BNST), which may contribute to altered anxiety-like behavior. To investigate this possibility, adolescent male Sprague-Dawley rats were administered nicotine (0.5mg/kg/day) 3 days a week for 2 consecutive weeks, starting at postnatal day P (32). 17 days following the end of dosing, brains were processed for Golgi-Cox staining, and neurons were digitally reconstructed in three dimensions. Animals previously treated with nicotine exhibited an increase in the total number of branches and total length of dendrites on BNST neurons. Sholl analysis revealed an increase in the number of intersections with concentric spheres, increased amount of dendritic material within concentric spheres, and an increase of dendritic branching within concentric spheres occurring between 20 and 300 μm from the soma in dendrites. Collectively, our results show that adolescent nicotine alters dendritic structure (by triggering new branch growth), and, by inference, connectivity of the BNST, which may contribute to alterations in behavior induced by adolescent nicotine.

  17. The Bed Nucleus of the Stria Terminalis Regulates Ethanol-Seeking Behavior in Mice

    PubMed Central

    Pina, Melanie M.; Young, Emily A.; Ryabinin, Andrey E.; Cunningham, Christopher L.

    2015-01-01

    Drug-associated stimuli are considered important factors in relapse to drug use. In the absence of drug, these cues can trigger drug craving and drive subsequent drug seeking. One structure that has been implicated in this process is the bed nucleus of the stria terminalis (BNST), a chief component of the extended amygdala. Previous studies have established a role for the BNST in cue-induced cocaine seeking. However, it is unclear if the BNST underlies cue-induced seeking of other abused drugs such as ethanol. In the present set of experiments, BNST involvement in ethanol-seeking behavior was assessed in male DBA/2J mice using the conditioned place preference procedure (CPP). The BNST was inhibited during CPP expression using electrolytic lesions (Experiment 1), co-infusion of GABAA and GABAB receptor agonists muscimol and baclofen (M+B; Experiment 2), and activation of inhibitory designer receptors exclusively activated by designer drugs (hM4Di-DREADD) with clozapine-N-oxide (CNO; Experiment 3). The magnitude of ethanol CPP was reduced significantly by each of these techniques. Notably, infusion of M+B (Exp. 2) abolished CPP altogether. Follow-up studies to Exp. 3 showed that ethanol cue-induced c-Fos immunoreactivity in the BNST was reduced by hM4Di activation (Experiment 4) and in the absence of hM4Di, CNO did not affect ethanol CPP (Experiment 5). Combined, these findings demonstrate that the BNST is involved in the modulation of cue-induced ethanol-seeking behavior. PMID:26302652

  18. The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in mice.

    PubMed

    Pina, Melanie M; Young, Emily A; Ryabinin, Andrey E; Cunningham, Christopher L

    2015-12-01

    Drug-associated stimuli are considered important factors in relapse to drug use. In the absence of drug, these cues can trigger drug craving and drive subsequent drug seeking. One structure that has been implicated in this process is the bed nucleus of the stria terminalis (BNST), a chief component of the extended amygdala. Previous studies have established a role for the BNST in cue-induced cocaine seeking. However, it is unclear if the BNST underlies cue-induced seeking of other abused drugs such as ethanol. In the present set of experiments, BNST involvement in ethanol-seeking behavior was assessed in male DBA/2J mice using the conditioned place preference procedure (CPP). The BNST was inhibited during CPP expression using electrolytic lesions (Experiment 1), co-infusion of GABAA and GABAB receptor agonists muscimol and baclofen (M+B; Experiment 2), and activation of inhibitory designer receptors exclusively activated by designer drugs (hM4Di-DREADD) with clozapine-N-oxide (CNO; Experiment 3). The magnitude of ethanol CPP was reduced significantly by each of these techniques. Notably, infusion of M+B (Exp. 2) abolished CPP altogether. Follow-up studies to Exp. 3 showed that ethanol cue-induced c-Fos immunoreactivity in the BNST was reduced by hM4Di activation (Experiment 4) and in the absence of hM4Di, CNO did not affect ethanol CPP (Experiment 5). Combined, these findings demonstrate that the BNST is involved in the modulation of cue-induced ethanol-seeking behavior.

  19. Ethanol induced adaptations in 5-HT2c receptor signaling in the bed nucleus of stria terminalis: Implications for anxiety during ethanol withdrawal

    PubMed Central

    Marcinkiewcz, Catherine A.; Dorrier, Cayce E.; Lopez, Alberto J.; Kash, Thomas L.

    2015-01-01

    One of the hallmarks of alcohol dependence is the presence of a withdrawal syndrome during abstinence, which manifests as physical craving for alcohol accompanied by subjective feelings of anxiety. Using a model of chronic intermittent ethanol (CIE) vapor in mice, we investigated the role of serotonin2c signaling in the BNST as a neural substrate underlying ethanol-induced anxiety during withdrawal. Mice were subjected to a 5-day CIE regimen of 16 hours of ethanol vapor exposure followed by an 8 hour “withdrawal” period between exposures. After the 5th and final exposure, mice were withdrawn for 24 hours or 1 week before experiments began. Anxiety-like behavior was assessed in the social approach, light dark, and open field test with mice showing deficits in social, but not general anxiety-like behavior that was alleviated by pretreatment with the 5HT2c-R antagonist SB 242,084 (3 mg/kg, i.p.) 24 hours and 1 week post-CIE. Using immunohistochemistry and whole cell patch clamp electrophysiology, we also found that CIE increased FOS-IR and enhanced neuronal excitability in the ventral BNST (vBNST) 24 hrs into withdrawal in a 5HT2c-R dependent manner. This enhanced excitability persisted for 1 week post-CIE. We also found that mCPP, a 5HT2c/b agonist, induced a more robust depolarization in cells of the vBNST in CIE mice, confirming that 5HT2c-R signaling is upregulated in the vBNST following CIE. Taken together, these results suggest that CIE upregulates 5HT2c-R signaling in the vBNST, leading to increased excitability. This enhanced excitability of the vBNST may drive increased anxiety-like behavior during ethanol withdrawal. PMID:25229718

  20. ASIC1A in the bed nucleus of the stria terminalis mediates TMT-evoked freezing

    PubMed Central

    Taugher, Rebecca J.; Ghobbeh, Ali; Sowers, Levi P.; Fan, Rong; Wemmie, John A.

    2015-01-01

    Mice display an unconditioned freezing response to TMT, a predator odor isolated from fox feces. Here we found that in addition to freezing, TMT caused mice to decrease breathing rate, perhaps because of the aversive smell. Consistent with this possibility, olfactory bulb lesions attenuated this effect of TMT, as well as freezing. Interestingly, butyric acid, another foul odor, also caused mice to reduce breathing rate. However, unlike TMT, butyric acid did not induce freezing. Thus, although these aversive odors may affect breathing, the unpleasant smell and suppression of breathing by themselves are insufficient to cause freezing. Because the acid-sensing ion channel-1A (ASIC1A) has been previously implicated in TMT-evoked freezing, we tested whether Asic1a disruption also altered breathing. We found that TMT reduced breathing rate in both Asic1a+/+ and Asic1a−/− mice, suggesting that ASIC1A is not required for TMT to inhibit breathing and that the absence of TMT-evoked freezing in the Asic1a−/− mice is not due to an inability to detect TMT. These observations further indicate that ASIC1A must affect TMT freezing in another way. Because the bed nucleus of the stria terminalis (BNST) has been critically implicated in TMT-evoked freezing and robustly expresses ASIC1A, we tested whether ASIC1A in the BNST plays a role in TMT-evoked freezing. We disrupted ASIC1A in the BNST of Asic1aloxP/loxP mice by delivering Cre recombinase to the BNST with an adeno-associated virus (AAV) vector. We found that disrupting ASIC1A in the BNST reduced TMT-evoked freezing relative to control mice in which a virus expressing eGFP was injected. To test whether ASIC1A in the BNST was sufficient to increase TMT-evoked freezing, we used another AAV vector to express ASIC1A in the BNST of Asic1a−/− mice. We found region-restricted expression of ASIC1A in the BNST increased TMT-elicited freezing. Together, these data suggest that the BNST is a key site of ASIC1A action in TMT

  1. Desipramine and citalopram attenuate pretest swim-induced increases in prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis and the lateral division of the central nucleus of the amygdala in the forced swimming test.

    PubMed

    Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Cho, Jin Hee; Cho, Yun Ha; Kim, Dong-Hoon; Shin, Kyung Ho

    2014-10-01

    Dynorphin in the nucleus accumbens shell plays an important role in antidepressant-like effect in the forced swimming test (FST), but it is unclear whether desipramine and citalopram treatments alter prodynorphin levels in other brain areas. To explore this possibility, we injected mice with desipramine and citalopram 0.5, 19, and 23 h after a 15-min pretest swim and observed changes in prodynorphin expression before the test swim, which was conducted 24 h after the pretest swim. The pretest swim increased prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis (dBNST) and lateral division of the central nucleus of the amygdala (CeL). This increase in prodynorphin immunoreactivity in the dBNST and CeL was blocked by desipramine and citalopram treatments. Similar changes in prodynorphin mRNA levels were observed in the dBNST and CeL, but these changes did not reach significance. To understand the underlying mechanism, we assessed changes in phosphorylated CREB at Ser(133) (pCREB) immunoreactivity in the dBNST and central nucleus of the amygdala (CeA). Treatment with citalopram but not desipramine after the pretest swim significantly increased pCREB immunoreactivity only in the dBNST. These results suggest that regulation of prodynorphin in the dBNST and CeL before the test swim may be involved in the antidepressant-like effect of desipramine and citalopram in the FST and suggest that changes in pCREB immunoreactivity in these areas may not play an important role in the regulation of prodynorphin in the dBNST and CeA.

  2. Resting State Connectivity of the Bed Nucleus of the Stria Terminalis at Ultra-high Field

    PubMed Central

    Torrisi, Salvatore; O'Connell, Katherine; Davis, Andrew; Reynolds, Richard; Balderston, Nick; Fudge, Julie; Grillon, Christian; Ernst, Monique

    2015-01-01

    The bed nucleus of the stria terminalis (BNST), a portion of the ‘extended amygdala’, is implicated in the pathophysiology of anxiety and addiction disorders. Its small size and connection to other small regions prevents standard imaging techniques from easily capturing it and its connectivity with confidence. Seed-based resting state functional connectivity is an established method for mapping functional connections across the brain from a region of interest. We therefore mapped the BNST resting state network with high spatial resolution using 7 Tesla fMRI, demonstrating the in vivo reproduction of many human BNST connections previously described only in animal research. We identify strong BNST functional connectivity in amygdala, hippocampus and thalamic subregions, caudate, periaqueductal gray, hypothalamus and cortical areas such as the medial PFC and precuneus. This work, which demonstrates the power of ultra-high field for mapping functional connections in the human, is an important step towards elucidating cortical and subcortical regions and subregions of the BNST network. PMID:26178381

  3. Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis

    PubMed Central

    Daniel, Sarah E; Rainnie, Donald G

    2016-01-01

    The anterior bed nucleus of the stria terminalis (BNST) has been recognized as a critical structure in regulating trait anxiety, contextual fear memory, and appetitive behavior, and is known to be sensitive to stress manipulations. As one of the most complex structures in the central nervous system, the intrinsic circuitry of the BNST is largely unknown; however, recent technological developments have allowed researchers to begin to untangle the internal connections of the nucleus. This research has revealed the possibility of two opposing circuits, one anxiolytic and one anxiogenic, within the BNST, the relative strength of which determines the behavioral outcome. The balance of these pathways is critical in maintaining a normal physiological and behavioral state; however, stress and drugs of abuse can differentially affect the opposing circuitry within the nucleus to shift the balance to a pathological state. In this review, we will examine how stress interacts with the neuromodulators, corticotropin-releasing factor, norepinephrine, dopamine, and serotonin to affect the circuitry of the BNST as well as how synaptic plasticity in the BNST is modulated by stress, resulting in long-lasting changes in the circuit and behavioral state. PMID:26096838

  4. The bed nucleus of the stria terminalis modulates learning after stress in masculinized but not cycling females.

    PubMed

    Bangasser, Debbie A; Shors, Tracey J

    2008-06-18

    Exposure to an acute stressful event enhances classical eyeblink conditioning in male rats, but severely impairs conditioning in female rats. Previous studies have demonstrated that the hippocampus and amygdala critically mediate this effect in both sexes. Thus, although stress affects learning in opposite ways, the structures involved are similar. Previously, we found that the bed nucleus of the stria terminalis (BNST) is also necessary for the enhanced learning after stress in male rats. Here we used BNST inactivation to determine whether the BNST, a sexually dimorphic brain region, is required in female rats for the impaired learning after stress. Interestingly, inactivation of the BNST did not prevent the stress-induced impairment of conditioning in females. Thus, unlike the hippocampus and amygdala, the BNST is critically involved in the modulation of learning by stress in males, but not in females. This exclusive involvement in males may be caused by the sex differences within the BNST. These sex differences result from early testosterone exposure, which masculinizes brain regions including the BNST. Previously, we reported that, like males, females with brains that are masculinized at birth learn better after stressful experience. Here we found that the enhanced learning after stress in masculinized females was prevented by BNST inactivation, just like in males. These data suggest that a masculinized BNST is required for the enhanced learning after a stressful experience. Importantly, together these studies indicate that males and females can engage different brain structures to modulate learning after a stressful experience.

  5. Neurogenetic and morphogenetic heterogeneity in the bed nucleus of the stria terminalis

    SciTech Connect

    Bayer, S.A.

    1987-11-01

    Neurogenesis and morphogenesis in the rat bed nucleus of the stria terminalis (strial bed nucleus) were examined with (/sup 3/H)thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of (/sup 3/H)thymidine on 2 consecutive gestational days. Nine groups of embryos were exposed to (/sup 3/H)thymidine on E13-E14, E14-E15,... E21-E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24-hour periods were quantified at six anteroposterior levels in the strial bed nucleus. On the basis of neurogenetic gradients, the strial bed nucleus was divided into anterior and posterior parts. The anterior strial bed nucleus shows a caudal (older) to rostral (younger) neurogenetic gradient. Cells in the vicinity of the anterior commissural decussation are generated mainly between E13 and E16, cells just posterior to the nucleus accumbens mainly between E15 and E17. Within each rostrocaudal level, neurons originate in combined dorsal to ventral and medial to lateral neurogenetic gradients so that the oldest cells are located ventromedially and the youngest cells dorsolaterally. The most caudal level has some small neurons adjacent to the internal capsule that originate between E17 and E20. In the posterior strial bed nucleus, neurons extend ventromedially into the posterior preoptic area. Cells are generated simultaneously along the rostrocaudal plane in a modified lateral (older) to medial (younger) neurogenetic gradient. Ventrolateral neurons originate mainly between E13 and E16, dorsolateral neurons mainly between E15 and E16, and medial neurons mainly between E15 and E17. The youngest neurons are clumped into a medial core area just ventral to the fornix.

  6. Nuclei-and condition-specific responses to pain in the bed nucleus of the stria terminalis

    PubMed Central

    Morano, Tania J.; Bailey, Nicole J.; Cahill, Catherine M.; Dumont, Éric C.

    2014-01-01

    The bed nucleus of the stria terminalis (BST) is a basal forebrain structure considered to be part of a cortico-striato-pallidal system that coordinates autonomic, neuroendocrine and behavioural physiological responses. Recent evidence suggests that the BST plays a role in the emotional aspect of pain. The objective of the present study was to further understand the neurophysiological bases underlying the involvement of the BST in the pain experience, in both acute and chronic pain conditions. Using c-Fos as an indicator of neuronal activation, the results demonstrated that a single toe-pinch in rats produced nuclei-and condition-specific neuronal responses within the anterior region of the BST (antBST). Specifically, acute noxious stimulation increased c-Fos in the dorsal medial (dAM) and fusiform (FU) nuclei. Chronic neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve decreased the number of c-Fos positive cells following acute mechanical stimulation in the dAM and FU nuclei, and increased c-Fos immunoreactivity in the ventral medial (vAM) aspect of the BST. In addition, the results revealed a nuclei-specific sensitivity to the surgical procedure. Following noxious stimulation to animals that received a sham surgery, c-Fos immunoreactivity was blunted in the FU nucleus while it increased in the oval (OV) nucleus of the BST. Altogether, this study demonstrates that pain induces nuclei-and condition-specific neuronal activation in the BST revealing an intriguing supraspinal neurobiological substrate that may contribute to the physiology of acute nociception and the pathophysiology of chronic pain. PMID:18164529

  7. CRF receptor type 2 neurons in the posterior bed nucleus of the stria terminalis critically contribute to stress recovery.

    PubMed

    Henckens, M J A G; Printz, Y; Shamgar, U; Dine, J; Lebow, M; Drori, Y; Kuehne, C; Kolarz, A; Eder, M; Deussing, J M; Justice, N J; Yizhar, O; Chen, A

    2016-08-23

    The bed nucleus of the stria terminalis (BNST) is critical in mediating states of anxiety, and its dysfunction has been linked to stress-related mental disease. Although the anxiety-related role of distinct subregions of the anterior BNST was recently reported, little is known about the contribution of the posterior BNST (pBNST) to the behavioral and neuroendocrine responses to stress. Previously, we observed abnormal expression of corticotropin-releasing factor receptor type 2 (CRFR2) to be associated with post-traumatic stress disorder (PTSD)-like symptoms. Here, we found that CRFR2-expressing neurons within the pBNST send dense inhibitory projections to other stress-related brain regions (for example, the locus coeruleus, medial amygdala and paraventricular nucleus), implicating a prominent role of these neurons in orchestrating the neuroendocrine, autonomic and behavioral response to stressful situations. Local CRFR2 activation by urocortin 3 depolarized the cells, increased the neuronal input resistance and increased firing of action potentials, indicating an enhanced excitability. Furthermore, we showed that CRFR2-expressing neurons within the pBNST are critically involved in the modulation of the behavioral and neuroendocrine response to stress. Optogenetic activation of CRFR2 neurons in the pBNST decreased anxiety, attenuated the neuroendocrine stress response, ameliorated stress-induced anxiety and impaired the fear memory for the stressful event. Moreover, activation following trauma exposure reduced the susceptibility for PTSD-like symptoms. Optogenetic inhibition of pBNST CRFR2 neurons yielded opposite effects. These data indicate the relevance of pBNST activity for adaptive stress recovery.Molecular Psychiatry advance online publication, 23 August 2016; doi:10.1038/mp.2016.133.

  8. CGRP Antagonist Infused into the Bed Nucleus of the Stria Terminalis Impairs the Acquisition and Expression of Context but Not Discretely Cued Fear

    ERIC Educational Resources Information Center

    Sink, Kelly S.; Davis, Michael; Walker, David L.

    2013-01-01

    Calcitonin gene-related peptide (CGRP) infusions into the bed nucleus of the stria terminalis (BNST) evoke increases in startle amplitude and increases in anxiety-like behavior in the plus maze. Conversely, intra-BNST infusions of the CGRP antagonist CGRP[subscript 8-37] block unconditioned startle increases produced by fox odor. Here we evaluate…

  9. Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders

    PubMed Central

    Lebow, M A; Chen, A

    2016-01-01

    The bed nucleus of the stria terminalis (BNST) is a center of integration for limbic information and valence monitoring. The BNST, sometimes referred to as the extended amygdala, is located in the basal forebrain and is a sexually dimorphic structure made up of between 12 and 18 sub-nuclei. These sub-nuclei are rich with distinct neuronal subpopulations of receptors, neurotransmitters, transporters and proteins. The BNST is important in a range of behaviors such as: the stress response, extended duration fear states and social behavior, all crucial determinants of dysfunction in human psychiatric diseases. Most research on stress and psychiatric diseases has focused on the amygdala, which regulates immediate responses to fear. However, the BNST, and not the amygdala, is the center of the psychogenic circuit from the hippocampus to the paraventricular nucleus. This circuit is important in the stimulation of the hypothalamic–pituitary–adrenal axis. Thus, the BNST has been largely overlooked with respect to its possible dysregulation in mood and anxiety disorders, social dysfunction and psychological trauma, all of which have clear gender disparities. In this review, we will look in-depth at the anatomy and projections of the BNST, and provide an overview of the current literature on the relevance of BNST dysregulation in psychiatric diseases. PMID:26878891

  10. Dopamine decreases NMDA currents in the oval bed nucleus of the stria terminalis of cocaine self-administering rats.

    PubMed

    Krawczyk, Michal; deBacker, Julian; Mason, Xenos; Jones, Andrea A; Dumont, Eric C

    2014-06-03

    Dopamine (DA) and N-methyl-D-aspartate receptors (NMDARs) contribute in the neural processes underlying drug-driven behaviors. DA is a potent modulator of NMDAR, but few studies have investigated the functional interaction between DA and NMDAR in the context of substance abuse. We combined the rat model of cocaine self-administration with brain slice electrophysiology to study DA modulation of NMDA currents in the oval bed nucleus of the stria terminalis (ovBNST), a dense DA terminal field involved in maintenance of cocaine self-administration amongst other drug related behaviors. Long-Evans rats self-administered intravenous cocaine (0.75 mg/kg/injection) on a progressive ratio (PR) schedule of reinforcement for 15 days and whole-cell patch-clamp recordings were done on the 16th day. DA reduced NMDA currents in brain-slices from cocaine self-administering rats, but not in those of drug-naïve and sucrose self-administering, or when cocaine exposure was passive (yoked), revealing a mechanism unique to voluntary cocaine intake. DA reduced NMDA currents by activating G-protein-coupled D1- and D2-like receptors that converged on phospholipase C and protein phosphatases. Accordingly, our study reveals a mechanism that may contribute to dysfunctional synaptic plasticity associated with drug-driven behaviors during acute withdrawal.

  11. Compensation in the neural circuitry of fear conditioning awakens learning circuits in the bed nuclei of the stria terminalis.

    PubMed

    Poulos, Andrew M; Ponnusamy, Ravikumar; Dong, Hong-Wei; Fanselow, Michael S

    2010-08-17

    The basolateral amygdala (BLA) is thought to be essential for fear learning. However, extensive training can overcome the loss of conditional fear evident following lesions and inactivation of the BLA. Such results suggest the existence of a primary BLA-dependent and a compensatory BLA-independent neural circuit. We tested the hypothesis that the bed nuclei of the stria terminalis (BST) provides this compensatory plasticity. Using extensive context-fear conditioning, we demonstrate that combined BLA and BST lesions prevented fear acquisition and expression. Additionally, protein synthesis in the BST was critical only for consolidation of BLA-independent but not BLA-dependent fear. Moreover, fear acquired after BLA lesions resulted in greater activation of BST regions that receive hippocampal efferents. These results suggest that the BST is capable of functioning as a compensatory site in the acquisition and consolidation of context-fear memories. Unlocking such neural compensation holds promise for understanding situations when brain damage impairs normal function or failure to regulate compensatory sites leads to anxiety disorders.

  12. Mechanisms of Neuroplasticity and Ethanol's Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis.

    PubMed

    Lovinger, David M; Kash, Thomas L

    2015-01-01

    Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction.Two brain regions subject to alcohol's effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol's actions and control of intake. The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder.

  13. NMDA-receptor-dependent plasticity in the bed nucleus of the stria terminalis triggers long-term anxiolysis

    PubMed Central

    Glangetas, Christelle; Massi, Léma; Fois, Giulia R.; Jalabert, Marion; Girard, Delphine; Diana, Marco; Yonehara, Keisuke; Roska, Botond; Xu, Chun; Lüthi, Andreas; Caille, Stéphanie; Georges, François

    2017-01-01

    Anxiety is controlled by multiple neuronal circuits that share robust and reciprocal connections with the bed nucleus of the stria terminalis (BNST), a key structure controlling negative emotional states. However, it remains unknown how the BNST integrates diverse inputs to modulate anxiety. In this study, we evaluated the contribution of infralimbic cortex (ILCx) and ventral subiculum/CA1 (vSUB/CA1) inputs in regulating BNST activity at the single-cell level. Using trans-synaptic tracing from single-electroporated neurons and in vivo recordings, we show that vSUB/CA1 stimulation promotes opposite forms of in vivo plasticity at the single-cell level in the anteromedial part of the BNST (amBNST). We find that an NMDA-receptor-dependent homosynaptic long-term potentiation is instrumental for anxiolysis. These findings suggest that the vSUB/CA1-driven LTP in the amBNST is involved in eliciting an appropriate response to anxiogenic context and dysfunction of this compensatory mechanism may underlie pathologic anxiety states. PMID:28218243

  14. Genetic cell targeting uncovers specific neuronal types and distinct subregions in the bed nucleus of the stria terminalis

    PubMed Central

    Nguyen, Amanda Q.; Cruz, Julie A.D. Dela; Sun, Yanjun; Holmes, Todd C.; Xu, Xiangmin

    2017-01-01

    The bed nucleus of the stria terminalis (BNST) plays an important role in fear, stress, and anxiety. It contains a collection of sub-nuclei delineated by gross cytoarchitecture features; however, there has yet to be a systematic examination of specific BNST neuronal types and their associated neurochemical makeup. The present study focuses on improved characterization of the anterior BNST based on differing molecular and chemical expression aided by mouse genetics. Specific Cre driver lines crossed with a fluorescent reporter line were used for genetic cell targeting and immunochemical staining. Using this new approach, we were able to robustly identify specific excitatory and inhibitory cell types in the BNST. The presence and distribution of excitatory neurons were firmly established; glutamatergic neurons in the anterior BNST accounted for about 14% and 31% of dorsal and ventral BNST cells, respectively. GABAergic neurons expressing different isoforms of glutamic acid decarboxylase were found to have differential sub-regional distributions. Almost no parvalbumin-expressing cells were found in the BNST, while somatostatin-expressing cells and calretinin-expressing cells account for modest proportions of BNST cells. In addition, vasoactive intestinal peptide-expressing axonal plexuses were prominent in the oval and juxtacapsular (jc) subregions. In addition, we discovered that corticotropin-releasing hormone (CRH) expressing cells contain GABAergic and glutamatergic subpopulations. Together, this study reveals new information on excitatory and inhibitory neurons in the BNST, which will facilitate genetic dissection and functional studies of BNST subregions. PMID:26718312

  15. Whole-brain mapping of afferent projections to the bed nucleus of the stria terminalis in tree shrews.

    PubMed

    Ni, Rong-Jun; Luo, Peng-Hao; Shu, Yu-Mian; Chen, Ju-Tao; Zhou, Jiang-Ning

    2016-10-01

    The bed nucleus of the stria terminalis (BST) plays an important role in integrating and relaying input information to other brain regions in response to stress. The cytoarchitecture of the BST in tree shrews (Tupaia belangeri chinensis) has been comprehensively described in our previous publications. However, the inputs to the BST have not been described in previous reports. The aim of the present study was to investigate the sources of afferent projections to the BST throughout the brain of tree shrews using the retrograde tracer Fluoro-Gold (FG). The present results provide the first detailed whole-brain mapping of BST-projecting neurons in the tree shrew brain. The BST was densely innervated by the prefrontal cortex, entorhinal cortex, ventral subiculum, amygdala, ventral tegmental area, and parabrachial nucleus. Moreover, moderate projections to the BST originated from the medial preoptic area, supramammillary nucleus, paraventricular thalamic nucleus, pedunculopontine tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and nucleus of the solitary tract. Afferent projections to the BST are identified in the ventral pallidum, nucleus of the diagonal band, ventral posteromedial thalamic nucleus, posterior complex of the thalamus, interfascicular nucleus, retrorubral field, rhabdoid nucleus, intermediate reticular nucleus, and parvicellular reticular nucleus. In addition, the different densities of BST-projecting neurons in various regions were analyzed in the tree shrew brains. In summary, whole-brain mapping of direct inputs to the BST is delineated in tree shrews. These brain circuits are implicated in the regulation of numerous physiological and behavioral processes including stress, reward, food intake, and arousal.

  16. Metabotropic Glutamate Receptor Subtype 7 in the Bed Nucleus of the Stria Terminalis is Essential for Intermale Aggression

    PubMed Central

    Masugi-Tokita, Miwako; Flor, Peter J; Kawata, Mitsuhiro

    2016-01-01

    Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of group III mGluRs, which localize to the presynaptic active zones of the mammalian central nervous system. Although histological, genetic, and electrophysiological studies ensure the importance of mGluR7, its roles in behavior and physiology remain largely unknown. Using a resident–intruder paradigm, we found a severe reduction in intermale aggressive behavior in mGluR7 knockout (KO) mice. We also found alterations in other social behaviors in male mGluR7 KO mice, including sexual behavior toward male intruders. Because olfaction is critical for rodent social behavior, including aggression, we performed an olfaction test, finding that mGluR7 KO mice failed to show interest in the smell of male urine. To clarify the olfactory deficit, we then exposed mice to urine and analyzed c-Fos-immunoreactivity, discovering a remarkable reduction in neural activity in the bed nucleus of the stria terminalis (BNST) of mGluR7 KO mice. Finally, intra-BNST administration of the mGluR7-selective antagonist 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP) also reproduced the phenotype of mGluR7 KO mice, including reduced aggression and altered social interaction. Thus mGluR7 may work as an ‘enhancer of neural activity' in the BNST and is important for intermale aggression. Our findings demonstrate that mGluR7 is essential for social behavior and innate behavior. Our study on mGluR7 in the BNST will shed light on future therapies for emotional disorders in humans. PMID:26149357

  17. The response of neurons in the bed nucleus of the stria terminalis to serotonin: Implications for anxiety

    PubMed Central

    Hammack, Sayamwong E.; Guo, JiDong; Hazra, Rimi; Dabrowska, Joanna; Myers, Karyn M.; Rainnie, Donald G.

    2009-01-01

    Substantial evidence has suggested that the activity of the bed nucleus of the stria terminalis (BNST) mediates many forms of anxiety-like behavior in human and non-human animals. These data have led many investigators to suggest that abnormal processing within this nucleus may underlie anxiety disorders in humans, and effective anxiety treatments may restore normal BNST functioning. Currently some of the most effective treatments for anxiety disorders are drugs that modulate serotonin (5-HT) systems, and several decades of research have suggested that the activation of 5-HT can modulate anxiety-like behavior. Despite these facts, relatively few studies have examined how activity within the BNST is modulated by 5-HT. Here we review our own investigations using in vitro whole-cell patch-clamp electrophysiological methods on brain sections containing the BNST to determine the response of BNST neurons to exogenous 5-HT application. Our data suggest that the response of BNST neurons to 5-HT is complex, displaying both inhibitory and excitatory components, which are mediated by 5-HT1A, 5-HT2A, 5-HT2C and 5-HT7 receptors. Moreover, we have shown that the selective activation of the inhibitory response to 5-HT reduces anxiety-like behavior, and we describe data suggesting that the activation of the excitatory response to 5-HT may be anxiogenic. We propose that in the normal state, the function of 5-HT is to dampen activity within the BNST (and consequent anxiety-like behavior) during exposure to threatening stimuli; however, we suggest that changes in the balance of the function of BNST 5-HT receptor subtypes could alter the response of BNST neurons to favor excitation and produce a pathological state of increase anxiety. PMID:19467288

  18. Interactions of norepinephrine and galanin in the central amygdala and lateral bed nucleus of the stria terminalis modulate the behavioral response to acute stress.

    PubMed

    Morilak, David A; Cecchi, Marco; Khoshbouei, Habibeh

    2003-06-27

    Many aspects of drug abuse and addiction share neurobiological substrates with the modulatory processes underlying the response and adaptation to acute stress. In particular, the ascending noradrenergic system has been implicated in facilitating the response to stress, and in stress-induced reinstatement of drug seeking behavior. Thus, to better understand the link between stress and addictive behaviors, it would be informative to understand better the modulatory function of the ascending noradrenergic system, and its interaction with other neurotransmitters with which it is closely associated or co-localized, such as the neuropeptide galanin. In this paper, we review a series of studies investigating the functional interactions of norepinephrine and galanin in modulating the behavioral response to acute stress in two components of the extended amygdala, the central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis. We showed that norepinephrine facilitates behavioral reactivity to stress on the elevated plus-maze and social interaction tests. However, when stress-induced activation of the noradrenergic system was enhanced by blocking inhibitory adrenergic autoreceptors, galanin release was recruited in the central amygdala, acting to attenuate the behavioral response to stress. By contrast, stress-induced galanin release in the lateral bed nucleus appeared to be independent of enhanced noradrenergic activation, and unlike the central amygdala, both galanin and norepinephrine facilitated behavioral stress reactivity in the bed nucleus. The different modes of interaction and differential region- and response-specificity of galanin and norepinephrine suggest that a complex neural circuit interconnecting these two regions is involved in the modulatory effects of norepinephrine and galanin on the behavioral response to stress. Such complexity may allow for flexibility and plasticity in stress adaptation, and may also contribute to behavioral

  19. PAC1 receptor antagonism in the bed nucleus of the stria terminalis (BNST) attenuates the endocrine and behavioral consequences of chronic stress

    PubMed Central

    Roman, Carolyn W.; Lezak, Kim R.; Hartsock, Matthew J.; Falls, William A.; Braas, Karen M.; Howard, Alan B.; Hammack, Sayamwong E.; May, Victor

    2015-01-01

    Summary Chronic or repeated stressor exposure can induce a number of maladaptive behavioral and physiological consequences and among limbic structures, the bed nucleus of the stria terminalis (BNST) has been implicated in the integration and interpretation of stress responses. Previous work has demonstrated that chronic variate stress (CVS) exposure in rodents increases BNST pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) and PAC1 receptor (Adcyap1r1) transcript expression, and that acute BNST PACAP injections can stimulate anxiety-like behavior. Here we show that chronic stress increases PACAP expression selectively in the oval nucleus of the dorsolateral BNST in patterns distinct from those for corticotropin releasing hormone (CRH). Among receptor subtypes, BNST PACAP signaling through PAC1 receptors not only heightened anxiety responses as measured by different behavioral parameters but also induced anorexic-like behavior to mimic the consequences of stress. Conversely, chronic inhibition of BNST PACAP signaling by continuous infusion with the PAC1 receptor antagonist PACAP(6-38) during the week of CVS attenuated these stress-induced behavioral responses and changes in weight gain. BNST PACAP signaling stimulated the hypothalamic-pituitary-adrenal (HPA) axis and heightened corticosterone release; further, BNST PACAP(6-38) administration blocked corticosterone release in a sensitized stress model. In aggregate with recent associations of PACAP/PAC1 receptor dysregulation with altered stress responses including post-traumatic stress disorder, these data suggest that BNST PACAP/PAC1 receptor signaling mechanisms may coordinate the behavioral and endocrine consequences of stress. PMID:25001965

  20. Role of bed nucleus of the stria terminalis and amygdala AMPA receptors in the development and expression of context conditioning and sensitization of startle by prior shock

    PubMed Central

    Davis, Michael

    2013-01-01

    A core symptom of post-traumatic stress disorder is hyper-arousal—manifest in part by increases in the amplitude of the acoustic startle reflex. Gewirtz et al. (Prog Neuropsychopharmacol Biol Psychiatry 22:625–648, 1998) found that, in rats, persistent shock-induced startle increases were prevented by pre-test electrolytic lesions of the bed nucleus of the stria terminalis (BNST). We used reversible inactivation to determine if similar effects reflect actions on (a) BNST neurons themselves versus fibers-of-passage, (b) the development versus expression of such increases, and (c) associative fear versus non-associative sensitization. Twenty-four hours after the last of three shock sessions, startle was markedly enhanced when rats were tested in a non-shock context. These increases decayed over the course of several days. Decay was unaffected by context exposure, and elevated startle was restored when rats were tested for the first time in the original shock context. Thus, both associative and non-associative components could be measured under different conditions. Pre-test intra-BNST infusions of the AMPA receptor antagonist NBQX (3 μg/side) blocked the non-associative (as did infusions into the basolateral amygdala) but not the associative component, whereas pre-shock infusions disrupted both. NBQX did not affect baseline startle or shock reactivity. These results indicate that AMPA receptors in or very near to the BNST are critical for the expression and development of non-associative shock-induced startle sensitization, and also for context fear conditioning, but not context fear expression. More generally, they suggest that treatments targeting the BNST may be clinically useful for treating trauma-related hyper-arousal and perhaps for retarding its development. PMID:23934654

  1. Projections from Bed Nuclei of the Stria Terminalis, Anteromedial Area: Cerebral Hemisphere Integration of Neuroendocrine, Autonomic, and Behavioral Aspects of Energy Balance

    PubMed Central

    DONG, HONG-WEI; SWANSON, LARRY W.

    2008-01-01

    The anteromedial area of the bed nuclei of the stria terminalis (BSTam) is the relatively undifferentiated region of the anterior medial (anteromedial) group of the bed nuclei of the stria terminalis (BSTamg), which also includes the more distinct dorsomedial, magnocellular, and ventral nuclei. The overall pattern of axonal projections from the rat BSTam was analyzed with the PHAL anterograde pathway tracing method. Brain areas receiving relatively moderate to strong inputs from the BSTam fall into five general categories: neuroendocrine system (regions containing pools of magnocellular oxytocin neurons, and parvicellular corticotropin-releasing hormone, thyrotropin-releasing hormone, somatostatin, and dopamine neurons); central autonomic control network (central amygdalar nucleus, descending paraventricular nucleus, and ventrolateral periaqueductal gray); hypothalamic visceromotor pattern generator network (5 of 6 known components); behavior control column (descending paraventricular nucleus and associated arcuate nucleus; ventral tegmental area and associated nucleus accumbens and substantia innominata); and behavioral state control (supramammillary and tuberomammillary nuclei). The BSTam projects lightly to thalamocortical feedback loops (via the medial-midline-intralaminar thalamus). Its pattern of axonal projections, combined with its pattern of neural inputs (the most varied of all BST cell groups), suggest that the BSTam is part of a striatopallidal differentiation involved in coordinating neuroendocrine, autonomic, and behavioral or somatic responses associated with maintaining energy balance homeostasis. PMID:16304685

  2. Reversible Inactivation of the Bed Nucleus of the Stria Terminalis Prevents Reinstatement But Not Renewal of Extinguished Fear1,2,3

    PubMed Central

    Goode, Travis D.; Kim, Janice J.

    2015-01-01

    Abstract The extinction of conditioned fear is labile. For example, fear to an extinguished conditioned stimulus (CS) returns after presentation of an aversive stimulus (“reinstatement”) or a change in context (“renewal”). Substantial research implicates the bed nucleus of the stria terminalis (BNST) in the stress-induced relapse of extinguished behaviors, such as in instrumental drug seeking, but its role in the relapse of extinguished fear responses is not clear. Here, we explored the role of the BNST in both the reinstatement and renewal of fear, two forms of relapse that are differentially triggered by stress. In Experiment 1, rats received pairings of an auditory CS and footshock unconditioned stimulus (US) followed by an extinction procedure. After extinction, rats received an unsignaled US to reinstate fear to the extinguished CS. Twenty-four hours later, they were infused with either muscimol or vehicle into the BNST immediately prior to a CS retrieval test. In Experiment 2, rats were conditioned and extinguished in two distinct contexts. Twenty-four hours after extinction, the rats were infused with muscimol, NBQX, or vehicle immediately prior to a CS retrieval test in either the extinction context or a different (but familiar) context. In both experiments, freezing behavior served as the index of conditioned fear. The results revealed that BNST inactivation prevented reinstatement (Experiment 1), but not renewal (Experiment 2), of conditioned freezing to the extinguished CS. Hence, the BNST is critical for the reinstatement of extinguished fear in an aversive context, but not for the contextual retrieval processes that mediate fear renewal. PMID:26464990

  3. Efferent projection from the bed nucleus of the stria terminalis suppresses activity of taste-responsive neurons in the hamster parabrachial nuclei.

    PubMed

    Li, Cheng-Shu; Cho, Young K

    2006-10-01

    Although the reciprocal projections between the bed nucleus of the stria terminalis (BNST) and the gustatory parabrachial nuclei (PbN) have been demonstrated neuroanatomically, there is no direct evidence showing that the projections from the PbN to the BNST carry taste information or that descending inputs from the BNST to the PbN modulate the activity of PbN gustatory neurons. A recent electrophysiological study has demonstrated that the BNST exerts modulatory influence on taste neurons in the nucleus of the solitary tract (NST), suggesting that the BNST may also modulate the activity of taste neurons in the PbN. In the present study, we recorded from 117 taste-responsive neurons in the PbN and examined their responsiveness to electrical stimulation of the BNST bilaterally. Thirteen neurons (11.1%) were antidromically invaded from the BNST, mostly from the ipsilateral side (12 cells), indicating that a subset of taste neurons in the PbN project their axons to the BNST. The BNST stimulation induced orthodromic responses on most of the PbN neurons: 115 out of 117 (98.3%), including all BNST projection units. This descending modulation on the PbN gustatory neurons was exclusively inhibitory. We also confirmed that activation of this efferent inhibitory projection from the BNST reduces taste responses of PbN neurons in all units tested. The BNST is part of the neural circuits that involve stress-associated feeding behavior. It is also known that brain stem gustatory nuclei, including the PbN, are associated with feeding behavior. Therefore, this neural substrate may be important in the stress-elicited alteration in ingestive behavior.

  4. A corticotropin releasing factor pathway for ethanol regulation of the ventral tegmental area in the bed nucleus of the stria terminalis.

    PubMed

    Silberman, Yuval; Matthews, Robert T; Winder, Danny G

    2013-01-16

    A growing literature suggests that catecholamines and corticotropin-releasing factor (CRF) interact in a serial manner to activate the bed nucleus of the stria terminalis (BNST) to drive stress- or cue-induced drug- and alcohol-seeking behaviors. Data suggest that these behaviors are driven in part by BNST projections to the ventral tegmental area (VTA). Together, these findings suggest the existence of a CRF-signaling pathway within the BNST that is engaged by catecholamines and regulates the activity of BNST neurons projecting to the VTA. Here we test three aspects of this model to determine: (1) whether catecholamines modify CRF neuron activity in the BNST; (2) whether CRF regulates excitatory drive onto VTA-projecting BNST neurons; and (3) whether this system is altered by ethanol exposure and withdrawal. A CRF neuron fluorescent reporter strategy was used to identify BNST CRF neurons for whole-cell patch-clamp analysis in acutely prepared slices. Using this approach, we found that both dopamine and isoproterenol significantly depolarized BNST CRF neurons. Furthermore, using a fluorescent microsphere-based identification strategy we found that CRF enhances the frequency of spontaneous EPSCs onto VTA-projecting BNST neurons in naive mice. This action of CRF was occluded during acute withdrawal from chronic intermittent ethanol exposure. These findings suggest that dopamine and isoproterenol may enhance CRF release from local BNST sources, leading to enhancement of excitatory neurotransmission on VTA-projecting neurons, and that this pathway is engaged by patterns of alcohol exposure and withdrawal known to drive excessive alcohol intake.

  5. Maternally responsive neurons in the bed nucleus of the stria terminalis and medial preoptic area: putative circuits for regulating anxiety and reward

    PubMed Central

    McHenry, Jenna A.; Rubinow, David R.; Stuber, Garret D

    2016-01-01

    Postpartum neuropsychiatric disorders are a major source of morbidity and mortality and affect at least 10% of childbearing women. Affective dysregulation within this context has been identified in association with changes in reproductive steroids. Steroids promote maternal actions and modulate affect, but can also destabilize mood in some but not all women. Potential brain regions that mediate these effects include the medial preoptic area (mPOA) and ventral bed nucleus of the stria terminalis (vBNST). Herein, we review the regulation of neural activity in the mPOA/vBNST by environmental and hormonal concomitants in puerperal females. Such activity may influence maternal anxiety and motivation and have significant implications for postpartum affective disorders. Future directions for research are also explored, including physiological circuit-level approaches to gain insight into the functional connectivity of hormone-responsive maternal circuits that modulate affect. PMID:25910426

  6. Sex chromosome complement determines sex differences in aromatase expression and regulation in the stria terminalis and anterior amygdala of the developing mouse brain.

    PubMed

    Cisternas, Carla D; Tome, Karina; Caeiro, Ximena E; Dadam, Florencia M; Garcia-Segura, Luis M; Cambiasso, María J

    2015-10-15

    Aromatase, which converts testosterone in estradiol, is involved in the generation of brain sex dimorphisms. Here we used the "four core genotypes" mouse model, in which the effect of gonadal sex and sex chromosome complement is dissociated, to determine if sex chromosomes influence the expression of brain aromatase. The brain of 16 days old XY mouse embryos showed higher aromatase expression in the stria terminalis and the anterior amygdaloid area than the brain of XX embryos, independent of gonadal sex. Furthermore, estradiol or dihydrotestosterone increased aromatase expression in cultures of anterior amygdala neurons derived from XX embryos, but not in those derived from XY embryos. This effect was also independent of gonadal sex. The expression of other steroidogenic molecules, estrogen receptor-α and androgen receptor was not influenced by sex chromosomes. In conclusion, sex chromosomes determine sex dimorphisms in aromatase expression and regulation in the developing mouse brain.

  7. Corticotropin-releasing factor type II (CRF-sub-2) receptors in the bed nucleus of the stria terminalis modulate conditioned defeat in Syrian hamsters (Mesocricetus auratus).

    PubMed

    Cooper, Matthew A; Huhman, Kim L

    2005-08-01

    In Syrian hamsters (Mesocricetus auratus), social defeat produces a subsequent increase in submissive and defensive behavior and a loss of normal territorial aggression, which the authors have called conditioned defeat. In this study, the authors investigated the effect of blocking corticotropin-releasing factor (CRF) Type I and Type II receptors on conditioned defeat. Intracerebroventricular infusion of the CRF-sub-2 receptor antagonist antisauvagine-30 prior to testing significantly reduced conditioned defeat compared with vehicle controls, whereas the CRF-sub-1 receptor antagonist CP-154,526 had no effect. Also, infusion of antisauvagine-30 into the bed nucleus of the stria terminalis (BNST) 15 min, but not immediately, prior to testing reduced conditioned defeat in a dose-dependent manner. The authors' results provide evidence that CRF-sub-2 receptors in the BNST, but not CRF-sub-1 receptors, are an important component in the neural circuitry regulating conditioned defeat.

  8. Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat.

    PubMed

    Nasimi, Ali; Kafami, Marzieh

    2016-07-01

    The bed nucleus of the stria terminalis (BST) is involved in cardiovascular regulation. The angiotensin II (Ang II) receptor (AT1), and angiotensinogen were found in the BST. In our previous study we found that microinjection of Ang II into the BST produced a pressor response. This study was performed to find the mechanisms mediating this response in anesthetized rats. Ang II was microinjected into the BST and the cardiovascular responses were re-tested after systemic injection of a blocker of autonomic or vasopressin V1 receptor. The ganglionic nicotinic receptor blocker, hexamethonium dichloride, attenuated the pressor response to Ang II, indicating that the cardiovascular sympathetic system is involved in the pressor effect of Ang II. A selective vasopressin V1 receptor antagonist greatly attenuated the pressor effect of Ang II, indicating that the Ang II increases the arterial pressure via stimulation of vasopressin release as well. In conclusion, in the BST, Ang II as a neurotransmitter increases blood pressure by exciting cardiovascular sympathetic system and directly or indirectly causing vasopressin to release into bloodstream by VPN. This is an interesting new finding that not only circulating Ang II but also brain Ang II makes vasopressin release.

  9. Projections from Bed Nuclei of the Stria Terminalis, Magnocellular Nucleus: Implications for Cerebral Hemisphere Regulation of Micturition, Defecation, and Penile Erection

    PubMed Central

    DONG, HONG-WEI; SWANSON, LARRY W.

    2008-01-01

    The basic structural organization of axonal projections from the small but distinct magnocellular and ventral nuclei (of the bed nuclei of the stria terminalis) were analyzed with the PHAL anterograde tract tracing method in adult male rats. The former's overall projection pattern is complex, with over 80 distinct terminal fields ipsilateral to injection sites. Innervated regions in the cerebral hemisphere and brainstem fall into 9 general functional categories: cerebral nuclei, behavior control column, orofacial motor-related, humorosensory/thirst-related, brainstem autonomic control network, neuroendocrine, hypothalamic visceromotor pattern generator network, thalamocortical feedback loops, and behavioral state control. The most novel findings indicate that the magnocellular nucleus projects to virtually all known major parts of the brain network that controls pelvic functions including micturition, defecation, and penile erection—as well as to brain networks controlling nutrient and body water homeostasis. This and other evidence suggests that the magnocellular nucleus is part of a cortico-striatopallidal differentiation modulating and coordinating pelvic functions with the maintenance of nutrient and body water homeostasis. Projections of the ventral nucleus are a subset of those generated by the magnocellular nucleus, with the obvious difference that the ventral nucleus does not project detectably to Barrington's nucleus, the subfornical organ, the median preoptic and parastrial nuclei, the neuroendocrine system, and midbrain orofacial motor-related regions. PMID:16304682

  10. Projections from Bed Nuclei of the Stria Terminalis, Dorsomedial Nucleus: Implications for Cerebral Hemisphere Integration of Neuroendocrine, Autonomic, and Drinking Responses

    PubMed Central

    DONG, HONG-WEI; SWANSON, LARRY W.

    2008-01-01

    The overall projection pattern of a tiny bed nuclei of the stria terminalis anteromedial group differentiation, the dorsomedial nucleus (BSTdm), was analyzed with the PHAL anterograde pathway-tracing method in rats. Many brain regions receive a relatively moderate to strong input from the BSTdm. They fall into 8 general categories: humeral sensory-related (subfornical organ and median preoptic nucleus—involved in initiating drinking behavior and salt appetite), neuroendocrine system (magnocellular: oxytocin, vasopressin; parvicellular: gonadotropin-releasing hormone, somatostatin, thyrotropin-releasing hormone, corticotropin-releasing hormone), central autonomic control network (central amygdalar nucleus, BST anterolateral group, descending paraventricular hypothalamic nucleus, retrochiasmatic area, ventrolateral periaqueductal gray, Barrington's nucleus), hypothalamic visceromotor pattern generator network (5 of 6 known components), behavior control column (ingestive: descending paraventricular nucleus; reproductive: lateral medial preoptic nucleus; defensive: anterior hypothalamic nucleus; foraging: ventral tegmental area, along with interconnected nucleus accumbens and substantia innominata), orofacial motor control (retrorubral area), thalamocortical feedback loops (paraventricular, central medial, intermediodorsal, and medial mediodorsal nuclei; nucleus reuniens), and behavioral state control (subparaventricular zone, ventrolateral preoptic nucleus, tuberomammillary nucleus, supramammillary nucleus, lateral habenula, and raphé nuclei). This pattern of axonal projections, and what little is known of its inputs, suggest that the BSTdm is part of a striatopallidal differentiation involved in coordinating the homeostatic and behavioral responses associated thirst and salt appetite, although clearly it may relate them to other functions as well. The BSTdm generates the densest known inputs directly to the neuroendocrine system from any part of the cerebral

  11. Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition

    PubMed Central

    Dumais, Kelly M.; Alonso, Andrea G.; Immormino, Marisa A.; Bredewold, Remco; Veenema, Alexa H.

    2015-01-01

    Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5 ng/0.5 μl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100 pg/0.5 μl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition. PMID:26630388

  12. In Vivo Voltammetric Monitoring of Norepinephrine Release in the Rat Ventral Bed Nucleus of the Stria Terminalis and Anteroventral Thalamic Nucleus

    PubMed Central

    Park, Jinwoo; Kile, Brian M.; Wightman, R. Mark

    2010-01-01

    The role and contribution of the dense noradrenergic innervation in the ventral bed nucleus of the stria terminalis (vBNST) and anteroventral thalamic nucleus (AV) to biological function and animal behaviors is poorly understood due to the small size of these nuclei. The aim of this study was to compare norepinephrine release and uptake in the vBNST with that in the AV of anesthetized rats. Measurements were made in vivo with fast-scan cyclic voltammetry following electrical stimulation of noradrenergic projection pathways, either the dorsal noradrenergic bundle (DNB) or the ventral noradrenergic bundle (VNB). The substance detected was identified as norepinephrine based upon voltammetric, anatomical, neurochemical, and pharmacological evidence. Fast-scan cyclic voltammetry enables the selective monitoring of local norepinephrine overflow in the vBNST evoked by the stimulation of either the DNB or VNB while norepinephrine in the AV was only evoked by DNB stimulation. The α2-adrenoceptor antagonist, yohimbine, and the norepinephrine uptake inhibitor, desipramine, increased norepinephrine overflow and slowed its disappearance in both regions. However, control of extracellular norepinephrine by both autoreceptors and uptake was greater in the AV. The greater control exerted by autoreceptors and uptake in the AV resulted in reduced extracellular concentration compared to the vBNST when large numbers of stimulation pulses were employed. The differences in noradrenergic transmission observed in the terminal fields of the vBNST and the AV may differentially regulate activity in these two regions that both contain high densities of norepinephrine terminals. PMID:20128849

  13. GABA and NMDA receptors in CRF neurons have opposing effects in fear acquisition and anxiety in central amygdala vs. bed nucleus of the stria terminalis.

    PubMed

    Gafford, Georgette M; Ressler, Kerry J

    2015-11-01

    This article is part of a Special Issue "SBN 2014". Beginning with Vale and Colleagues in 1981, corticotropin releasing factor (CRF) also called corticotropin releasing hormone (CRH) has repeatedly been identified as an important contributor to fear and anxiety behavior. These findings have proven useful to further our understanding of disorders that have significant fear-dysregulation, such as post-traumatic stress, as well as other stress- and anxiety-related disorders. Unfortunately, the data are not all in agreement. In particular the role of CRF in fear learning is controversial, with studies pointing to contradictory effects from CRF manipulation even within the same brain structure. Further, very few studies address the potentially promising role of CRF manipulation in fear extinction behavior. Here, we briefly review the role of CRF in anxiety, fear learning and extinction, focusing on recent cell-type and neurotransmitter-specific studies in the amygdala and bed nucleus of the stria terminalis (BNST) that may help to synthesize the available data on the role of CRF in fear and anxiety-related behaviors.

  14. Emerging role for corticotropin releasing factor signaling in the bed nucleus of the stria terminalis at the intersection of stress and reward.

    PubMed

    Silberman, Yuval; Winder, Danny G

    2013-01-01

    Stress and anxiety play an important role in the development and maintenance of drug and alcohol addiction. The bed nucleus of the stria terminalis (BNST), a brain region involved in the production of long-term stress-related behaviors, plays an important role in animal models of relapse, such as reinstatement to previously extinguished drug-seeking behaviors. While a number of neurotransmitter systems have been suggested to play a role in these behaviors, recent evidence points to the neuropeptide corticotropin releasing factor (CRF) as being critically important in BNST-mediated reinstatement behaviors. Although numerous studies indicate that the BNST is a complex brain region with multiple afferent and efferent systems and a variety of cell types, there has only been limited work to determine how CRF modulates this complex neuronal system at the circuit level. Recent work from our lab and others have begun to unravel these BNST neurocircuits and explore their roles in CRF-related reinstatement behaviors. This review will examine the role of CRF signaling in drug addiction and reinstatement with an emphasis on critical neurocircuitry within the BNST that may offer new insights into treatments for addiction.

  15. CALCITONIN GENE-RELATED PEPTIDE IN THE BED NUCLEUS OF THE STRIA TERMINALIS PRODUCES AN ANXIETY-LIKE PATTERN OF BEHAVIOR AND INCREASES NEURAL ACTIVATION IN ANXIETY-RELATED STRUCTURES

    PubMed Central

    Sink, KS; Walker, DL; Yang, Y; Davis, M

    2011-01-01

    Calcitonin gene-related peptide (CGRP) evokes anxiety-like responses when infused into the lateral ventricle of rats. Because the bed nucleus of the stria terminalis (BNST) lies immediately adjacent to the lateral ventricle, is rich in CGRP receptors, and has itself been implicated in anxiety, we evaluated the hypothesis that these effects are attributable to stimulation of CGRP receptors within the BNST itself. Bilateral intra-BNST, but not dorsal, CGRP infusions (0, 200, 400, 800 ng/side) dose-dependently enhanced startle amplitude, and produced an anxiety-like response on the elevated plus maze. Intra-BNST infusion of the CGRP antagonist, αCGRP8-37, blocked the effect of CGRP on startle, and also blocked startle potentiation produced by exposure to trimethylthiazoline (TMT – a component of fox feces that induces anxiety-like behavior in rats). Intra-BNST, but not dorsal, CGRP infusions also increased c-Fos immunoreactivity in a number of anxiety-related brain areas (central nucleus of the amygdala, locus coeruleus, ventrolateral septal nucleus, paraventricular hypothalamic nucleus, lateral hypothalamus, lateral parabrachial nucleus, dorsal raphe nucleus, and nucleus accumbens shell), all of which receive direct projections from the BNST. Together, the results indicate that the activation of BNST CGRP receptors is both necessary and sufficient for some anxiety responses and that these effects may be mediated by activation of a wider network of BNST efferent structures. If so, inhibition of CGRP receptors may be a clinically useful strategy for anxiety reduction. PMID:21289190

  16. Dissociation in control of physiological and behavioral responses to emotional stress by cholinergic neurotransmission in the bed nucleus of the stria terminalis in rats.

    PubMed

    Gouveia, Marianna K; Miguel, Tarciso T; Busnardo, Cristiane; Scopinho, América A; Corrêa, Fernando M A; Nunes-de-Souza, Ricardo L; Crestani, Carlos C

    2016-02-01

    The bed nucleus of the stria terminalis (BNST) is a forebrain structure implicated in physiological and behavioral responses to emotional stress. However, the local neurochemical mechanisms mediating the BNST control of stress responses are not fully known. Here, we investigated the involvement of BNST cholinergic neurotransmission, acting via muscarinic receptors, in cardiovascular (increase in blood pressure and heart rate and fall in tail skin temperature) and neuroendocrine (increase in plasma corticosterone) responses and behavioral consequences (anxiogenic-like effect in the elevated plus-maze) evoked by acute restraint stress in rats. Bilateral microinjection into the BNST of either the choline uptake inhibitor hemicholinium-3 (3 nmol/100 nl) or the muscarinic receptor antagonist methylatropine (3 nmol/100 nl) enhanced the heart rate increase and inhibited the anxiogenic-like effect observed in the elevated plus-maze evoked by restraint. However, neither hemicholinium-3 nor methylatropine affected the increase in blood pressure and plasma corticosterone levels and the fall in tail skin temperature. Facilitation of local cholinergic signaling by microinjection of the acetylcholinesterase inhibitor neostigmine (0.1 nmol/100 nl) into the BNST reduced restraint-evoked pressor and tachycardiac responses and the fall in tail cutaneous temperature, without affecting the increase in plasma corticosterone. All effects of neostigmine were completely abolished by local BNST pretreatment with methylatropine. These findings indicate an opposite role of BNST cholinergic neurotransmission, acting via local muscarinic receptor, in control of cardiovascular responses (inhibitory influence) and emotional consequences (facilitatory influence) evoked by restraint stress. Furthermore, present findings provide evidence that BNST control of neuroendocrine responses to stress is mediated by mechanisms others than local cholinergic signaling.

  17. Common and distinct neural inputs to the medial central nucleus of the amygdala and anterior ventrolateral bed nucleus of stria terminalis in rats

    PubMed Central

    Bienkowski, Michael S.

    2013-01-01

    The central nucleus of the amygdala (CEA) and lateral bed nucleus of stria terminalis (BST) are highly interconnected limbic forebrain regions that share similar connectivity with other brain regions that coordinate behavioral and physiological responses to internal and environmental stressors. Their similar connectivity is frequently referred to when describing the CEA and lateral BST together as a unified “central extended amygdala”. However, the CEA and BST reportedly play distinct roles in behavioral and physiological responses associated with fear, anxiety, and social defeat, presumably due to differences in connectivity. To identify common and unique sources of input to the CEA and lateral BST, we performed dual retrograde tracing. Fluorogold and cholera toxin β were iontophoresed into the medial CEA (CEAm) and the anterior ventrolateral BST (BSTvl) of adult male rats. The anatomical distribution of tracer-labeled neurons was mapped throughout the brain. Regions with overlapping populations of CEAm- and BSTvl-projecting neurons were further examined for the presence of double-labeled neurons. Although most regions with input to the mCEA also projected to the BSTvl, and vice versa, cortical and sensory system-related regions projected more robustly to the CEAm, while motor system-related regions primarily innervated the BSTvl. The incidence of double-labeled neurons with collateralized axonal inputs to the CEAm and BSTvl was relatively small (~2 to 13%) and varied across regions, suggesting regional differences in the degree of coordinated CEAm and BSTvl input. The demonstrated similarities and differences in inputs to CEAm and BSTvl provide new anatomical insights into the functional organization of these limbic forebrain regions. PMID:22362201

  18. The bed nucleus of the stria terminalis is critical for sexual solicitation, but not for opposite-sex odor preference, in female Syrian hamsters.

    PubMed

    Martinez, Luis A; Petrulis, Aras

    2011-11-01

    Successful reproduction in vertebrates depends critically upon a suite of precopulatory behaviors that occur prior to mating. In Syrian hamsters (Mesocricetus auratus), these behaviors include vaginal scent marking and preferential investigation of male odors. The neural regulation of vaginal marking and opposite-sex odor preference likely involves an interconnected set of steroid-sensitive nuclei that includes the medial amygdala (MA), the bed nucleus of the stria terminalis (BNST), and the medial preoptic area (MPOA). For example, lesions of MA eliminate opposite-sex odor preference and reduce overall levels of vaginal marking, whereas lesions of MPOA decrease vaginal marking in response to male odors. Although BNST is densely interconnected with both MA and MPOA, little is known about the role of BNST in female precopulatory behaviors. To address this question, females received either bilateral, excitotoxic lesions of BNST (BNST-X) or sham lesions (SHAM), and were tested for scent marking and for investigatory responses to male and female odors. Whereas SHAM females vaginal marked more to male odors than female odors on two days of the estrous cycle, BNST-X females marked at equivalent levels to both odors. This deficit is not due to alterations in social odor investigation, as both BNST-X and SHAM females investigated male odors more than female odors. Finally, BNST lesions did not generally disrupt the cyclic changes in reproductive behaviors that occur across the estrous cycle. Taken together, these results demonstrate that BNST is critical for the normal expression of solicitational behaviors by females in response to male odor stimuli.

  19. Chemosensory and hormone information are relayed directly between the medial amygdala, posterior bed nucleus of the stria terminalis, and medial preoptic area in male Syrian hamsters

    PubMed Central

    Been, Laura E.; Petrulis, Aras

    2011-01-01

    In many rodent species, including Syrian hamsters, the expression of appropriate social behavior depends critically on the perception and identification of conspecific odors. The behavioral response to these odors is mediated by a network of steroid-sensitive ventral forebrain nuclei including the medial amygdala (Me), posterior bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA). Although it is well-known that Me, BNST, and MPOA are densely interconnected and each uniquely modulates odor-guided social behaviors, the degree to which conspecific odor information and steroid hormone cues are directly relayed between these nuclei is unknown. To answer this question, we injected the retrograde tracer, cholera toxin B (CTB), into the BNST or MPOA of male subjects and identified whether retrogradely-labeled cells in Me and BNST 1) expressed immediate early genes (IEGs) following exposure to male and/or female odors or 2) expressed androgen receptor (AR). Although few retrogradely-labeled cells co-localized with IEGs, a higher percentage of BNST- and MPOA-projecting cells in the posterior Me (MeP) expressed IEGs in response to female odors than to male odors. The percentage of retrogradely-labeled cells that expressed IEGs did not, however, differ between and female- and male- odor-exposed groups in the anterior Me (MeA), posterointermediate BNST (BNSTpi), or posteromedial BNST (BNSTpm). Many retrogradely-labeled cells co-localized with AR, and a higher percentage of retrogradely-labeled MeP and BNSTpm cells expressed AR than retrogradely-labeled MeA and BNSTpi cells, respectively. Together, these data demonstrate that Me, BNST, and MPOA interact as a functional circuit to process sex-specific odor cues and hormone information in male Syrian hamsters. PMID:21316366

  20. Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala

    PubMed Central

    Tsuneoka, Yousuke; Tsukahara, Shinji; Yoshida, Sachine; Takase, Kenkichi; Oda, Satoko; Kuroda, Masaru; Funato, Hiromasa

    2017-01-01

    The brain shows various sex differences in its structures. Various mammalian species exhibit sex differences in the sexually dimorphic nucleus of the preoptic area (SDN-POA) and parts of the extended amygdala such as the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr) and posterodorsal part of the medial amygdala (MePD). The SDN-POA and BNSTpr are male-biased sexually dimorphic nuclei, and characterized by the expression of calbindin D-28K (calbindin 1). However, calbindin-immunoreactive cells are not restricted to the SDN-POA, but widely distributed outside of the SDN-POA. To find genes that are more specific to sexually dimorphic nuclei, we selected candidate genes by searching the Allen brain atlas and examined the detailed expressions of the candidate genes using in situ hybridization. We found that the strong expression of monooxygenase DBH-like 1 (Moxd1) was restricted to the SDN-POA, BNSTpr and MePD. The numbers of Moxd1-positive cells in the SDN-POA, BNSTpr and MePD in male mice were larger than those in female mice. Most of the Moxd1-positive cells in the SDN-POA and BNSTpr expressed calbindin. Neonatal castration of male mice reduced the number of Moxd1-positive cells in the SDN-POA, whereas gonadectomy in adulthood did not change the expression of the Moxd1 gene in the SDN-POA in both sexes. These results suggest that the Moxd1 gene is a suitable marker for sexual dimorphic nuclei in the POA, BNST and amygdala, which enables us to manipulate sexually dimorphic neurons to examine their roles in sex-biased physiology and behaviors.

  1. Regional difference in sex steroid action on formation of morphological sex differences in the anteroventral periventricular nucleus and principal nucleus of the bed nucleus of the stria terminalis.

    PubMed

    Kanaya, Moeko; Tsuda, Mumeko C; Sagoshi, Shoko; Nagata, Kazuyo; Morimoto, Chihiro; Thu, Chaw Kyi Tha; Toda, Katsumi; Kato, Shigeaki; Ogawa, Sonoko; Tsukahara, Shinji

    2014-01-01

    Sex steroid action is critical to form sexually dimorphic nuclei, although it is not fully understood. We previously reported that masculinization of the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), which is larger and has more neurons in males than in females, involves aromatized testosterone that acts via estrogen receptor-α (ERα), but not estrogen receptor-β (ERβ). Here, we examined sex steroid action on the formation of the anteroventral periventricular nucleus (AVPV) that is larger and has more neurons in females. Morphometrical analysis of transgenic mice lacking aromatase, ERα, or ERβ genes revealed that the volume and neuron number of the male AVPV were significantly increased by deletion of aromatase and ERα genes, but not the ERβ gene. We further examined the AVPV and BNSTp of androgen receptor knockout (ARKO) mice. The volume and neuron number of the male BNSTp were smaller in ARKO mice than those in wild-type mice, while no significant effect of ARKO was found on the AVPV and female BNSTp. We also examined aromatase, ERα, and AR mRNA levels in the AVPV and BNSTp of wild-type and ARKO mice on embryonic day (ED) 18 and postnatal day (PD) 4. AR mRNA in the BNSTp and AVPV of wild-type mice was not expressed on ED18 and emerged on PD4. In the AVPV, the aromatase mRNA level was higher on ED18, although the ERα mRNA level was higher on PD4 without any effect of AR gene deletion. Aromatase and ERα mRNA levels in the male BNSTp were significantly increased on PD4 by AR gene deletion. These results suggest that estradiol signaling via ERα during the perinatal period and testosterone signaling via AR during the postnatal period are required for masculinization of the BNSTp, whereas the former is sufficient to defeminize the AVPV.

  2. Regional Difference in Sex Steroid Action on Formation of Morphological Sex Differences in the Anteroventral Periventricular Nucleus and Principal Nucleus of the Bed Nucleus of the Stria Terminalis

    PubMed Central

    Kanaya, Moeko; Tsuda, Mumeko C.; Sagoshi, Shoko; Nagata, Kazuyo; Morimoto, Chihiro; Tha Thu, Chaw Kyi; Toda, Katsumi; Kato, Shigeaki; Ogawa, Sonoko; Tsukahara, Shinji

    2014-01-01

    Sex steroid action is critical to form sexually dimorphic nuclei, although it is not fully understood. We previously reported that masculinization of the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), which is larger and has more neurons in males than in females, involves aromatized testosterone that acts via estrogen receptor-α (ERα), but not estrogen receptor-β (ERβ). Here, we examined sex steroid action on the formation of the anteroventral periventricular nucleus (AVPV) that is larger and has more neurons in females. Morphometrical analysis of transgenic mice lacking aromatase, ERα, or ERβ genes revealed that the volume and neuron number of the male AVPV were significantly increased by deletion of aromatase and ERα genes, but not the ERβ gene. We further examined the AVPV and BNSTp of androgen receptor knockout (ARKO) mice. The volume and neuron number of the male BNSTp were smaller in ARKO mice than those in wild-type mice, while no significant effect of ARKO was found on the AVPV and female BNSTp. We also examined aromatase, ERα, and AR mRNA levels in the AVPV and BNSTp of wild-type and ARKO mice on embryonic day (ED) 18 and postnatal day (PD) 4. AR mRNA in the BNSTp and AVPV of wild-type mice was not expressed on ED18 and emerged on PD4. In the AVPV, the aromatase mRNA level was higher on ED18, although the ERα mRNA level was higher on PD4 without any effect of AR gene deletion. Aromatase and ERα mRNA levels in the male BNSTp were significantly increased on PD4 by AR gene deletion. These results suggest that estradiol signaling via ERα during the perinatal period and testosterone signaling via AR during the postnatal period are required for masculinization of the BNSTp, whereas the former is sufficient to defeminize the AVPV. PMID:25398007

  3. Early effects of gonadal steroids on the neuron number in the medial posterior region and the lateral division of the bed nucleus of the stria terminalis in the rat.

    PubMed

    Guillamón, A; Segovia, S; del Abril, A

    1988-12-01

    This work investigates the possible existence of sex differences in the number of neurons in the medial posterior region (BNSTMp) and the lateral division (BNSTL) of the bed nucleus of the stria terminalis in the rat. These two zones of the bed nucleus of the stria terminalis belong, respectively, to the vomeronasal system (VNS), and to the main olfactory system (MOS). In the BNSTMp, males showed a greater number of neurons than females. Early postnatal (Day 1 after birth) orchidectomy in males, and androgenization in females, eliminated and reversed these differences. In the BNSTL, sexual dimorphism was restricted to its anterior region (BNSTLa). Females showed there a greater number of neurons than males. Male orchidectomy on Day 1 after birth increased the number of neurons, while female androgenization produced the opposite effect. The results obtained in this study support the hypothesis that the VNS is sexodimorphic, and suggest that sex differences exist in MOS, and that these differences are controlled by gonadal steroids during the perinatal period.

  4. GluN2B-containing NMDA receptors blockade rescues bidirectional synaptic plasticity in the bed nucleus of the stria terminalis of cocaine self-administering rats.

    PubMed

    deBacker, Julian; Hawken, Emily R; Normandeau, Catherine P; Jones, Andrea A; Di Prospero, Cynthia; Mechefske, Elysia; Gardner Gregory, James; Hayton, Scott J; Dumont, Éric C

    2015-01-01

    Drugs of abuse have detrimental effects on homeostatic synaptic plasticity in the motivational brain network. Bidirectional plasticity at excitatory synapses helps keep neural circuits within a functional range to allow for behavioral flexibility. Therefore, impaired bidirectional plasticity of excitatory synapses may contribute to the behavioral hallmarks of addiction, yet this relationship remains unclear. Here we tracked excitatory synaptic strength in the oval bed nucleus of the stria terminalis (ovBNST) using whole-cell voltage-clamp recordings in brain slices from rats self-administering sucrose or cocaine. In the cocaine group, we measured both a persistent increase in AMPA to NMDA ratio (A:N) and slow decay time of NMDA currents throughout the self-administration period and after withdrawal from cocaine. In contrast, the sucrose group exhibited an early increase in A:N ratios (acquisition) that returned toward baseline values with continued self-administration (maintenance) and after withdrawal. The sucrose rats also displayed a decrease in NMDA current decay time with continued self-administration (maintenance), which normalized after withdrawal. Cocaine self-administering rats exhibited impairment in NMDA-dependent long-term depression (LTD) that could be rescued by GluN2B-containing NMDA receptor blockade. Sucrose self-administering rats demonstrated no impairment in NMDA-dependent LTD. During the maintenance period of self-administration, in vivo (daily intraperitoneally for 5 days) pharmacologic blockade of GluN2B-containing NMDA receptors did not reduce lever pressing for cocaine. However, in vivo GluN2B blockade did normalize A:N ratios in cocaine self-administrating rats, and dissociated the magnitude of ovBNST A:N ratios from drug-seeking behavior after protracted withdrawal. Altogether, our data demonstrate when and how bidirectional plasticity at ovBNST excitatory synapses becomes dysfunctional with cocaine self-administration and that NMDA

  5. The bed nucleus of the stria terminalis in the Syrian hamster (Mesocricetus auratus): absence of vasopressin expression in standard and wild-derived hamsters and galanin regulation by seasonal changes in circulating sex steroids.

    PubMed

    Bolborea, M; Ansel, L; Weinert, D; Steinlechner, S; Pévet, P; Klosen, P

    2010-02-03

    The bed nucleus of the stria terminalis (BNST) is a nucleus of the forebrain highly sensitive to sex steroids and containing vasopressin neurons implicated in several social- and reproduction-related behaviours such as scent-marking, aggression, pair bonding and parental behaviour. Sexually dimorphic vasopressin expression in BNST neurons has been reported in almost all rodents, with the notable exception of the Syrian hamster. In this species, vasopressin expression is completely absent in the BNST. Because almost all Syrian hamsters used in research are derived from a very small breeding stock captured in 1930, we compared commercially available Syrian hamsters with a recently captured, wild-derived breeding stock. We checked for vasopressin expression using in situ hybridization and immunohistochemistry. Vasopressin expression in BNST neurons was completely absent in both breeding stocks, confirming the absence of BNST vasopressin expression in Mesocricetus auratus and ruling out a breeding artefact. Because vasopressin expression in BNST neurons appears to be strictly dependent on circulating sex steroids, the absence of vasopressin expression in Syrian hamster BNST neurons might be due to an insensitivity of these neurons to sex steroids. BNST vasopressin neurons also express galanin. Although galanin expression in the BNST is not sexually dimorphic in the Syrian hamster, it appears to be regulated by sex steroids. In the Djungarian hamster, photoperiodically driven seasonal variations of circulating sex steroids result in a seasonal rhythm of galanin expression in BNST neurons. We analysed the sex steroid dependence of galanin expression in the Syrian hamster. Castration and short photoperiod-induced sexual quiescence both resulted in downregulation of galanin mRNA in cell bodies (BNST) and immunoreactivity in the fibres (lateral septum). Testosterone supplementation of short photoperiod-adapted animals was able to restore galanin expression. Thus Syrian

  6. Excitotoxic lesions of the bed nucleus of the stria terminalis (BNST) attenuate the effects of repeated stress on weight gain: evidence for the recruitment of BNST activity by repeated, but not acute, stress.

    PubMed

    Roman, Carolyn W; Lezak, Kimberly R; Kocho-Schellenberg, Margaret; Garret, Mark A; Braas, Karen; May, Victor; Hammack, Sayamwong E

    2012-02-01

    Exposure to repeated stress can lead to diverse and widespread behavioral consequences, including reduction in food and water intake and subsequent diminution in weight gain. Many reports have suggested that repeated stress substantially alters the neurochemistry, morphology and physiology of neurons within the bed nucleus of the stria terminalis (BNST). Here we investigate the role of the BNST in mediating the reduced weight gain observed during repeated stress. Rats exposed to a one-week variate stress paradigm exhibited a reduction in weight gain over the course of the 7-day paradigm. Excitotoxic lesions to a subregion of the anterolateral BNST containing the oval nucleus had no effects early in the 7-day paradigm, but significantly attenuated the effects of repeated stress on weight gain by the last day of stress. These data suggest that at least two mechanisms mediate the effects of stress on body weight gain, and that when stressor exposure becomes repeated, the BNST is recruited, worsening the symptoms of stressor exposure.

  7. Excitotoxic lesions of the bed nucleus of the stria terminalis (BNST) attenuate the effects of repeated stress on weight gain: Evidence for the recruitment of BNST activity by repeated, but not acute, stress

    PubMed Central

    Roman, Carolyn; Lezak, Kimberly R.; Kocho-Schellenberg, Margaret; Garret, Mark; Braas, Karen; May, Victor; Hammack, Sayamwong E.

    2011-01-01

    Exposure to repeated stress can lead to diverse and widespread behavioral consequences, including reduction in food and water intake and subsequent diminution in weight gain. Many reports have suggested that repeated stress substantially alters the neurochemistry, morphology and physiology of neurons within the bed nucleus of the stria terminalis (BNST). Here we investigate the role of the BNST in mediating the reduced weight gain observed during repeated stress. Rats exposed to a one-week variate stress paradigm exhibited a reduction in weight gain over the course of the 7 day paradigm. Excitotoxic lesions to a subregion of the anterolateral BNST containing the oval nucleus had no effects early in the 7 day paradigm, but significantly attenuated the effects of repeated stress on weight gain by the last day of stress. These data suggest that at least two mechanisms mediate the effects of stress on body weight gain, and that when stressor exposure becomes repeated, the BNST is recruited, worsening the symptoms of stressor exposure. PMID:22101300

  8. Lesions of the posterior bed nucleus of the stria terminalis eliminate opposite-sex odor preference and delay copulation in male Syrian hamsters: role of odor volatility and sexual experience

    PubMed Central

    Been, Laura E.; Petrulis, Aras

    2010-01-01

    In Syrian hamsters (Mesocricetus auratus), the expression of reproductive behavior requires the perception of social odors. The behavioral response to these odors is mediated by a network of ventral forebrain nuclei, including the posterior bed nucleus of the stria terminalis (pBNST). Previous studies have tested the role of pBNST in reproductive behavior, but the use of large, fiber-damaging lesions in these studies make it difficult to attribute post-lesion deficits to pBNST specifically. Thus, the current study used discrete, excitotoxic lesions of pBNST to test the role of pBNST in opposite-sex odor preference and copulatory behavior in both sexually-naïve and sexually-experienced males. Lesions of pBNST decreased sexually-naïve males’ investigation of volatile female odors, resulting in an elimination of opposite-sex odor preference. This elimination of preference was not due to a sensory deficit, as males with pBNST lesions were able to discriminate between odors. When, however, subjects were given sexual experience prior to pBNST lesions, their preference for volatile opposite-sex odors remained intact post-lesion. Similarly, when sexually-naïve or sexually-experienced subjects were allowed to contact the social odors during the preference test, lesions of pBNST decreased males’ investigation of female odors, but did not eliminate preference for opposite-sex odors, regardless of sexual experience. Finally, lesions of pBNST delayed the copulatory sequence in sexually-naïve, but not sexually-experienced, males such that they took longer to mount, intromit, ejaculate, and display long intromissions. Together, these results demonstrate that pBNST plays a unique and critical role in both appetitive and consummatory aspects of male reproductive behaviors. PMID:20597978

  9. Roles for pituitary adenylate cyclase-activating peptide (PACAP) expression and signaling in the bed nucleus of the stria terminalis (BNST) in mediating the behavioral consequences of chronic stress.

    PubMed

    Hammack, Sayamwong E; Roman, Carolyn W; Lezak, Kimberly R; Kocho-Shellenberg, Margaret; Grimmig, Bethany; Falls, William A; Braas, Karen; May, Victor

    2010-11-01

    Anxiety disorders are frequently long-lasting and debilitating for more than 40 million American adults. Although stressor exposure plays an important role in the etiology of some anxiety disorders, the mechanisms by which exposure to stressful stimuli alters central circuits that mediate anxiety-like emotional behavior are still unknown. Substantial evidence has implicated regions of the central extended amygdala, including the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala as critical structures mediating fear- and anxiety-like behavior in both humans and animals. These areas organize coordinated fear- and anxiety-like behavioral responses as well as peripheral stress responding to threats via direct and indirect projections to the paraventricular nucleus of the hypothalamus and brainstem regions (Walker et al. Eur J Pharmacol 463:199-216, 2003, Prog Neuropsychopharmacol Biol Psychiatry 33(8):1291-1308, 2009; Ulrich-Lai and Herman Nat Rev Neurosci 10:397-409, 2009). In particular, the BNST has been argued to mediate these central and peripheral responses when the perceived threat is of long duration (Waddell et al. Behav Neurosci 120:324-336, 2006) and/or when the anxiety-like response is sustained (Walker and Davis Brain Struct Funct 213:29-42, 2008); hence, the BNST may mediate pathological anxiety-like states that result from exposure to chronic stress. Indeed, chronic stress paradigms result in enhanced BNST neuroplasticity that has been associated with pathological anxiety-like states (Vyas et al. Brain Res 965:290-294, 2003; Pego et al. Eur J Neurosci 27:1503-1516, 2008). Here we review evidence that suggests that pituitary adenylate cyclase-activating polypeptide (PACAP) and corticotropin-releasing hormone (CRH) work together to modulate BNST function and increase anxiety-like behavior. Moreover, we have shown that BNST PACAP as well as its cognate PAC1 receptor is substantially upregulated following chronic stress

  10. The Slowly Enlarging Ventriculus Terminalis

    PubMed Central

    Woodley-Cook, Joel; Konieczny, Magdalena; Spears, Julian

    2016-01-01

    Summary Background A cerebral spinal fluid (CSF) cavity within the conus medullaris has been described by the term ventriculus terminalis (VT) or the fifth ventricle. The finding of a VT on MRI imaging of the lumbar spine is often incidental but may be found in patients with low back pain or neuromuscular deficits. These lesions, when identified, are thought to regress or remain stable in terms of size, although some have been described to enlarge in the presence of post-traumatic meningeal hemorrhages or deformities of the vertebral canal. Case Report We describe a case of a slowly growing VT in a patient with progressing lower limb weakness without any history or imaging findings of trauma or spinal canal abnormalities. Conclusions We present an intriguing case of a slowly growing VT in a woman with progressive neurological symptoms. Surgical fenestration provided complete symptomatic relief and follow-up imaging two years after surgery demonstrated no evidence of recurrence. This, to our knowledge, is the first described case of a slowly enlarging VT independent of any other imaging findings. PMID:27867442

  11. Evaluating the stria content in optical glasses

    NASA Astrophysics Data System (ADS)

    Doladugina, V. S.

    2004-12-01

    This paper discusses previously unpublished results of a large collaborative project carried out by Russian and German specialists on the study of the stria content of glasses with the purpose of estimating the possibility of creating a unified standard corresponding to world requirements. A comparison of the techniques existing in the USSR and the German Democratic Republic in 1981-82 in the form of GOST [State Standard] 3521-82 and TGL 21790 did not lead to a positive result, and it was impossible to create a unified document on the evaluation and monitoring of the stria content of uncolored optical glasses. The causes of the situation thus created are explained, and possible ways of solving this problem are considered.

  12. Intense pulsed light hair removal in a patient with congenital hypertrichosis terminalis.

    PubMed

    Attia, Abeer; El Noury, Amr; Abd Alhafez, Mamdouh

    2012-01-01

    We report a case of 1-year-old girl with congenital hypertrichosis terminalis treated using intense pulsed light for hair removal. Repeated sessions were performed every 3 weeks. Facial hair reduction was achieved after 12 sessions and body hair reduction after 15 sessions. Intense pulsed light resulted in 75% reduction of hair in congenital hypertrichosis terminalis.

  13. Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

    PubMed Central

    Liu, Huizhan; Li, Yi; Chen, Lei; Zhang, Qian; Pan, Ning; Nichols, David H.; Zhang, Weiping J.; Fritzsch, Bernd

    2016-01-01

    Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria. We showed that stria morphology and EP remained normal for long time despite a complete loss of all hair cells. We then used a mouse model that has an abnormal stria morphology and function due to mutation of the Mitf gene to determine whether hair cells are able to survive and transduce sound signals without a normal electrochemical environment in the endolymph. A strial defect, reflected by missing intermediate cells in the stria and by reduction of EP, led to systematic outer hair cell death from the base to the apex after postnatal day 18. However, an 18-mV EP was sufficient for outer hair cell survival. Surprisingly, inner hair cell survival was less vulnerable to reduction of the EP. Our studies show that normal function of the stria is essential for adult outer hair cell survival, while the survival and normal function of the stria vascularis do not depend on functional hair cells. PMID:28030585

  14. [Neuronal mechanisms underlying pain-induced negative emotions].

    PubMed

    Minami, Masabumi

    2012-11-01

    Pain consists of sensory-discriminative and negative emotional components. Although the neuronal basis of the sensory component of pain has been studied extensively, the neuronal mechanisms underlying the negative emotional component are not well understood. Recently, behavioral studies using a conditioned place paradigm have successfully elucidated the neuronal circuits and mechanisms underlying the negative emotional component of pain. Excitotoxic lesions of the anterior cingulate cortex (ACC), central amygdaloid nucleus, basolateral amygdaloid nucleus (BLA), or bed nucleus of the stria terminalis (BNST) suppress intraplantar formalin-induced aversive responses. Glutamatergic transmission within the ACC and BLA via N-methyl-D-asparate (NMDA) receptors has been shown to play a critical role in these aversive responses. In the BNST, especially its ventral part, noradrenergic transmission via β-adrenergic receptors has been shown to be important for pain-induced aversion. Because persistent pain is frequently associated with psychological and emotional dysfunctions, studies on the neuronal circuits and molecular mechanisms involved in the negative emotional component of pain may have considerable clinical importance in the treatment of chronic pain. Here, I have reviewed behavioral studies investigating the neuronal mechanisms underlying the negative emotional component of pain and have introduced our data showing the pivotal role of amygdala and BNST in pain-induced aversion.

  15. Distribution and Functional Expression of Kv4 Family α Subunits and Associated KChIP β Subunits in the Bed Nucleus of the Stria Terminalis

    PubMed Central

    Rainnie, Donald G.; Hazra, Rimi; Dabrowska, Joanna; Guo, Ji-Dong; Li, Chen Chen; Dewitt, Sarah; Muly, E. Chris

    2014-01-01

    Regulation of BNSTALG neuronal firing activity is tightly regulated by the opposing actions of the fast outward potassium current, IA, mediated by α subunits of the Kv4 family of ion channels, and the transient inward calcium current, IT. Together, these channels play a critical role in regulating the latency to action potential onset, duration, and frequency, as well as dendritic back-propagation and synaptic plasticity. Previously we have shown that Type I–III BNSTALG neurons express mRNA transcripts for each of the Kv4 α subunits. However, the biophysical properties of native IA channels are critically dependent on the formation of macromolecular complexes of Kv4 channels with a family of chaperone proteins, the potassium channel-interacting proteins (KChIP1–4). Here we used a multidisciplinary approach to investigate the expression and function of Kv4 channels and KChIPs in neurons of the rat BNSTALG. Using immunofluorescence we demonstrated the pattern of localization of Kv4.2, Kv4.3, and KChIP1–4 proteins in the BNSTALG. Moreover, our single-cell reverse-transcription polymerase chain reaction (scRT-PCR) studies revealed that mRNA transcripts for Kv4.2, Kv4.3, and all four KChIPs were differentially expressed in Type I–III BNSTALG neurons. Furthermore, immunoelectron microscopy revealed that Kv4.2 and Kv4.3 channels were primarily localized to the dendrites and spines of BNSTALG neurons, and are thus ideally situated to modulate synaptic transmission. Consistent with this observation, in vitro patch clamp recordings showed that reducing postsynaptic IA in these neurons lowered the threshold for long-term potentiation (LTP) induction. These results are discussed in relation to potential modulation of IA channels by chronic stress. PMID:24037673

  16. Subfrontal trans-lamina terminalis approach to a third ventricular craniopharyngioma.

    PubMed

    Choudhri, Omar; Chang, Steven D

    2016-01-01

    Craniopharyngiomas are benign, partly cystic epithelial tumors that can rarely occur in a retrochiasmatic location with involvement of the third ventricle. The lamina terminalis is an important neurosurgical corridor to these craniopharyngiomas in the anterior portion of the third ventricle. We present a video case of a large midline suprasellar and third ventricular craniopharyngioma in a 32-year-old male with visual disturbances. The tumor was approached with a subfrontal translamina terminalis exposure, and a gross-total resection of the tumor was achieved. This surgery involved working through a lamina terminalis fenestration around the optic nerve, optic chiasm, optic tracts, and the anterior communicating artery complex. This video illustrates the techniques employed in performing a transbasal anterior skull base approach to the third ventricle and demonstrates vivid surgical anatomy of neurovascular structures around the lamina terminalis. The video can be found here: https://youtu.be/fCYMgx8SnKs .

  17. Ethanol-induced alterations of c-Fos immunoreactivity in specific limbic brain regions following ethanol discrimination training.

    PubMed

    Besheer, Joyce; Schroeder, Jason P; Stevenson, Rebekah A; Hodge, Clyde W

    2008-09-26

    The discriminative stimulus properties of ethanol are functionally regulated by ionotropic GABA(A) and NMDA receptors in specific limbic brain regions including the nucleus accumbens, amygdala, and hippocampus, as determined by microinjection studies. The purpose of the present work was to further investigate potential neural substrates of ethanol's discriminative stimulus effects by examining if ethanol discrimination learning produces changes in brain regional response to ethanol. To accomplish this goal, immunohistochemistry was used to assess the effects of ethanol (2 g/kg) on c-Fos immunoreactivity (Fos-IR). Comparisons in ethanol-induced Fos-IR were made between a group of rats that was trained to discriminate the stimulus properties of ethanol (2 g/kg, IG) from water (IG) and a drug/behavior-matched control group that did not receive differential reinforcement for lever selection, which precluded acquisition of discriminative stimulus control by ethanol. In some brain regions discrimination training had no effect on ethanol-induced Fos-IR changes (caudate putamen, bed nucleus of the stria terminalis, and CA1 region of the hippocampus). In contrast, discrimination training altered the pattern of ethanol-induced Fos-IR in the nucleus accumbens (core), medial septum, and the hippocampus (dentate and CA3). These results indicate that having behavior under the stimulus control of ethanol can change ethanol-induced Fos-IR in some brain regions. This suggests that learning about the subjective properties of ethanol produces adaptive changes in how the brain responds to acute ethanol exposure.

  18. The hallucinogen d-lysergic acid diethylamide (d-LSD) induces the immediate-early gene c-Fos in rat forebrain.

    PubMed

    Frankel, Paul S; Cunningham, Kathryn A

    2002-12-27

    The hallucinogen d-lysergic acid diethylamide (d-LSD) evokes dramatic somatic and psychological effects. In order to analyze the neural activation induced by this unique psychoactive drug, we tested the hypothesis that expression of the immediate-early gene product c-Fos is induced in specific regions of the rat forebrain by a relatively low, behaviorally active, dose of d-LSD (0.16 mg/kg, i.p.); c-Fos protein expression was assessed at 30 min, and 1, 2 and 4 h following d-LSD injection. A time- and region-dependent expression of c-Fos was observed with a significant increase (P<0.05) in the number of c-Fos-positive cells detected in the anterior cingulate cortex at 1 h, the shell of the nucleus accumbens at 1 and 2 h, the bed nucleus of stria terminalis lateral at 2 h and the paraventricular hypothalamic nucleus at 1, 2 and 4 h following systemic d-LSD administration. These data demonstrate a unique pattern of c-Fos expression in the rat forebrain following a relatively low dose of d-LSD and suggest that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD.

  19. Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

    PubMed Central

    Mantsch, John R; Baker, David A; Funk, Douglas; Lê, Anh D; Shaham, Yavin

    2016-01-01

    In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse. PMID:25976297

  20. Adolescent nicotine induces persisting changes in development of neural connectivity.

    PubMed

    Smith, Robert F; McDonald, Craig G; Bergstrom, Hadley C; Ehlinger, Daniel G; Brielmaier, Jennifer M

    2015-08-01

    Adolescent nicotine induces persisting changes in development of neural connectivity. A large number of brain changes occur during adolescence as the CNS matures. These changes suggest that the adolescent brain may still be susceptible to developmental alterations by substances which impact its growth. Here we review recent studies on adolescent nicotine which show that the adolescent brain is differentially sensitive to nicotine-induced alterations in dendritic elaboration, in several brain areas associated with processing reinforcement and emotion, specifically including nucleus accumbens, medial prefrontal cortex, basolateral amygdala, bed nucleus of the stria terminalis, and dentate gyrus. Both sensitivity to nicotine, and specific areas responding to nicotine, differ between adolescent and adult rats, and dendritic changes in response to adolescent nicotine persist into adulthood. Areas sensitive to, and not sensitive to, structural remodeling induced by adolescent nicotine suggest that the remodeling generally corresponds to the extended amygdala. Evidence suggests that dendritic remodeling is accompanied by persisting changes in synaptic connectivity. Modeling, electrophysiological, neurochemical, and behavioral data are consistent with the implication of our anatomical studies showing that adolescent nicotine induces persisting changes in neural connectivity. Emerging data thus suggest that early adolescence is a period when nicotine consumption, presumably mediated by nicotine-elicited changes in patterns of synaptic activity, can sculpt late brain development, with consequent effects on synaptic interconnection patterns and behavior regulation. Adolescent nicotine may induce a more addiction-prone phenotype, and the structures altered by nicotine also subserve some emotional and cognitive functions, which may also be altered. We suggest that dendritic elaboration and associated changes are mediated by activity-dependent synaptogenesis, acting in part

  1. Neurokinin-1 receptor antagonism attenuates neuronal activity triggered by stress-induced reinstatement of alcohol seeking

    PubMed Central

    Schank, J.R.; Nelson, B.S.; Damadzic, R.; Tapocik, J.D.; Yao, M.; King, C.E.; Rowe, K.E.; Cheng, K.; Rice, K.C.; Heilig, M.

    2015-01-01

    Substance P (SP) and its cognate neurokinin-1 receptor (NK1R) are involved in alcohol-related behaviors. We have previously reported that NK1R antagonism attenuates stress-induced reinstatement of alcohol seeking and suppresses escalated alcohol self-administration, but does not affect primary reinforcement or cue-induced reinstatement. Here, we administered an NK1R antagonist or vehicle prior to footshock-induced reinstatement of alcohol seeking, and mapped the resulting neuronal activation using Fos immunohistochemistry. As expected, vehicle treated animals exposed to footshock showed induction of Fos immunoreactivity in several regions of the brain stress circuitry, including the amygdala (AMG), nucleus accumbens (NAC), dorsal raphe nucleus (DR), prefrontal cortex (PFC), and bed nucleus of the stria terminalis (BNST). NK1R antagonism selectively suppressed the stress-induced increase in Fos in the DR and NAC shell. In the DR, Fos-induction by stress largely overlapped with tryptophan hydroxylase (TrpH), indicating activation of serotonergic neurons. Of NAC shell neurons activated during stress-induced reinstatement of alcohol seeking, about 30% co-expressed dynorphin (DYN), while 70% co-expressed enkephalin (ENK). Few (<1%) activated NAC shell neurons co-expressed choline acetyltransferase (ChAT), which labels the cholinergic interneurons of this region. Infusion of the NK1R antagonist L822429 into the NAC shell blocked stress-induced reinstatement of alcohol seeking. In contrast, L822429 infusion into the DR had no effect, suggesting that the influence of NK1R signaling on neuronal activity in the DR is indirect. Taken together, our results outline a potential pathway through which endogenous NK1R activation mediates stress-induced alcohol seeking. PMID:26188146

  2. Calretinin and FMRFamide immunoreactivity in the nervus terminalis of prenatal tree shrews (Tupaia belangeri).

    PubMed

    Malz, Cordula Renate; Kuhn, Hans-Jürg

    2002-04-30

    The distribution and development of FMRFamide- and calretinin-immunoreactive neurons were investigated in the nervus terminalis of prenatal tree shrews from gestation day 19 onwards. The first FMRFamide-immunoreactive cells were observed medially in the olfactory epithelium on gestation day 20. From gestation day 23 onwards, the migrating nervus terminalis ganglion cells showed FMRFamide calretinin immunoreactivity. The distribution pattern of FMRFamide- and calretinin-immunoreactive cells was similar along the migratory route and in the ganglion of the terminal nerve. However, most probably calretinin and FMRFamide were expressed in separate neuronal populations. For the first time in a mammal, FMRFamide and calretinin are reported to occur in the migrating perikarya and neuronal processes of the nervus terminalis during prenatal development. The results suggest (i) an early activation of the rostral FMRFamide-immunoreactive migratory stream comparable to that described for the GnRH-immunoreactive part of the terminal nerve in other mammals and possibly (ii) an involvement of calretinin in mechanisms of cell migration and outgrowth of neuronal processes in the terminal nerve during the studied period.

  3. The neural background of hyper-emotional aggression induced by post-weaning social isolation.

    PubMed

    Toth, Mate; Tulogdi, Aron; Biro, Laszlo; Soros, Petra; Mikics, Eva; Haller, Jozsef

    2012-07-15

    Post-weaning social isolation in rats is believed to model symptoms of early social neglect-induced externalizing problems including aggression-related problems. We showed earlier that rats reared in social isolation were hyper-aroused during aggressive contacts, delivered substantially more attacks that were poorly signaled and were preferentially aimed at vulnerable body parts of opponents (head, throat and belly). Here we studied the neural background of this type of aggression by assessing the expression of the activation marker c-Fos in 22 brain areas of male Wistar rats submitted to resident-intruder conflicts. Post-weaning social isolation readily produced the behavioral alterations noticed earlier. Social isolation significantly increased the activation of brain areas that are known to directly or indirectly control inter-male aggression. Particularly, the medial and lateral orbitofrontal cortices, anterior cingulate cortex, bed nucleus of the stria terminalis, medial and basolateral amygdala, hypothalamic attack area, hypothalamic paraventricular nucleus and locus coeruleus showed increased activations. This contrasts our earlier findings obtained in rats with experimentally induced hypoarousal, where abnormal attack patterns were associated with over-activated central amygdala, lateral hypothalamus, and ventrolateral periaqueductal gray that are believed to control predatory attacks. We have observed no similar activation patterns in rats socially isolated from weaning. In summary, these findings suggest that despite some phenotypic similarities, the neuronal background of hypo and hyperarousal-associated abnormal forms of aggression are markedly different. While the neuronal activation patterns induced by normal rivalry and hypoarousal-driven aggression are qualitative different, hyperarousal-associated aggression appears to be an exaggerated form of rivalry aggression.

  4. Site specific effects of anosmia and cloacal gland anesthesia on Fos expression induced in male quail brain by sexual behavior

    PubMed Central

    Taziaux, Mélanie; Keller, Matthieu; Ball, Gregory F.; Balthazart, Jacques

    2008-01-01

    In rats, expression of the immediate early gene, c-fos observed in the brain following male copulatory behavior relates mostly to the detection of olfactory information originating from the female and to somatosensory feedback from the penis. However, quail, like most birds, are generally considered to have a relatively poorly developed sense of smell. Furthermore, quail have no intromittent organ (e.g., penis). It is therefore intriguing that expression of male copulatory behavior induces in quail and rats a similar pattern of c-fos expression in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BSTM) and parts of the amygdala. We analyzed here by immunocytochemistry Fos expression in the mPOA/BSTM/amygdala of male quail that had been allowed to copulate with a female during standardized tests. Before these tests, some of the males had either their nostrils plugged, or their cloacal area anesthetized, or both. A control group was not exposed to females. These manipulations did not affect frequencies of male sexual behavior and all birds exposed to a female copulated normally. In the mPOA, the increased Fos expression induced by copulation was not affected by the cloacal gland anesthesia but was markedly reduced in subjects deprived of olfactory input. Both manipulations affected copulation-induced Fos expression in the BSTM. No change in Fos expression was observed in the amygdala. Thus immediate early gene expression in the mPOA and BSTM of quail is modulated at least in part by olfactory cues and/or somatosensory stimuli originating from the cloacal gland. Future work should specify the nature of these stimuli and their function in the expression of avian male sexual behavior. PMID:18638505

  5. Nitric oxide synthase-cyclo-oxygenase pathways in organum vasculosum laminae terminalis: possible role in pyrogenic fever in rabbits.

    PubMed Central

    Lin, J. H.; Lin, M. T.

    1996-01-01

    1. Fever was induced in rabbits by administration of Escherichia coli endotoxin (lipopolysaccharide; LPS; 0.001-10 micrograms) into the organum vasculosum laminae terminalis (OVLT). Deep body temperature was evaluated over a period of 7 h. 2. The LPS-induced febrile response was mimicked by intra-OVLT injection of the nitric oxide (NO) donors, S-nitroso-acetylpenicillamine (SNAP, 1-10 micrograms), sodium nitroprusside (SNP, 50 micrograms), or hydroxylamine (10 micrograms), the cyclic GMP analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP, 10-100 micrograms), or prostaglandin E2 (PGE2, 0.2 micrograms). 3. Dexamethasone (Dex, a potent inhibitor of the transcription of inducible NO synthase, iNOS, 10 micrograms), anisomycin (a protein synthesis inhibitor, 100 micrograms), L-N5-(1-iminoethyl)ornithine (L-NIO; an irreversible NOS inhibitor, 10-200 micrograms), aminoguanidine (a specific iNOS inhibitor, 1000 micrograms), or NG-methyl-L-arginine acetate (L-NMMA, a NOS inhibitor, 100 micrograms) inhibited fever induced by LPS when injected into the OVLT 1 h before LPS injection. An intra-OVLT dose of 1000 micrograms of NG-nitro-L-arginine methyl ester (L-NAME, a potent inhibitor of constitutive NOS) did not exhibit antipyretic effects. 4. Methylene blue (an inhibitor of NOS and soluble guanylate cyclase, 1-10 micrograms), 6-(phenylamino)-5,8-quinolinedione (LY-83583; an inhibitor of soluble guanylate cyclase and NO release, 20 micrograms), or indomethacin (an inhibitor of cyclo-oxygenase, COX, 400 micrograms) inhibited fever induced by LPS when injected into the OVLT 1 h before LPS injection. Pretreatment with methylene blue or haemoglobin (a NO scavenger, 100 micrograms) attenuated the fever induced by intra-OVLT injection of SNAP. 5. The PGE2-induced fever was potentiated, rather then attenuated, by pretreatment with an intra-OVLT dose of animoguanidine (1000 micrograms), L-NMMA (100 micrograms) or L-NIO (200 micrograms). 6. These results suggest that iNOS-COX pathways in the

  6. Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain.

    PubMed

    Valjent, Emmanuel; Pagès, Christiane; Hervé, Denis; Girault, Jean-Antoine; Caboche, Jocelyne

    2004-04-01

    A major goal of research on addiction is to identify the molecular mechanisms of long-lasting behavioural alterations induced by drugs of abuse. Cocaine and delta-9-tetrahydrocannabinol (THC) activate extracellular signal-regulated kinase (ERK) in the striatum and blockade of the ERK pathway prevents establishment of conditioned place preference to these drugs. However, it is not known whether activation of ERK in the striatum is specific for these two drugs and/or this brain region. We studied the appearance of phospho-ERK immunoreactive neurons in CD-1 mouse brain following acute administration of drugs commonly abused by humans, cocaine, morphine, nicotine and THC, or of other psychoactive compounds including caffeine, scopolamine, antidepressants and antipsychotics. Each drug generated a distinct regional pattern of ERK activation. All drugs of abuse increased ERK phosphorylation in nucleus accumbens, lateral bed nucleus of the stria terminalis, central amygdala and deep layers of prefrontal cortex, through a dopamine D1 receptor-dependent mechanism. Although some non-addictive drugs moderately activated ERK in a few of these areas, they never induced this combined pattern of strong activation. Antidepressants and caffeine activated ERK in hippocampus and cerebral cortex. Typical antipsychotics mildly activated ERK in dorsal striatum and superficial prefrontal cortex, whereas clozapine had no effect in the striatum, but more widespread effects in cortex and amygdala. Our results outline a subset of structures in which ERK activation might specifically contribute to the long-term effects of drugs of abuse, and suggest mapping ERK activation in brain as a way to identify potential sites of action of psychoactive drugs.

  7. Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

    PubMed

    Gaykema, Ronald P A; Goehler, Lisa E

    2011-03-01

    Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from

  8. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism

    PubMed Central

    Klampfl, Stefanie M.; Brunton, Paula J.; Bayerl, Doris S.; Bosch, Oliver J.

    2016-01-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5 h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum. PMID:26630389

  9. Brain regions influenced by the lateral parabrachial nucleus in angiotensin II-induced water intake.

    PubMed

    Davern, P J; McKinley, M J

    2013-11-12

    This study examined which brain regions are influenced by an inhibitory lateral parabrachial nucleus (LPBN) mechanism that affects water intake. Controls and rats with bilateral LPBN lesions were administered angiotensin II (AngII) (0.5mg/kg subcutaneous - SC), drinking responses measured, and brains processed for Fos-immunohistochemistry. A separate group of LPBN-lesioned and non-lesioned animals were denied water for 90 min prior to perfusion to remove any confounding factor of water intake. LPBN-lesioned rats drank a cumulative volume of 9 mL compared with <4 mL by controls (p<0.01). Compared with sham-lesioned animals, Fos expression was attenuated in overdrinking LPBN-lesioned rats in the median preoptic nucleus (MnPO), paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON) (p<0.001), bed nucleus of the stria terminalis and central nucleus of the amygdala (p<0.01). In LPBN-lesioned rats that did not drink, greater numbers of activated neurons were detected in the PVN (p<0.001), SON (p<0.01), MnPO, nucleus of the solitary tract (NTS) and area postrema (p<0.05) in response to SC AngII, compared with non-lesioned rats. These data suggest that the direct effects of LPBN lesions caused an increase in AngII-induced water intake and in rats that did not drink an increase in Fos expression, while indirect secondary effects of LPBN lesions caused a reduction in Fos expression possibly related to excessive ingestion of water. An inhibitory mechanism, likely related to arterial baroreceptor stimulation, relayed by neurons located in the LPBN influences the responses of the MnPO, PVN and SON to increases in peripheral AngII.

  10. Neural correlates underlying naloxone-induced amelioration of sexual behavior deterioration due to an alarm pheromone

    PubMed Central

    Kobayashi, Tatsuya; Kiyokawa, Yasushi; Takeuchi, Yukari; Mori, Yuji

    2015-01-01

    Sexual behavior is suppressed by various types of stressors. We previously demonstrated that an alarm pheromone released by stressed male Wistar rats is a stressor to other rats, increases the number of mounts needed for ejaculation, and decreases the hit rate (described as the number of intromissions/sum of the mounts and intromissions). This deterioration in sexual behavior was ameliorated by pretreatment with the opioid receptor antagonist naloxone. However, the neural mechanism underlying this remains to be elucidated. Here, we examined Fos expression in 31 brain regions of pheromone-exposed rats and naloxone-pretreated pheromone-exposed rats 60 min after 10 intromissions. As previously reported, the alarm pheromone increased the number of mounts and decreased the hit rate. In addition, Fos expression was increases in the anterior medial division (BNSTam), anterior lateral division (BNSTal) and posterior division (BNSTp) of the bed nucleus of the stria terminalis, parvocellular part of the paraventricular nucleus of the hypothalamus, arcuate nucleus, dorsolateral and ventrolateral periaqueductal gray, and nucleus paragigantocellularis (nPGi). Fos expression was decreased in the magnocellular part of the paraventricular nucleus of the hypothalamus. Pretreatment with naloxone blocked the pheromone-induced changes in Fos expression in the magnocellular part of the paraventricular nucleus of the hypothalamus, ventrolateral periaqueductal gray, and nPGi. Based on these results, we hypothesize that the alarm pheromone deteriorated sexual behavior by activating the ventrolateral periaqueductal gray-nucleus paragigantocellularis cluster and suppressing the magnocellular part of the paraventricular nucleus of the hypothalamus (PVN) via the opioidergic pathway. PMID:25755631

  11. Head anatomy of adult Sisyra terminalis (Insecta: Neuroptera: Sisyridae)--functional adaptations and phylogenetic implications.

    PubMed

    Randolf, Susanne; Zimmermann, Dominique; Aspöck, Ulrike

    2013-11-01

    The external and internal head anatomy of Sisyra terminalis is described in detail and compared with data from literature. A salivary pump consisting of a peculiar reservoir and a hitherto unknown muscle, M. ductus salivarii, is newly described for Neuroptera. The upward folded paraglossae form a secondary prolongation of the salivary system. These structures are discussed as functional adaptations for feeding on aphids and desiccated honeydew. In a phylogenetic analysis the basal position of the Sisyridae within Neuroptera is retrieved. The following new synapomorphies are postulated: (1) for Neuropterida, the presence of a M. submentomentalis and prepharyngeal ventral transverse muscles, and the absence of a M. submentopraementalis; (2) for Neuroptera and Sialidae, the presence of a mandibular gland; (3) for Neuroptera, the presence of four scapopedicellar muscles; (4) for Neuroptera exclusive Nevrorthidae and Sisyridae, the weakening of dorsal tentorial arms, the presence of a M. tentoriomandibularis medialis superior and the shifted origin of M. tentoriocardinalis.

  12. Functional correlates of activity in neurons projecting from the lamina terminalis to the ventrolateral periaqueductal gray

    PubMed Central

    Uschakov, Aaron; McGinty, Dennis; Szymusiak, Ronald; McKinley, Michael J.

    2010-01-01

    The lamina terminalis (LT) consists of the organum vasculosum of the lamina terminalis (OVLT) the median preoptic nucleus (MnPO) and the subfornical organ (SFO). All subdivisions of the LT project to the ventrolateral periaqueductal gray (vlPAG). The LT and the vlPAG are implicated in several homeostatic and behavioral functions including body fluid homeostasis, thermoregulation and the regulation of sleep and waking. By combining visualization of c-Fos protein and retrograde neuroanatomical tracer we have examined the functional correlates of LT-vlPAG projection neurons. Rats were injected with retrograde tracer into the vlPAG and following a one week recovery period, they were subjected to either, hypertonic saline administration (0.5M NaCl, 1ml/100g-i.p.), 24hrs water deprivation, isoproterenol administration (increases circulating AngII; 50μg/kg-s.c.), heat exposure (39°C for 60 mins) or permitted 180 minutes spontaneous sleep. Retrogradely labelled neurons from the vlPAG and double labelled neurons were then identified and quantified throughout the LT. OVLT-vlPAG projection neurons were most responsive to hypertonic saline and water deprivation. SFO-vlPAG projection neurons were most active following isoproterenol administration and MnPO-vlPAG projection neurons displayed significantly more Fos immunostaining following water deprivation, heat exposure and sleep. These results support the existence of functional subdivisions of LT-vlPAG projecting neurons and indicate three patterns of activity that correspond to thermal and sleep wake regulation, osmotic or hormonal stimuli. PMID:20092577

  13. Ventral Lamina Terminalis Mediates Enhanced Cardiovascular Responses of RVLM Neurons During Increased Dietary Salt

    PubMed Central

    Adams, Julye M.; Bardgett, Megan E.; Stocker, Sean D.

    2009-01-01

    Increased dietary salt enhances sympathoexcitatory and sympathoinhibitory responses evoked from the rostral ventrolateral medulla (RVLM). The purpose of the present study was to determine whether neurons of the forebrain lamina terminalis (LT) mediated these changes in the RVLM. Male Sprague-Dawley rats with and without LT lesions were fed normal chow and given access to water or 0.9% NaCl for 14-15 days. Unilateral injection of L-glutamate into the RVLM produced significantly larger increases in renal sympathetic nerve activity (SNA) and arterial blood pressure (ABP) of sham rats ingesting 0.9% NaCl versus water. However, these differences were not observed between ventral LT-lesioned rats drinking 0.9% NaCl versus water. Similar findings were observed when angiotensin II or GABA were injected into the RVLM. Interestingly, a subset of animals drinking 0.9% but with damage restricted to the organum vasculosum of the lamina terminalis did not show enhanced responses to L-glutamate or GABA. In marked contrast, RVLM injection of L-glutamate or GABA produced exaggerated SNA and ABP responses in animals drinking 0.9% NaCl versus water after an acute ventral LT lesion or chronic lesion of the subfornical organ. Additional experiments demonstrate plasma sodium concentration and osmolality were increased at night in rats ingesting 0.9% NaCl. These findings suggest that neurons of the ventral LT mediate the ability of increased dietary salt to enhance the responsiveness of RVLM sympathetic neurons. PMID:19506102

  14. ATP-containing vesicles in stria vascular marginal cell cytoplasms in neonatal rat cochlea are lysosomes

    PubMed Central

    Liu, Jun; Liu, Wenjing; Yang, Jun

    2016-01-01

    We confirmed that ATP is released from cochlear marginal cells in the stria vascular but the cell organelle in which ATP stores was not identified until now. Thus, we studied the ATP-containing cell organelles and suggest that these are lysosomes. Primary cultures of marginal cells of Sprague-Dawley rats aged 1–3 days was established. Vesicles within marginal cells stained with markers were identified under confocal laser scanning microscope and transmission electron microscope (TEM). Then ATP release from marginal cells was measured after glycyl-L-phenylalanine-ß- naphthylamide (GPN) treatment using a bioluminescent assay. Quinacrine-stained granules within marginal cells were labeled with LysoTracker, a lysosome tracer, and lysosomal-associated membrane protein 1(LAMP1), but not labeled with the mitochondrial tracer MitoTracker. Furthermore, LysoTracker-labelled puncta showed accumulation of Mant-ATP, an ATP analog. Treatment with 200 μM GPN quenched fluorescently labeled puncta after incubation with LysoTracker or quinacrine, but not MitoTracker. Quinacrine-labeled organelles observed by TEM were lysosomes, and an average 27.7 percent increase in ATP luminescence was observed in marginal cells extracellular fluid after GPN treatment. ATP-containing vesicles in cochlear marginal cells of the stria vascular from neonatal rats are likely lysosomes. ATP release from marginal cells may be via Ca2+-dependent lysosomal exocytosis. PMID:26864824

  15. Increased vasopressin expression in the BNST accompanies paternally induced territoriality in male and female California mouse offspring.

    PubMed

    Yohn, Christine N; Leithead, Amanda B; Becker, Elizabeth A

    2017-03-27

    While developmental consequences of parental investment on species-typical social behaviors has been extensively characterized in same-sex parent-offspring interactions, the impact of opposite-sex relationships is less clear. In the bi-parental California mouse (Peromyscus californicus), paternal retrieval behavior induces territorial aggression and the expression of arginine vasopressin (AVP) in adult male offspring. Although similar patterns of territorially emerge among females, the sexually dimorphic AVP system has not been considered since it is generally thought to regulate male-typical behavior. However, we recently demonstrated that male and female P. californicus offspring experience increases in plasma testosterone following paternal retrieval. Since AVP expression is androgen-dependent during development, we postulate that increases in AVP expression may accompany territoriality in female, as well as male offspring. To explore this aim, adult P. californicus offspring that received either high or low levels of paternal care (retrievals) during early development were tested for territoriality and immunohistochemical analysis of AVP within the bed nucleus of the stria terminalis (BNST), paraventricular nucleus (PVN), and supraoptic nucleus (SON). Consistent with previous studies, high care offspring were more aggressive than low care offspring. Moreover, high care offspring had significantly more AVP immunoreactive (AVP-ir) cells within the BNST than low care offspring. This pattern was observed within female as well as male offspring, suggesting an equally salient role for paternal care on female offspring physiology. Regardless of early social experience, sex differences in AVP persisted in the BNST, with males having greater expression than females.

  16. Mechanism generating endocochlear potential: role played by intermediate cells in stria vascularis.

    PubMed Central

    Takeuchi, S; Ando, M; Kakigi, A

    2000-01-01

    The endocochlear DC potential (EP) is generated by the stria vascularis, and essential for the normal function of hair cells. Intermediate cells are melanocytes in the stria vascularis. To examine the contribution of the membrane potential of intermediate cells (E(m)) to the EP, a comparison was made between the effects of K(+) channel blockers on the E(m) and those on the EP. The E(m) of dissociated guinea pig intermediate cells was measured in the zero-current clamp mode of the whole-cell patch clamp configuration. The E(m) changed by 55.1 mV per 10-fold changes in extracellular K(+) concentration. Ba(2+), Cs(+), and quinine depressed the E(m) in a dose-dependent manner, whereas tetraethylammonium at 30 mM and 4-aminopyridine at 10 mM had no effect. The reduction of the E(m) by Ba(2+) and Cs(+) was enhanced by lowering the extracellular K(+) concentration from 3.6 mM to 1.2 mM. To examine the effect of the K(+) channel blockers on the EP, the EP of guinea pigs was maintained by vascular perfusion, and K(+) channel blockers were administered to the artificial blood. Ba(2+), Cs(+) and quinine depressed the EP in a dose-dependent manner, whereas tetraethylammonium at 30 mM and 4-aminopyridine at 10 mM did not change the EP. A 10-fold increase in the K(+) concentration in the artificial blood caused a minor decrease in the EP of only 10.6 mV. The changes in the EP were similar to those seen in the E(m) obtained at the lower extracellular K(+) concentration of 1.2 mM. On the basis of these results, we propose that the EP is critically dependent on the voltage jump across the plasma membrane of intermediate cells, and that K(+) concentration in the intercellular space in the stria vascularis may be actively controlled at a concentration lower than the plasma level. PMID:11053131

  17. Corticotropin-Releasing Factor Modulation of Forebrain GABAergic Transmission has a Pivotal Role in the Expression of Anabolic Steroid-Induced Anxiety in the Female Mouse

    PubMed Central

    Oberlander, Joseph G; Henderson, Leslie P

    2012-01-01

    Increased anxiety is commonly observed in individuals who illicitly administer anabolic androgenic steroids (AAS). Behavioral effects of steroid abuse have become an increasing concern in adults and adolescents of both sexes. The dorsolateral bed nucleus of the stria terminalis (dlBnST) has a critical role in the expression of diffuse anxiety and is a key site of action for the anxiogenic neuromodulator, corticotropin releasing factor (CRF). Here we demonstrate that chronic, but not acute, exposure of female mice during adolescence to AAS augments anxiety-like behaviors; effects that were blocked by central infusion of the CRF receptor type 1 antagonist, antalarmin. AAS treatment selectively increased action potential (AP) firing in neurons of the central amygdala (CeA) that project to the dlBnST, increased the frequency of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in dlBnST target neurons, and decreased both c-FOS immunoreactivity (IR) and AP frequency in these postsynaptic cells. Acute application of antalarmin abrogated the enhancement of GABAergic inhibition induced by chronic AAS exposure whereas application of CRF to brain slices of naïve mice mimicked the actions of this treatment. These results, in concert with previous data demonstrating that chronic AAS treatment results in enhanced levels of CRF mRNA in the CeA and increased CRF-IR in the dlBnST neuropil, are consistent with a mechanism in which the enhanced anxiety elicited by chronic AAS exposure involves augmented inhibitory activity of CeA afferents to the dlBnST and CRF-dependent enhancement of GABAergic inhibition in this brain region. PMID:22298120

  18. Increased dietary sodium alters Fos expression in the lamina terminalis during intravenous angiotensin II infusion.

    PubMed

    Bealer, Steven L; Metcalf, Cameron S; Heyborne, Ryan

    2007-03-01

    These studies examined the effects of increased dietary sodium on expression of Fos, the protein product of c-fos, in forebrain structures in the rat following intravenous infusion with angiotensin II (AngII). Animals were provided with either tap water (Tap) or isotonic saline solution (Iso) as their sole drinking fluid for 3-5 weeks prior to testing. Rats were then implanted with catheters in a femoral artery and vein. The following day, the conscious, unrestrained animals received iv infusion of either isotonic saline (Veh), AngII, or phenylephrine (Phen) for 2 h. Blood pressure and heart rate were monitored continuously throughout the procedure. Brains were subsequently processed for evaluation of Fos-like immunoreactivity (Fos-Li IR) in the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO), and the median preoptic nucleus (MnPO). Fos-Li IR was significantly increased in the SFO and OVLT of animals consuming both Tap and Iso following AngII, but not Phen, compared to Veh infusions. Furthermore, Fos-Li IR in the MnPO was increased following AngII infusion in rats consuming a high sodium diet, but not in animals drinking Tap. These data suggest that increased dietary sodium sensitizes the MnPO neurons to excitatory input from brain areas responding to circulating AngII.

  19. A case of transient hypothermia after trans-lamina terminalis and third ventricle clipping of an extremely high-position basilar tip aneurysm

    PubMed Central

    Ikawa, Fusao; Hamasaki, Osamu; Kurokawa, Yasuharu; Yonezawa, Ushio; Kurisu, Kaoru

    2015-01-01

    Reports on the trans-lamina terminalis and trans-third ventricular approach are rare. The risk associated with this approach is unknown. After an unsuccessful endovascular surgery, we performed direct surgical clipping via the third ventricle on a 78-year-old woman presenting with an extremely high-positioned, ruptured basilar tip aneurysm. She experienced transient hypothermia for 5 days, and it was considered that this was due to hypothalamic dysfunction. It is necessary to recognize that there is the potential for hypothermia after surgery via the lamina terminalis and third ventricle, even though the mechanisms of hypothalamic thermoregulation are still unclear. PMID:27489684

  20. FMRFamide-like immunoreactive nervus terminalis innervation to the pituitary in the catfish, Clarias batrachus (Linn.): demonstration by lesion and immunocytochemical techniques

    NASA Technical Reports Server (NTRS)

    Krishna, N. S.; Subhedar, N.; Schreibman, M. P.

    1992-01-01

    Certain thick FMRFamide-like immunoreactive fibers arising from the ganglion cells of nervus terminalis in the olfactory bulb of Clarias batrachus can be traced centripetally through the medial olfactory tract, telencephalon, lateral preoptic area, tuberal area, and hypothalamohypophysial tract to the pituitary. Following 6 days of bilateral olfactory tract transection, the immunoreactivity in the thick fibers, caudal to the lesion site, was partially eliminated, whereas after 10 and 14 days, it was totally abolished in the processes en route to the pituitary. The results indicate a direct innervation of the pituitary gland by the FMRFamide-like peptide containing fibers of the nervus terminalis.

  1. Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

    PubMed Central

    de Groot, John C.M.J.; van Iperen, Liesbeth; Huisman, Margriet A.; Frijns, Johan H.M.

    2015-01-01

    ABSTRACT Sensorineural hearing loss (SNHL) is one of the most common congenital disorders in humans, afflicting one in every thousand newborns. The majority is of heritable origin and can be divided in syndromic and nonsyndromic forms. Knowledge of the expression profile of affected genes in the human fetal cochlea is limited, and as many of the gene mutations causing SNHL likely affect the stria vascularis or cochlear potassium homeostasis (both essential to hearing), a better insight into the embryological development of this organ is needed to understand SNHL etiologies. We present an investigation on the development of the stria vascularis in the human fetal cochlea between 9 and 18 weeks of gestation (W9–W18) and show the cochlear expression dynamics of key potassium‐regulating proteins. At W12, MITF+/SOX10+/KIT+ neural‐crest‐derived melanocytes migrated into the cochlea and penetrated the basement membrane of the lateral wall epithelium, developing into the intermediate cells of the stria vascularis. These melanocytes tightly integrated with Na+/K+‐ATPase‐positive marginal cells, which started to express KCNQ1 in their apical membrane at W16. At W18, KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30 were expressed in the cells in the outer sulcus, but not in the spiral ligament. Finally, we investigated GJA1/CX43 and GJE1/CX23 expression, and suggest that GJE1 presents a potential new SNHL associated locus. Our study helps to better understand human cochlear development, provides more insight into multiple forms of hereditary SNHL, and suggests that human hearing does not commence before the third trimester of pregnancy. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1219–1240, 2015 PMID:25663387

  2. A Switch in Keystone Seed-Dispersing Ant Genera between Two Elevations for a Myrmecochorous Plant, Acacia terminalis.

    PubMed

    Thomson, Fiona J; Auld, Tony D; Ramp, Daniel; Kingsford, Richard T

    2016-01-01

    The dispersal capacity of plant species that rely on animals to disperse their seeds (biotic dispersal) can alter with changes to the populations of their keystone dispersal vectors. Knowledge on how biotic dispersal systems vary across landscapes allows better understanding of factors driving plant persistence. Myrmecochory, seed dispersal by ants, is a common method of biotic dispersal for many plant species throughout the world. We tested if the seed dispersal system of Acacia terminalis (Fabaceae), a known myrmecochore, differed between two elevations in the Greater Blue Mountains World Heritage Area, in southeastern Australia. We compared ant assemblages, seed removal rates of ants and other vertebrates (bird and mammal) and the dominant seed-dispersing ant genera. At low elevations (c. 200 m a.s.l) seed removal was predominantly by ants, however, at high elevation sites (c. 700 m a.s.l) vertebrate seed dispersers or seed predators were present, removing over 60% of seeds from experimental depots when ants were excluded. We found a switch in the keystone seed-dispersing ant genera from Rhytidoponera at low elevations sites to Aphaenogaster at high elevation sites. This resulted in more seeds being removed faster at low elevation sites compared to high elevation sites, however long-term seed removal rates were equal between elevations. Differences in the keystone seed removalist, and the addition of an alternate dispersal vector or seed predator at high elevations, will result in different dispersal and establishment patterns for A. terminalis at different elevations. These differences in dispersal concur with other global studies that report myrmecochorous dispersal systems alter with elevation.

  3. A Switch in Keystone Seed-Dispersing Ant Genera between Two Elevations for a Myrmecochorous Plant, Acacia terminalis

    PubMed Central

    Thomson, Fiona J.; Auld, Tony D.; Ramp, Daniel; Kingsford, Richard T.

    2016-01-01

    The dispersal capacity of plant species that rely on animals to disperse their seeds (biotic dispersal) can alter with changes to the populations of their keystone dispersal vectors. Knowledge on how biotic dispersal systems vary across landscapes allows better understanding of factors driving plant persistence. Myrmecochory, seed dispersal by ants, is a common method of biotic dispersal for many plant species throughout the world. We tested if the seed dispersal system of Acacia terminalis (Fabaceae), a known myrmecochore, differed between two elevations in the Greater Blue Mountains World Heritage Area, in southeastern Australia. We compared ant assemblages, seed removal rates of ants and other vertebrates (bird and mammal) and the dominant seed-dispersing ant genera. At low elevations (c. 200 m a.s.l) seed removal was predominantly by ants, however, at high elevation sites (c. 700 m a.s.l) vertebrate seed dispersers or seed predators were present, removing over 60% of seeds from experimental depots when ants were excluded. We found a switch in the keystone seed-dispersing ant genera from Rhytidoponera at low elevations sites to Aphaenogaster at high elevation sites. This resulted in more seeds being removed faster at low elevation sites compared to high elevation sites, however long-term seed removal rates were equal between elevations. Differences in the keystone seed removalist, and the addition of an alternate dispersal vector or seed predator at high elevations, will result in different dispersal and establishment patterns for A. terminalis at different elevations. These differences in dispersal concur with other global studies that report myrmecochorous dispersal systems alter with elevation. PMID:27310262

  4. Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain.

    PubMed

    Van Bockstaele, Elisabeth J; Qian, Yaping; Sterling, Robert C; Page, Michelle E

    2008-05-15

    The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone-precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pre-treatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional 4 h. At the end of the experiment

  5. Androgen receptors and estrogen receptors are colocalized in male rat hypothalamic and limbic neurons that express Fos immunoreactivity induced by mating.

    PubMed

    Gréco, B; Edwards, D A; Michael, R P; Clancy, A N

    1998-01-01

    Conversion of testosterone into estradiol is important for male rat sexual behavior, and both steroids probably contribute to mating. The distributions of neurons containing androgen receptors (AR) and estrogen receptors (ER) overlap, and many AR-immunoreactive (AR-ir) neurons express Fos immunoreactivity (Fos-ir) induced by mating. Because mating-induced Fos-ir in the male rat occurs mainly in AR-ir neurons, and because both steroids are important for mating, we hypothesized that (i) AR-ir and ER-ir are colocalized and that (ii) some of these neurons are activated during mating. We examined, in adjacent sections from the medial preoptic area (MPN) through the central tegmental field (CTF), the expression of ER-ir in: (i) AR-ir-containing neurons, and (ii) Fos-ir-expressive neurons. PG21 anti-AR, OA-11-824 anti-c-fos, H222 or 1D5 anti-ER primary antibodies were visualized, respectively, with cyanine-conjugated, fluorescein- or cyanine-conjugated, and fluorescein-conjugated secondary antibodies in male rats which were killed 1 h after ejaculating with a receptive female. In MPN, bed nucleus of the stria terminalis (BNST), and medial amygdala (MEA), 80-90% of ER-ir labeling occurred in AR-ir-positive neurons but only about 30% of AR-ir neurons were ER-ir-positive. No ER-ir was found in the CTF. This suggests the presence of three types of brain neurons sensitive to gonadal steroid hormones: neurons sensitive to androgens only, neurons sensitive to both androgens and estrogens, and neurons sensitive to estrogens only. About 50% of ER-ir labeling occurred in cells expressing mating-induced Fos-ir but only about 30% of Fos-ir neurons were ER-ir-positive. These findings suggest that, in the MPN, at least two different neuronal populations are activated during mating: the first contains AR-ir only and the second contains AR-ir and ER-ir. In the BNST and MEA, at least three hormonally sensitive populations are activated during mating: the two described above plus a third

  6. Regional Fos-expression induced by γ-hydroxybutyrate (GHB): comparison with γ-butyrolactone (GBL) and effects of co-administration of the GABAB antagonist SCH 50911 and putative GHB antagonist NCS-382.

    PubMed

    van Nieuwenhuijzen, P S; McGregor, I S; Chebib, M; Hunt, G E

    2014-09-26

    γ-Hydroxybutyrate (GHB) has a complex array of neural actions that include effects on its own high-affinity GHB receptor, the release of neuroactive steroids, and agonist actions at GABAA and GABAB receptors. We previously reported partial overlap in the c-Fos expression patterns produced by GHB and the GABAB agonist, baclofen in rats. The present study extends these earlier findings by examining the extent to which GHB Fos expression and behavioral sedation are prevented by (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), a GABAB antagonist, and NCS-382, a putative antagonist at the high-affinity GHB receptor. We also compare Fos expression caused by GHB and its precursor γ-butyrolactone (GBL), which is a pro-drug for GHB but lacks the high sodium content of the parent GHB molecule. Both GHB (1,000 mg/kg) and GBL (600 mg/kg) induced rapid sedation in rats that lasted over 90 min and caused similar Fos expression patterns, albeit with GBL causing greater activation of the nucleus accumbens (core and shell) and dentate gyrus (granular layer). Pretreatment with SCH 50911 (100mg/kg) partly reversed the sedative effects of GHB and significantly reduced GHB-induced Fos expression in only four regions: the tenia tecta, lateral habenula, dorsal raphe and laterodorsal tegmental nucleus. NCS-382 (50mg/kg) had no effect on GHB-induced sedation or Fos expression. When given alone, both NCS-382 and SCH 50911 increased Fos expression in the bed nucleus of the stria terminalis, central amygdala, parasubthalamic nucleus and nucleus of the solitary tract. SCH 50911 alone affected the Islands of Calleja and the medial, central and paraventricular thalamic nuclei. Overall, this study shows a surprising lack of reversal of GHB-induced Fos expression by two relevant antagonists, both of which have marked intrinsic actions. This may reflect the limited doses tested but also suggests that GHB Fos expression reflects mechanisms independent of GHB and GABAB receptors.

  7. Congenital generalized hypertrichosis terminalis: a proposed classification and a plea to avoid the ambiguous term "Ambras syndrome".

    PubMed

    Chen, WenChieh; Ring, Johannes; Happle, Rudolf

    2015-01-01

    Congenital generalized hypertrichosis terminalis (CGHT) is a heterogenous group of diseases with continuing excessive growth of terminal hair. "Ambras syndrome" was first coined by Baumeister in 1993 to describe a case of nonsyndromic CGHT which was erroneously analogized to the portrait paintings of Petrus Gonzales and his children, exhibited in Ambras Castle near Innsbruck, Austria. This family probably, a syndromic type with abnormal dentition, inherited as an autosomal dominant trait. CGHT associated with gingival hyperplasia is probably a particular entity typified by the historical cases of Julia Pastrana and her son. An X-linked type of CGHT has likewise been categorized as "Ambras syndrome". Moreover, some reports have mistakenly classified "Ambras syndrome" as an example of hypertrichosis lanuginosa. Potential gene loci identified so far may include 8q22, 17q24.2-q24.3 and Xq24-q27.1. The designation "Ambras syndrome" has thus been applied to various types of congenital hypertrichosis that differ to such degree that the name "Ambras" has no specific meaning, neither in the past nor in the future. Hence, this misleading term should now be jettisoned.

  8. Deafness in LIMP2-deficient mice due to early loss of the potassium channel KCNQ1/KCNE1 in marginal cells of the stria vascularis.

    PubMed

    Knipper, Marlies; Claussen, Cathrin; Rüttiger, Lukas; Zimmermann, Ulrike; Lüllmann-Rauch, Renate; Eskelinen, Eeva-Liisa; Schröder, Jenny; Schwake, Michael; Saftig, Paul

    2006-10-01

    Our previous studies revealed a critical role of the lysosomal membrane protein LIMP2 in the regulation of membrane transport processes in the endocytic pathway. Here we show that LIMP2-deficient mice display a progressive high-frequency hearing loss and decreased otoacoustic emissions as early as 4 weeks of age. In temporal overlap to hearing impairment, fluorescence immunohistochemical studies revealed that the potassium channel KCNQ1 and its beta-subunit KCNE1 were almost completely lost in the luminal part of marginal cells in the stria vascularis, affecting first higher and later also lower frequency processing cochlear turns. Concomitant with this, the expression of megalin, a multiligand endocytic receptor, was reduced in luminal surfaces of marginal cells within the stria vascularis. KCNQ1/KCNE1 and megalin were also lost in the dark cells of the vestibular system. Although LIMP2 is normally expressed in all cells of the stria vascularis, in the organ of Corti and cochlear neurons, the lack of LIMP2 preferentially caused a loss of KCNQ1/KCNE1 and megalin, and structural changes were only seen months later, indicating that these proteins are highly sensitive to disturbances in the lysosomal pathway. The spatio-temporal correlation of the loss of KCNQ1/KCNE1 surface expression and loss of hearing thresholds supports the notion that the decline of functional KCNQ1/KCNE1 is likely to be the primary cause of the hearing loss. Our findings suggest an important role for LIMP2 in the control of the localization and the level of apically expressed membrane proteins such as KCNQ1, KCNE1 and megalin in the stria vascularis.

  9. Ion transport mechanisms responsible for K+ secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro.

    PubMed

    Wangemann, P; Liu, J; Marcus, D C

    1995-04-01

    It has long been accepted that marginal cells of stria vascularis are involved in the generation of the endocochlear potential and the secretion of K+. The present study was designed to provide evidence for this hypothesis and for a cell model proposed to explain K+ secretion and the generation of the endocochlear potential. Stria vascularis from the cochlea of the gerbil was isolated and mounted into a micro-Ussing chamber such that the apical and basolateral membrane of marginal cells could be perfused independently. In this preparation, the transepithelial voltage (Vt) and resistance (Rt) were measured across marginal cells and the resulting equivalent short circuit current (Isc) was calculated (Isc = Vt/Rt). Further, K+ secretion (JK+,probe) was measured with a K(+)-selective vibrating probe in the vicinity of the apical membrane. In the absence of extrinsic chemical driving forces, when both sides of the marginal cell epithelium were bathed with a perilymph-like solution, Vt was 8 mV (apical side positive), Rt was 10 ohm-cm2 and Isc was 850 microA/cm2 (N = 27). JK+,probe was outwardly directed from the apical membrane and reversibly inhibited by basolateral bumetanide, a blocker of the Na+/Cl-/K+ cotransporter. On the basolateral but not apical side, oubain and bumetanide each caused a decline of Vt and an increase of Rt suggesting the presence of the Na,K-ATPase and the Na+/Cl-/K+ cotransporter in the basolateral membrane. The responses to [Cl-] steps demonstrated a significant Cl- conductance in the basolateral membrane and a small Cl- conductance in the paracellular pathway or the apical membrane. The responses to [Na+] steps demonstrated no significant Na+ conductance in the basolateral membrane and a small Na+ or nonselective cation conductance in the apical membrane or paracellular pathway. The responses to [K+] steps demonstrated a large K+ conductance in the apical membrane. Apical application of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS

  10. Effective G-protein coupling of Y2 receptors along axonal fiber tracts and its relevance for epilepsy.

    PubMed

    Dum, Elisabeth; Fürtinger, Sabine; Gasser, Elisabeth; Bukovac, Anneliese; Drexel, Meinrad; Tasan, Ramon; Sperk, Günther

    2017-02-01

    Neuropeptide Y (NPY)-Y2 receptors are G-protein coupled receptors and, upon activation, induce opening of potassium channels or closing of calcium channels. They are generally presynaptically located. Depending on the neuron in which they are expressed they mediate inhibition of release of NPY and of the neuron's classical transmitter GABA, glutamate or noradrenaline, respectively. Here we provide evidence that Y2 receptor binding is inhibited dose-dependently by GTPγS along Schaffer collaterals, the stria terminalis and the fimbria indicating that Y2 receptors are functionally coupled to G-proteins along these fiber tracts. Double immune fluorescence revealed coexistence of Y2-immunoreactivity with β-tubulin, a marker for axons in the stria terminalis, but not with synaptophysin labeling presynaptic terminals, supporting the localization of Y2 receptors along axonal tracts. After kainic acid-induced seizures in rats, GTPγS-induced inhibition of Y2 receptor binding is facilitated in the Schaffer collaterals but not in the stria terminalis. Our data indicate that Y2 receptors are not only located at nerve terminals but also along fiber tracts and are there functionally coupled to G-proteins.

  11. The Effect of Fenestration of Lamina Terminalis on the Vasospasm and Shunt-Dependent Hydrocephalus in Patients Following Subarachnoid Haemorrhage

    PubMed Central

    Hatefi, Masoud; Azhary, Shirzad; Naebaghaee, Hussein; Mohamadi, Hasan Reza

    2015-01-01

    Background and Aims: SAH (Sub Arachnoid Haemorrhage) is a life threatening that is associated with complications such as vasospasm and shunt-dependent hydrocephalus. The purpose of this study was to assess the effect of FLT (Fenestration of Lamina Terminalis) on the incidence of vasospasm and shunt-dependent hydrocephalus in ACoA (Anterior Communicating Artery) aneurismal in SAH. Materials and Methods: The data of 50 ruptured ACoA aneurism patients were selected during the year 2001-2009 admitted to Imam Hussein hospital, Tehran, IR. In a randomized double-blind trial patients assigned in two group {with fenestration (FLT, n=25), without fenestration (No FLT, n=25)}. All patients underwent craniotomy by a single neurosurgeon. Patient’s age, sex, Hunt-Hess grade, Fisher grade, vasospasm, presence of hydrocephalus and incidences of shunt-dependent hydrocephalus were compared between groups. Results: There were no significant differences among groups in relation to demographic characteristics, neurological scale scores (Hunt-Hess grade) and the severity of the SAH (Fisher grade) (p>0.05). The rate of hydrocephalus on admission, were 24% and 16% in FLT and no FLT group respectively (p>0.05). The shunt placement postoperatively in FLT and no FLT group were 16% and 12% respectively (p>0.05). The clinical vasospasm was 20% and 24% in FLT and no FLT group respectively (p>0.05). Conclusion: Despite FLT can be a safe method there were not significant differences of FLT on the incidence of vasospasm and shunt-dependent hydrocephalus. A systematic evaluation with multisurgeon, multicentre and with greater sample size to disclose reality is suggested. PMID:26393164

  12. Expression and Vesicular Localization of Mouse Trpml3 in Stria Vascularis, Hair Cells, and Vomeronasal and Olfactory Receptor Neurons

    PubMed Central

    Flores, Emma N.; García-Añoveros, Jaime

    2013-01-01

    TRPML3 is a member of the mucolipin branch of the transient receptor potential cation channel family. A dominant missense mutation in Trpml3 (also known as Mcoln3) causes deafness and vestibular impairment characterized by stereocilia disorganization, hair cell loss, and endocochlear potential reduction. Both marginal cells of the stria vascularis and hair cells express Trpml3 mRNA. Here we used in situ hybridization, quantitative RT-qPCR, and immunohistochemistry with several antisera raised against TRPML3 to determine the expression and subcellular distribution of TRPML3 in the inner ear as well as in other sensory organs. We also use Trpml3 knockout tissues to distinguish TRPML3-specific from nonspecific immunoreactivities. We find that TRPML3 localizes to vesicles of hair cells and strial marginal cells but not to stereociliary ankle links or pillar cells, which nonspecifically react with two antisera raised against TRPML3. Upon cochlear maturation, TRPML3 protein is redistributed to perinuclear vesicles of strial marginal cells and is augmented in inner hair cells vs. outer hair cells. Mouse somato-sensory neurons, retinal neurons, and taste receptor cells do not appear to express physiologically relevant levels of TRPML3. Finally, we found that vomeronasal and olfactory sensory receptor cells do express TRPML3 mRNA and protein, which localizes to vesicles in their somas and dendrites as well as at apical den dritic knobs. PMID:21344404

  13. The effect of fenestration of the lamina terminalis on the incidence of shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage (FISH)

    PubMed Central

    Tao, Chuanyuan; Fan, Chaofeng; Hu, Xin; Ma, Junpeng; Ma, Lu; Li, Hao; Liu, Yi; Sun, Hong; He, Min; You, Chao

    2016-01-01

    Abstract Background: Shunt-dependent hydrocephalus (SDH) is a well-known sequela following aneurysmal hemorrhage, adversely affecting the outcome after securing ruptured aneurysm. Fenestration of lamina terminalis (FLT) creates an anterior ventriculostomy, facilitates cerebrospinal fluid circulation and clot clearance in the basal cistern. However, controversy exists over whether microsurgical FLT during aneurysm repair can decrease the incidence of SDH. Aims: The study is designed to determine the efficacy of lamina terminalis fenestration on the reduction of SDH after aneurysm clipping. Methods/Design: A total of 288 patients who meet the inclusion criteria will be randomized into single aneurysm clipping or aneurysm clipping plus FLT in the Department of Neurosurgery, West China Hospital. Follow-up was performed 1, 3, 6, and 12 months after aneurysm clipping. The primary outcome is the incidence of SDH and the secondary outcomes include cerebral vasospasm, functional outcome evaluated by the modified Rankin Scale and Extended Glasgow Outcome Scale, and mortality. Discussion: The FISH trial is a large randomized, parallel controlled clinical trial to define the therapeutic value of FLT, the results of which will help to guide the surgical procedure and resolve the long-puzzled debate in the neurosurgical community. Conclusions: This protocol will determine the efficacy of FLT in the setting of aneurysmal subarachnoid hemorrhage. Trial registration identifier: http://www.chictr.org.cn/edit.aspx?pid=15691&htm=4 Chinese Clinical Trial Registry: ChiCTR-INR-16009249. PMID:28033279

  14. Studies on South-east Asian fireflies: Abscondita, a new genus with details of life history, flashing patterns and behaviour of Abs. chinensis (L.) and Abs. terminalis (Olivier) (Coleoptera: Lampyridae: Luciolinae).

    PubMed

    Ballantyne, Lesley; Fu, Xinhua; Lambkin, Christine; Jeng, Ming-Luen; Faust, Lynn; Wijekoon, M C D; Li, Daiqin; Zhu, Tengfui

    2013-01-01

    Abscondita, a new genus of fireflies from South-east Asia, is described from males and females of Abs. anceyi (Olivier 1883), Abs. cerata (Olivier 1911), Abs. chinensis (L. 1767), Abs. perplexa (Walker 1858), Abs. promelaena (Walker 1858) and Abs. terminalis (Olivier 1883), all transferred from Luciola Laporte. Both L. dubia Olivier 1903 and L. dejeani Gemminger 1870 are synonymised with Luciola perplexa (Walker), and L. aegrota Olivier 1891 and L. melaspis Bourgeois 1909 with L. promelaena Walker. Females are characterised by their bursa plates. Larvae are associated and described for Abs. anceyi (Olivier), Abs. chinensis (L.) and Abs. terminalis (Olivier). Taxonomic issues regarding the identification of species with very similar colouration of pale dorsum and black tipped elytra are addressed and in some cases resolved. A neotype for Luciola chinensis (L.) is erected and Luciola praeusta (Kiesenwetter 1874) is synonymised with L. chinensis (L.). Descriptions of life histories, biology and flashing patterns of populations of Abs. chinensis and Abs. terminalis from central China are included. A bs. terminalis is the first Asian firefly known to possess multiple flash trains where males are documented to display with repeating flash trains.

  15. De Novo 17q24.2-q24.3 microdeletion presenting with generalized hypertrichosis terminalis, gingival fibromatous hyperplasia, and distinctive facial features.

    PubMed

    Afifi, Hanan H; Fukai, Ryoko; Miyake, Noriko; Gamal El Din, Amina A; Eid, Maha M; Eid, Ola M; Thomas, Manal M; El-Badry, Tarek H; Tosson, Angie M S; Abdel-Salam, Ghada M H; Matsumoto, Naomichi

    2015-10-01

    Generalized hypertrichosis is a feature of several genetic disorders, and the nosology of these entities is still provisional. Recent studies have implicated chromosome 17q24.2-q24.3 microdeletion and the reciprocal microduplication in a very rare form of congenital generalized hypertrichosis terminalis (CGHT) with or without gingival hyperplasia. Here, we report on a 5-year-old Egyptian girl born to consanguineous parents. The girl presented with CGHT and gingival hyperplasia for whom we performed detailed clinical, pathological, and molecular studies. The girl had coarse facies characterized by bilateral epicanthic folds, thick and abundant eyelashes, a broad nose, full cheeks, and lips that constituted the distinctive facial features for this syndrome. Biopsy of the gingiva showed epithelial marked acanthosis and hyperkeratosis with hyperplastic thick collagen bundles and dense fibrosis in the underlying tissues. Array analysis indicated a 17q24.2-q24.3 chromosomal microdeletion. We validated this microdeletion by real-time quantitative PCR and confirmed a perfect co-segregation of the disease phenotype within the family. In summary, this study indicates that 17q24.2-q24.3 microdeletion caused CGHT with gingival hyperplasia and distinctive facies, which should be differentiated from the autosomal recessive type that lacks the distinctive facies.

  16. Differential effects of unilateral lesions in the medial amygdala on spontaneous and induced ovulation.

    PubMed

    Sanchez, M A; Dominguez, R

    1995-01-01

    The possible existence of asymmetry in the control of ovulation by the medial amygdala was explored. Unilateral lesions of the medial amygdala were performed on each day of the estrous cycle. The estral index diminished in almost all animals with a lesion in the right side of medial amygdala. Lesions of the right medial amygdala, when performed on diestrus-1, resulted in a significant decrease in the number of rats ovulating compared to controls (4/8 vs. 8/8, p < 0.05). In ovulating animals a significant reduction in the number of ova shed by the left ovary was found (2.2 +/- 0.8 vs. 6.3 +/- 0.8, p < 0.05). Lesions of the stria terminalis performed on diestrus-1 did not affect ovulation. In a second experiment, administration of GnRH did not restore ovulation in rats with lesions of the right medial amygdala. However, sequential injections of PMSG-hCG did result in ovulation by all members of a group of lesioned animals. In this last condition a significant decrease in the number of ova shed by the right ovary was found compared to animals in the lesion-only condition (1.5 +/- 0.5 vs. 6.0 +/- 1.5, p < 0.05). These data suggest that control of ovulation by the medial amygdala is asymmetric and varies during the estrous cycle.

  17. [Deafness, induced by sodium ethacrynate in guinea pigs, alleviated by microwave treatment].

    PubMed

    Chen, X M; Din, D L; Luo, D F; Huangfu, M S; Jin, X M

    1992-01-01

    Microwave is used to treat temporal hearing loss caused by intravenous injection of the ethacrynic acid in guinea pigs. The recovery of hearing is much faster in the treated groups than in the control group. The article proposes possible mechanism of the effects against the ethacrynic acid induced deafness and assume that the result of this research can provide an experimental basis for treatment of some perceptive deafness due to ischemia of stria vascularis of the cochlea.

  18. Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo)

    PubMed Central

    Moeller, John F.; Meredith, Michael

    2010-01-01

    The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RFamide-like peptides. To define further the cell populations and connectivity, we used double-label immuno-cytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH immunoreactive (ir) cell-profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies, and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT) negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. PMID:20950589

  19. Copy-number mutations on chromosome 17q24.2-q24.3 in congenital generalized hypertrichosis terminalis with or without gingival hyperplasia.

    PubMed

    Sun, Miao; Li, Ning; Dong, Wu; Chen, Zugen; Liu, Qing; Xu, Yiming; He, Guang; Shi, Yongyong; Li, Xin; Hao, Jiajie; Luo, Yang; Shang, Dandan; Lv, Dan; Ma, Fen; Zhang, Dai; Hua, Rui; Lu, Chaoxia; Wen, Yaran; Cao, Lihua; Irvine, Alan D; McLean, W H Irwin; Dong, Qi; Wang, Ming-Rong; Yu, Jun; He, Lin; Lo, Wilson H Y; Zhang, Xue

    2009-06-01

    Congenital generalized hypertrichosis terminalis (CGHT) is a rare condition characterized by universal excessive growth of pigmented terminal hairs and often accompanied with gingival hyperplasia. In the present study, we describe three Han Chinese families with autosomal-dominant CGHT and a sporadic case with extreme CGHT and gingival hyperplasia. We first did a genome-wide linkage scan in a large four-generation family. Our parametric multipoint linkage analysis revealed a genetic locus for CGHT on chromosome 17q24.2-q24.3. Further two-point linkage and haplotyping with microsatellite markers from the same chromosome region confirmed the genetic mapping and showed in all the families a microdeletion within the critical region that was present in all affected individuals but not in unaffected family members. We then carried out copy-number analysis with the Affymetrix Genome-Wide Human SNP Array 6.0 and detected genomic microdeletions of different sizes and with different breakpoints in the three families. We validated these microdeletions by real-time quantitative PCR and confirmed their perfect cosegregation with the disease phenotype in the three families. In the sporadic case, however, we found a de novo microduplication. Two-color interphase FISH analysis demonstrated that the duplication was inverted. These copy-number variations (CNVs) shared a common genomic region in which CNV is not reported in the public database and was not detected in our 434 unrelated Han Chinese normal controls. Thus, pathogenic copy-number mutations on 17q24.2-q24.3 are responsible for CGHT with or without gingival hyperplasia. Our work identifies CGHT as a genomic disorder.

  20. Combined effects of dietary fructooligosaccharide and Bacillus licheniformis on innate immunity, antioxidant capability and disease resistance of triangular bream (Megalobrama terminalis).

    PubMed

    Zhang, Chun-Nuan; Li, Xiang-Fei; Xu, Wei-Na; Jiang, Guang-Zhen; Lu, Kang-Le; Wang, Li-Na; Liu, Wen-Bin

    2013-11-01

    This study was conducted to investigate the effects of fructooligosaccharide (FOS) and Bacillus licheniformis (B. licheniformis) and their interaction on innate immunity, antioxidant capability and disease resistance of triangular bream Megalobrama terminalis (average initial weight 30.5 ± 0.5 g). Nine experimental diets were formulated to contain three FOS levels (0, 0.3% and 0.6%) and three B. licheniformis levels (0, 1 × 10(7), 5 × 10(7) CFU g(-1)) according to a 3 × 3 factorial design. At the end of the 8-week feeding trial, fish were challenged by Aeromonas hydrophila (A. hydrophila) and survival rate was recorded for the next 7 days. The results showed that leucocyte counts, alternative complement activity as well as total serum protein and globulin contents all increased significantly (P < 0.05) as dietary B. licheniformis levels increased from 0 to 1 × 10(7) CFU g(-1), while little difference (P > 0.05) was observed in these parameters in terms of dietary FOS levels. Both plasma alkaline phosphatase and phenoloxidase activities were significantly (P < 0.05) affected only by dietary FOS levels with the highest values observed in fish fed 0.6 and 0.3% FOS, respectively. Both immunoglobulin M content and liver superoxide dismutase (SOD) activity were significantly affected (P > 0.05) by both FOS and B. licheniformis. Liver catalase, glutathione peroxidase as well as plasma SOD activities of fish fed 1 × 10(7) CFU g(-1)B. licheniformis were all significantly (P < 0.05) higher than that of the other groups, whereas the opposite was true for malondialdehyde content. After A. hydrophila challenge, survival rate was not affected (P > 0.05) by either FOS levels or B. licheniformis contents, whereas a significant (P < 0.05) interaction between these two substances was observed with the highest value observed in fish fed 0.3% FOS and 1 × 10(7) CFU g(-1)B. licheniformis. The results of this study indicated that dietary FOS and B. licheniformis could

  1. Brief pup exposure induces Fos expression in the lateral habenula and serotonergic caudal dorsal raphe nucleus of paternally experienced male California mice (Peromyscus californicus).

    PubMed

    de Jong, T R; Measor, K R; Chauke, M; Harris, B N; Saltzman, W

    2010-09-01

    Fathers play a substantial role in infant care in a small but significant number of mammalian species, including humans. However, the neural circuitry controlling paternal behavior is much less understood than its female counterpart. In order to characterize brain areas activated by paternal care, male California mice were separated from their female mate and litter for 3 h and then exposed to a pup or a control object (a glass pebble with the approximate size and oblong shape of a newborn pup) for 10 min. All males receiving a pup showed a strong paternal response towards it, whereas males receiving a pebble interacted with it only occasionally. Despite the clear behavioral differences, exposure to a pup did not increase Fos-like immunoreactivity (Fos-LIR) compared to a pebble in brain areas previously found to be associated with parental care, including the medial preoptic nucleus and medial bed nucleus of the stria terminalis. Pup exposure did, however, significantly increase Fos-LIR in the lateral habenula (LHb) and in predominantly serotonergic neurons in the caudal dorsal raphe nucleus (DRC), as compared to pebble exposure. Both the LHb and DRC are known to be involved in the behavioral responses to strong emotional stimuli; therefore, these areas might play a role in controlling parental behavior in male California mice.

  2. Unexpected Presence of Graminan- and Levan-Type Fructans in the Evergreen Frost-Hardy Eudicot Pachysandra terminalis (Buxaceae): Purification, Cloning, and Functional Analysis of a 6-SST/6-SFT Enzyme1[W

    PubMed Central

    Van den Ende, Wim; Coopman, Marlies; Clerens, Stefan; Vergauwen, Rudy; Le Roy, Katrien; Lammens, Willem; Van Laere, André

    2011-01-01

    About 15% of flowering plants accumulate fructans. Inulin-type fructans with β(2,1) fructosyl linkages typically accumulate in the core eudicot families (e.g. Asteraceae), while levan-type fructans with β(2,6) linkages and branched, graminan-type fructans with mixed linkages predominate in monocot families. Here, we describe the unexpected finding that graminan- and levan-type fructans, as typically occurring in wheat (Triticum aestivum) and barley (Hordeum vulgare), also accumulate in Pachysandra terminalis, an evergreen, frost-hardy basal eudicot species. Part of the complex graminan- and levan-type fructans as accumulating in vivo can be produced in vitro by a sucrose:fructan 6-fructosyltransferase (6-SFT) enzyme with inherent sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan 6-exohydrolase side activities. This enzyme produces a series of cereal-like graminan- and levan-type fructans from sucrose as a single substrate. The 6-SST/6-SFT enzyme was fully purified by classic column chromatography. In-gel trypsin digestion led to reverse transcription-polymerase chain reaction-based cDNA cloning. The functionality of the 6-SST/6-SFT cDNA was demonstrated after heterologous expression in Pichia pastoris. Both the recombinant and native enzymes showed rather similar substrate specificity characteristics, including peculiar temperature-dependent inherent 1-SST and fructan 6-exohydrolase side activities. The finding that cereal-type fructans accumulate in a basal eudicot species further confirms the polyphyletic origin of fructan biosynthesis in nature. Our data suggest that the fructan syndrome in P. terminalis can be considered as a recent evolutionary event. Putative connections between abiotic stress and fructans are discussed. PMID:21037113

  3. Unexpected presence of graminan- and levan-type fructans in the evergreen frost-hardy eudicot Pachysandra terminalis (Buxaceae): purification, cloning, and functional analysis of a 6-SST/6-SFT enzyme.

    PubMed

    Van den Ende, Wim; Coopman, Marlies; Clerens, Stefan; Vergauwen, Rudy; Le Roy, Katrien; Lammens, Willem; Van Laere, André

    2011-01-01

    About 15% of flowering plants accumulate fructans. Inulin-type fructans with β(2,1) fructosyl linkages typically accumulate in the core eudicot families (e.g. Asteraceae), while levan-type fructans with β(2,6) linkages and branched, graminan-type fructans with mixed linkages predominate in monocot families. Here, we describe the unexpected finding that graminan- and levan-type fructans, as typically occurring in wheat (Triticum aestivum) and barley (Hordeum vulgare), also accumulate in Pachysandra terminalis, an evergreen, frost-hardy basal eudicot species. Part of the complex graminan- and levan-type fructans as accumulating in vivo can be produced in vitro by a sucrose:fructan 6-fructosyltransferase (6-SFT) enzyme with inherent sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan 6-exohydrolase side activities. This enzyme produces a series of cereal-like graminan- and levan-type fructans from sucrose as a single substrate. The 6-SST/6-SFT enzyme was fully purified by classic column chromatography. In-gel trypsin digestion led to reverse transcription-polymerase chain reaction-based cDNA cloning. The functionality of the 6-SST/6-SFT cDNA was demonstrated after heterologous expression in Pichia pastoris. Both the recombinant and native enzymes showed rather similar substrate specificity characteristics, including peculiar temperature-dependent inherent 1-SST and fructan 6-exohydrolase side activities. The finding that cereal-type fructans accumulate in a basal eudicot species further confirms the polyphyletic origin of fructan biosynthesis in nature. Our data suggest that the fructan syndrome in P. terminalis can be considered as a recent evolutionary event. Putative connections between abiotic stress and fructans are discussed.

  4. Amygdalar vocalization pathways in the squirrel monkey.

    PubMed

    Jürgens, U

    1982-06-10

    In 22 squirrel monkeys (Saimiri sciureus) vocalization-eliciting electrodes were implanted into the amygdala and along the trajectory of the stria terminalis. Then, lesions were placed in the stria terminalis, its bed nucleus, the ventral amygdalofugal pathway and several di- and mesencephalic structures in order to find out the pathways along which the amygdala exerts its vocalization-controlling influence. It was found that different call types are controlled by different pathways. Purring and chattering calls, which express a self-confident, challenging attitude and an attempt to recruit fellow-combatants in intra-specific mobbing, respectively, are controlled via the stria terminalis; alarm peep and groaning calls, in contrast, which indicate flight motivation and resentment, respectively, are triggered via the ventral amygdalofugal fibre bundle. Both pathways traverse the dorsolateral and dorsomedial hypothalamus, respectively, and unite in the periaqueductal grey of the midbrain.

  5. Effect of desipramine and citalopram treatment on forced swimming test-induced changes in cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in mice.

    PubMed

    Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Kim, Jin Wook; Kim, Jeong Min; Shin, Kyung Ho

    2014-05-01

    Recent study demonstrates antidepressant-like effect of cocaine- and amphetamine-regulated transcript (CART) in the forced swimming test (FST), but less is known about whether antidepressant treatments alter levels of CART immunoreactivity (CART-IR) in the FST. To explore this possibility, we assessed the treatment effects of desipramine and citalopram, which inhibit the reuptake of norepinephrine and serotonin into the presynaptic terminals, respectively, on changes in levels of CART-IR before and after the test swim in mouse brain. Levels of CART-IR in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), and hypothalamic paraventricular nucleus (PVN) were significantly increased before the test swim by desipramine and citalopram treatments. This increase in CART-IR in the AcbSh, dBNST, and PVN before the test swim remained elevated by desipramine treatment after the test swim, but this increase in these brain areas returned to near control levels after test swim by citalopram treatment. Citalopram, but not desipramine, treatment increased levels of CART-IR in the central nucleus of the amygdala (CeA) and the locus ceruleus (LC) before the test swim, and this increase was returned to control levels after the test swim in the CeA, but not in the LC. These results suggest common and distinct regulation of CART by desipramine and citalopram treatments in the FST and raise the possibility that CART in the AcbSh, dBNST, and CeA may be involved in antidepressant-like effect in the FST.

  6. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries.

    PubMed

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina

    2016-02-01

    Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption.

  7. Involvement of calpain-I and microRNA34 in kanamycin-induced apoptosis of inner ear cells.

    PubMed

    Yu, Li; Tang, Hao; Jiang, Xiao Hua; Tsang, Lai Ling; Chung, Yiu Wa; Chan, Hsiao Chang

    2010-12-01

    Inner ear cells, including hair cells, spiral ganglion cells, stria vascularis cells and supporting cells on the basilar membrane, play a major role in transducing hearing signals and regulating inner ear homoeostasis. However, their functions are often damaged by antibiotic-induced ototoxicity. Apoptosis is probably involved in inner ear cell injury following aminoglycoside treatment. Calpain, a calcium-dependent protease, is essential for mediating and promoting cell death. We have therefore investigated the involvement of calpain in the molecular mechanism underlying ototoxicity induced by the antibiotic kanamycin in mice. Kanamycin (750 mg/kg) mainly induced cell death of cochlear cells, including stria vascularis cells, supporting cells and spiral ganglion cells, but not hair cells within the organ of Corti. Cell death due to apoptosis occurred in a time-dependent manner with concomitant up-regulation of calpain expression. Furthermore, the expression levels of two microRNAs, mir34a and mir34c, were altered in a dose-dependent manner in cochlear cells. These novel findings demonstrated the involvement of both calpain and microRNAs in antibiotic-induced ototoxicity.

  8. An in vitro mouse model of congenital cytomegalovirus-induced pathogenesis of the inner ear cochlea.

    PubMed

    Melnick, Michael; Jaskoll, Tina

    2013-02-01

    Congenital human cytomegalovirus (CMV) infection is the leading nongenetic etiology of sensorineural hearing loss (SNHL) at birth and prelingual SNHL not expressed at birth. The paucity of temporal bone autopsy specimens from infants with congenital CMV infection has hindered the critical correlation of histopathology with pathogenesis. Here, we present an in vitro embryonic mouse model of CMV-infected cochleas that mimics the human sites of viral infection and associated pathology. There is a striking dysplasia/hyperplasia in mouse CMV-infected cochlear epithelium and mesenchyme, including organ of Corti hair and supporting cells and stria vascularis. This is concomitant with significant dysregulation of p19, p21, p27, and Pcna gene expression, as well as proliferating cell nuclear antigen (PCNA) protein expression. Other pathologies similar to those arising from known deafness gene mutations include downregulation of KCNQ1 protein expression in the stria vascularis, as well as hypoplastic and dysmorphic melanocytes. Thus, this model provides a relevant and reliable platform within which the detailed cell and molecular biology of CMV-induced deafness may be studied.

  9. Enduring attenuation of norepinephrine synaptic availability and augmentation of the pharmacological and behavioral effects of desipramine by repeated immobilization stress.

    PubMed

    Gonzáles, Marco A; Miranda, Ana Pamela; Orrego, Horacio; Silva, Rodolfo; Forray, María Inés

    2017-02-20

    Here we provide evidence that repeated immobilization stress (RIS) in rats induces a persistent increase in noradrenergic activity in the anterior aspects of the anterolateral bed nucleus of the stria terminalis (alBNST). This increase in noradrenergic activity results from both enhanced synthesis and reuptake of norepinephrine (NE). It leads to a decrease in the synaptic availability of NE, which elicits an augmented noradrenergic response to the inhibitors of NE reuptake (NRIs), such as desipramine (DMI), an antidepressant. The enduring depression-like behavior and the augmentation of the climbing behavior seen in repeatedly stressed rats following subchronic administration of DMI in the forced swimming test (FST) might be explained by a dysregulation of noradrenergic transmission observed in alBNST. Taken together, we propose that dysregulation of noradrenergic transmission such as the one described in the present work may represent a mechanism underlying major depressive disorders (MDD) with melancholic features in humans.

  10. A retracting wire knife for cutting fiber bundles and making sheet lesions of brain tissue.

    PubMed

    Shibata, M; Russell, I S

    1979-07-01

    A retracting knife which has two cutting wires for the transection of fiber bundles is described. The knife holds the fiber bundles of the stria terminalis between the two cutting wires and transects them by a shearing movement as the wires close. In addition, the feasability of such a knife producing a sheet lesion around the n. caudatus is also described.

  11. A Basal Forebrain Site Coordinates the Modulation of Endocrine and Behavioral Stress Responses via Divergent Neural Pathways

    PubMed Central

    Johnson, Shane B.; Emmons, Eric B.; Anderson, Rachel M.; Glanz, Ryan M.; Romig-Martin, Sara A.; Narayanan, Nandakumar S.; LaLumiere, Ryan T.

    2016-01-01

    The bed nuclei of the stria terminalis (BST) are critically important for integrating stress-related signals between the limbic forebrain and hypothalamo-pituitary-adrenal (HPA) effector neurons in the paraventricular hypothalamus (PVH). Nevertheless, the circuitry underlying BST control over the stress axis and its role in depression-related behaviors has remained obscure. Utilizing optogenetic approaches in rats, we have identified a novel role for the anteroventral subdivision of BST in the coordinated inhibition of both HPA output and passive coping behaviors during acute inescapable (tail suspension, TS) stress. Follow-up experiments probed axonal pathways emanating from the anteroventral BST which accounted for separable endocrine and behavioral functions subserved by this cell group. The PVH and ventrolateral periaqueductal gray were recipients of GABAergic outputs from the anteroventral BST that were necessary to restrain stress-induced HPA activation and passive coping behavior, respectively, during TS and forced swim tests. In contrast to other BST subdivisions implicated in anxiety-like responses, these results direct attention to the anteroventral BST as a nodal point in a stress-modulatory network for coordinating neuroendocrine and behavioral coping responses, wherein impairment could account for core features of stress-related mood disorders. SIGNIFICANCE STATEMENT Dysregulation of the neural pathways modulating stress-adaptive behaviors is implicated in stress-related psychiatric illness. While aversive situations activate a network of limbic forebrain regions thought to mediate such changes, little is known about how this information is integrated to orchestrate complex stress responses. Here we identify novel roles for the anteroventral bed nuclei of the stria terminalis in inhibiting both stress hormone output and passive coping behavior via divergent projections to regions of the hypothalamus and midbrain. Inhibition of these projections

  12. Protective role of misoprostol against cisplatin-induced ototoxicity.

    PubMed

    Doğan, Murat; Polat, Halil; Yaşar, Mehmet; Kaya, Altan; Bayram, Ali; Şenel, Fatma; Özcan, İbrahim

    2016-11-01

    Cis-diammineedichloroplatinum (cisplatin) is a chemotherapeutic agent that is widely used in the treatment of many cancers. Nephrotoxicity, ototoxicity and neurotoxicity are dose-limiting adverse effects for cisplatin. The cellular and molecular mechanisms underlying cisplatin-induced ototoxicity aren't fully understood. It has been proposed that cisplatin primarily cause damage at the cochlea, outer hair cells in particular, leading to excessive production of free oxygen radicals in the organ of Corti, stria vascularis, spiral ligament, and spiral ganglionic cells. The cytotoxicity is associated with the generation of reactive oxygen species (ROS); thus, there is an increasing interest on antioxidants with an effort to discover the established protection against cisplatin-induced ototoxicity over time. Misoprostol (MP) has gained considerable interest as a reactive oxygen species scavenger in recent years. To best of our knowledge, there is no study about protective effect of MP, a prostaglandin E1 (PGE1) analogue, on cisplatin-induced ototoxicity. In our study, we show that protective effects of misoprostol on cisplatin-induced ototoxcity on rats.

  13. The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss.

    PubMed

    Yoo, T J; Du, Xiaoping; Zhou, Bin

    2015-12-01

    The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4(+)CD25(+)Foxp3(+)T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally.

  14. Inhibitors of Histone Deacetylases Attenuate Noise-Induced Hearing Loss.

    PubMed

    Chen, Jun; Hill, Kayla; Sha, Su-Hua

    2016-08-01

    Loss of auditory sensory hair cells is the major pathological feature of noise-induced hearing loss (NIHL). Currently, no established clinical therapies for prevention or amelioration of NIHL are available. The absence of treatments is due to our lack of a comprehensive understanding of the molecular mechanisms underlying noise-induced damage. Our previous study indicates that epigenetic modification of histones alters hair cell survival. In this study, we investigated the effect of noise exposure on histone H3 lysine 9 acetylation (H3K9ac) in the inner ear of adult CBA/J mice and determined if inhibition of histone deacetylases by systemic administration of suberoylanilide hydroxamic acid (SAHA) could attenuate NIHL. Our results showed that H3K9ac was decreased in the nuclei of outer hair cells (OHCs) and marginal cells of the stria vascularis in the basal region after exposure to a traumatic noise paradigm known to induce permanent threshold shifts (PTS). Consistent with these results, levels of histone deacetylases 1, 2, and 3 (HDAC1, HDAC2 and HDAC3) were increased predominately in the nuclei of cochlear cells. Silencing of HDAC1, HDAC2, or HDAC3 with siRNA reduced the expression of the target HDAC in OHCs, but did not attenuate noise-induced PTS, whereas treatment with the pan-HDAC inhibitor SAHA, also named vorinostat, reduced OHC loss, and attenuated PTS. These findings suggest that histone acetylation is involved in the pathogenesis of noise-induced OHC death and hearing loss. Pharmacological targeting of histone deacetylases may afford a strategy for protection against NIHL.

  15. Projections from the anteroventral part of the medial amygdaloid nucleus in the rat.

    PubMed

    Novaes, Leonardo S; Shammah-Lagnado, Sara J

    2011-11-03

    The medial amygdaloid nucleus (Me) integrates pheromonal and olfactory information with gonadal hormone cues, being implicated in social behaviors. It is divided cytoarchitectonically in an anterodorsal, anteroventral (MeAV), posterodorsal and posteroventral part, whose projections are well characterized, except for those of the tiny MeAV. Here, MeAV efferents were examined in the rat with the anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde Fluoro-Gold (FG) tracers and compared with those of other Me parts. The present PHA-L observations show that the MeAV projects profusely to itself, but its projections to other Me parts are modest. In conjunction with FG experiments, they suggest that the MeAV innervates robustly a restricted set of structures it shares with the anterodorsal and/or posteroventral Me. Its major targets are the core of the ventromedial hypothalamic nucleus (especially the dorsomedial and central parts), reached mainly via the stria terminalis, and the amygdalostriatal transition area. In addition, the MeAV innervates substantially the lateral and posterior basomedial amygdaloid nuclei and the intraamygdaloid bed nucleus of the stria terminalis. In contrast to other Me parts, it provides only modest inputs to the main and accessory olfactory systems, medial bed nucleus of the stria terminalis and reproductive hypothalamic nuclei. This anatomical framework suggests that the MeAV may play a role in orienting responses to chemosensory cues and defensive behaviors elicited by the odor of predators.

  16. Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder

    PubMed Central

    Kennis, Mitzy; van Rooij, Sanne J H; Tromp, Do P M; Fox, Andrew S; Rademaker, Arthur R; Kahn, René S; Kalin, Ned H; Geuze, Elbert

    2015-01-01

    Posttraumatic stress disorder (PTSD) is a debilitating disorder that has been associated with brain abnormalities, including white matter alterations. However, little is known about the effect of treatment on these brain alterations. To investigate the course of white matter alterations in PTSD, we used a longitudinal design investigating treatment effects on white matter integrity using diffusion tensor imaging (DTI). Diffusion tensor and magnetization transfer images were obtained pre- and posttreatment from veterans with (n=39) and without PTSD (n=22). After treatment, 16 PTSD patients were remitted, and 23 had persistent PTSD based on PTSD diagnosis. The dorsal and hippocampal cingulum bundle, stria terminalis, and fornix were investigated as regions of interest. Exploratory whole-brain analyses were also performed. Groups were compared with repeated-measures ANOVA for fractional anisotropy (FA), and magnetization transfer ratio. Persistently symptomatic PTSD patients had increasing FA of the dorsal cingulum over time, and at reassessment these FA values were higher than both combat controls and the remitted PTSD group. Group-by-time interactions for FA were found in the hippocampal cingulum, fornix, and stria terminalis, posterior corona radiata, and superior longitudinal fasciculus. Our results indicate that higher FA of the dorsal cingulum bundle may be an acquired feature of persistent PTSD that develops over time. Furthermore, treatment might have differential effects on the hippocampal cingulum, fornix, stria terminalis, posterior corona radiata, and superior longitudinal fasciculus in remitted vs persistent PTSD patients. This study contributes to a better understanding of the neural underpinnings of PTSD treatment outcome. PMID:25837284

  17. Cadmium and naphthalene-induced hyperglycemia in the fiddler crab, Uca pugilator: Differential modes of action on the neutroendocrine system

    SciTech Connect

    Reddy, P.S.; Katyayani, R.V.; Fingerman, M.

    1996-03-01

    Hyperglycemia is a typical response of aquatic organisms to heavy metals. In crustaceans, the medulla terminalis X-organ-sinus gland neuroendocrine complex in the eyestalk is the source of the crustacean hyperglycemic hormone (CHH). The role of CHH in pollutant-induced b1ood glucose changes has only recently begun to be studied. Reddy provided evidence that CHH mediates cadmium-induced hyperglycemia in the red swamp crayfish, Procambarus clarkii. In a study of another hormonally-regulated function, color changes, cadmium exposure resulted in pigment in the melanophores of the fiddler crab, Uca pugilator, becoming less dispersed than in unexposed crabs. Earlier studies showed that, like cadmium, both a PCB, Aroclor 1242, and naphthalene induced black pigment aggregation in Uca poor. In general, when crabs are exposed to a pollutant, hydrocarbon or cadmium, they aggregate the pigment in their melanophores, but apparently by different mechanisms. Hydrocarbons appear to inhibit release of black pigment-dispersing hormone (BDPH), whereas cadmium appears to inhibit its synthesis. These apparent different modes of action of cadmium and naphthalene on the color change mechanism led us to compare the impact of these pollutants on the hormonal regulation of blood glucose in Uca pugilator. The present study was performed to determine (1) whether cadmium and naphthalene induce hyperglycemia in Uca pugilator, (2) whether CH has a role, if naphthalene and cadmium do induce hyperglycemia, and (3) the effects, if any, of cadmium and naphthalene on CHH activity in the eyestalk neuroendocrine complex.

  18. Neurotoxicity of ecstasy (MDMA): an overview.

    PubMed

    Sarkar, Sumit; Schmued, Larry

    2010-08-01

    "Ecstasy" (MDMA) is a powerful hallucinogenic drug which has raised concern worldwide because of its high abuse liability. A plethora of studies have demonstrated that MDMA has the potential to induce neurotoxicity both in human and laboratory animals. Although research on MDMA has been carried out by many different laboratories, the mechanism underlying MDMA induced toxicity has not been fully elucidated. MDMA has the ability to reduce serotonin levels in terminals of axons in the cortex of rats and mice. Recently we have shown that it also has the potential to produce degenerate neurons in discrete areas of the brain such as insular and parietal cortex, thalamus, tenia tecta and bed nucleus of stria terminalis (BST). Acute effects of MDMA can result in a constellation of changes including arrthymias, hypertension, hyperthermia, serotonin (5-HT) syndrome, liver problems, seizures and also long lasting neurocognitive impairments including mood disturbances. In human MDMA abusers, there is evidence for reduction of serotonergic biochemical markers. Several factors may contribute to the MDMA-induced neurotoxicity, especially hyperthermia. Other factors potentially influencing MDMA toxicity include monoamine oxidase metabolism of dopamine and serotonin, nitric oxide generation, glutamate excitotoxicity, serotonin 2A receptor agonism and the formation of MDMA neurotoxic metabolites. In this review we will cover the following topics: pharmacological mechanisms, metabolic pathways and acute effects in laboratory animals, as well as in humans, with special attention on the mechanism and pathology of MDMA induced neurotoxicity.

  19. Effects of ozone (O3) therapy on cisplatin-induced ototoxicity in rats.

    PubMed

    Koçak, Hasan Emre; Taşkın, Ümit; Aydın, Salih; Oktay, Mehmet Faruk; Altınay, Serdar; Çelik, Duygu Sultan; Yücebaş, Kadir; Altaş, Bengül

    2016-12-01

    The aim of this study is to investigate the effect of rectal ozone and intratympanic ozone therapy on cisplatin-induced ototoxicity in rats. Eighteen female Wistar albino rats were included in our study. External auditory canal and tympanic membrane examinations were normal in all rats. The rats were randomly divided into three groups. Initially, all the rats were tested with distortion product otoacoustic emissions (DPOAE), and emissions were measured normally. All rats were injected with 5-mg/kg/day cisplatin for 3 days intraperitoneally. Ototoxicy had developed in all rats, as confirmed with DPOAE after 1 week. Rectal and intratympanic ozone therapy group was Group 1. No treatment was administered for the rats in Group 2 as the control group. The rats in Group 3 were treated with rectal ozone. All the rats were tested with DPOAE under general anesthesia, and all were sacrificed for pathological examination 1 week after ozone administration. Their cochleas were removed. The outer hair cell damage and stria vascularis damage were examined. In the statistical analysis conducted, a statistically significant difference between Group 1 and Group 2 was observed in all frequencies according to the DPOAE test. In addition, between Group 2 and Group 3, a statistically significant difference was observed in the DPOAE test. However, a statistically significant difference was not observed between Group 1 and Group 3 according to the DPOAE test. According to histopathological scoring, the outer hair cell damage score was statistically significantly high in Group 2 compared with Group 1. In addition, the outer hair cell damage score was also statistically significantly high in Group 2 compared with Group 3. Outer hair cell damage scores were low in Group 1 and Group 3, but there was no statistically significant difference between these groups. There was no statistically significant difference between the groups in terms of stria vascularis damage score examinations

  20. Role of the copper transporter, CTR1, in platinum-induced ototoxicity.

    PubMed

    More, Swati S; Akil, Omar; Ianculescu, Alexandra G; Geier, Ethan G; Lustig, Lawrence R; Giacomini, Kathleen M

    2010-07-14

    The goal of this study was to determine the role of an influx copper transporter, CTR1, in the ototoxicity induced by cisplatin, a potent anticancer platinum analog used in the treatment of a variety of solid tumors. As determined through reverse transcriptase-PCR (RT-PCR), quantitative RT-PCR, Western blot, and immunohistochemistry, mouse CTR1 (Ctr1) was found to be abundantly expressed and highly localized at the primary sites of cisplatin toxicity in the inner ear, mainly outer hair cells (OHCs), inner hair cells, stria vascularis, spiral ganglia, and surrounding nerves in the mouse cochlea. A CTR1 substrate, copper sulfate, decreased the uptake and cytotoxicity of cisplatin in HEI-OC1, a cell line that expresses many molecular markers reminiscent of OHCs. Small interfering RNA-mediated knockdown of Ctr1 in this cell line caused a corresponding decrease in cisplatin uptake. In mice, intratympanic administration of copper sulfate 30 min before intraperitoneal administration of cisplatin was found to prevent hearing loss at click stimulus and 8, 16, and 32 kHz frequencies. To date, the utility of cisplatin remains severely limited because of its ototoxic effects. The studies described in this report suggest that cisplatin-induced ototoxicity and cochlear uptake can be modulated by administration of a CTR1 inhibitor, copper sulfate. The possibility of local administration of CTR1 inhibitors during cisplatin therapy as a means of otoprotection is thereby raised.

  1. Effects of repeated tianeptine treatment on CRF mRNA expression in non-stressed and chronic mild stress-exposed rats.

    PubMed

    Kim, Sung-Jin; Park, Sang-Ha; Choi, Song-Hyen; Moon, Bo-Hyun; Lee, Kuem-Ju; Kang, Seung Woo; Lee, Min-Soo; Choi, Sang-Hyun; Chun, Boe-Gwun; Shin, Kyung-Ho

    2006-06-01

    Accumulating evidence suggests that dysregulation of corticotropin-releasing factor (CRF) may play a role in depression and that this dysregulation may be corrected by antidepressant drug treatment. Here, we examined whether chronic mild stress (CMS) alters CRF mRNA levels in stress-related brain areas including the bed nucleus of the stria terminalis (BNST) and the central nucleus of amygdala (CeA), and whether repeated tianeptine treatment can attenuate CMS-induced changes in CRF mRNA levels. Male rats were exposed to CMS for 19 days, and control animals were subjected to brief handling. Both groups were injected daily with tianeptine or saline. CMS significantly increased CRF mRNA levels in the dorsal BNST (dBNST), but not in other areas. Repeated tianeptine treatment prevented the CMS-induced increase in CRF mRNA levels in the dBNST, and reduced CRF mRNA levels in dBNST in non-stressed controls. Moreover, repeated tianeptine treatment significantly decreased CRF mRNA levels in the ventral BNST and CeA of non-stressed controls as well as CMS-exposed rats. These results show that CMS induces a rather selective increase of CRF mRNA in the dBNST. In addition, these results suggest that repeated tianeptine treatment diminishes the basal activity of CRF neurons and reduces their sensitivity to stress.

  2. Mesolimbic neuropeptide W coordinates stress responses under novel environments.

    PubMed

    Motoike, Toshiyuki; Long, Jeffrey M; Tanaka, Hirokazu; Sinton, Christopher M; Skach, Amber; Williams, S Clay; Hammer, Robert E; Sakurai, Takeshi; Yanagisawa, Masashi

    2016-05-24

    Neuropeptide B (NPB) and neuropeptide W (NPW) are endogenous neuropeptide ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimbic region possess tyrosine hydroxylase immunoreactivity, indicating that a small subset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limbic system nuclei in adult mouse brain: the lateral bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhibition of cellular activity, but this stress-induced inhibition was attenuated in the CeAL neurons of NPW(-/-) mice. Moreover, the response of NPW(-/-) mice to either formalin-induced pain stimuli or a live rat (i.e., a potential predator) was abnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the behavior of NPW(-/-) mice in a habituated environment was indistinguishable from that of wild-type mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments.

  3. Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women

    PubMed Central

    de Jong, Peter J.; Georgiadis, Janniko R.

    2014-01-01

    Lifetime experiences shape people’s attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile–vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-‘hot’ vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-‘hot’) associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli. PMID:23051899

  4. Analysis of behavioral constraints and the neuroanatomy of fear to the predator odor trimethylthiazoline: a model for animal phobias.

    PubMed

    Rosen, Jeffrey B; Pagani, Jerome H; Rolla, Katherine L G; Davis, Cameron

    2008-09-01

    Specific phobias, including animal phobias, are the most common anxiety disorders, and have a strong innate and genetic component. Research on the neurobiology and environmental constraints of innate fear of predators in rodents may be useful in elucidating mechanisms of animal phobias in humans. The present article reviews research on innate fear in rats to trimethylthiazoline (TMT), an odor originally isolated from fox feces. TMT induces unconditioned freezing and other defensive responses that are regulated by the dose of TMT and the shape of the testing environment. Contextual conditioning induced by TMT occurs, but is constrained by the environment. Lesion studies indicate the amygdala circuitry subserving fear conditioning is not necessary for unconditioned fear to TMT. Additionally, a medial hypothalamic defensive circuit also appears not necessary for unconditioned freezing to TMT, whereas circuits that include the medial nucleus of the amygdala and the bed nucleus of the stria terminalis are essential. The importance of these findings of innate predator odor fear in rodents to animal phobias in humans is discussed.

  5. Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women.

    PubMed

    Borg, Charmaine; de Jong, Peter J; Georgiadis, Janniko R

    2014-02-01

    Lifetime experiences shape people's attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile-vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-'hot' vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-'hot') associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli.

  6. Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes.

    PubMed

    De Luca, Laurival A; Xu, Zhice; Schoorlemmer, Guus H M; Thunhorst, Robert L; Beltz, Terry G; Menani, José V; Johnson, Alan Kim

    2002-02-01

    Adult rats deprived of water for 24-30 h were allowed to rehydrate by ingesting only water for 1-2 h. Rats were then given access to both water and 1.8% NaCl. This procedure induced a sodium appetite defined by the operational criteria of a significant increase in 1.8% NaCl intake (3.8 +/- 0.8 ml/2 h; n = 6). Expression of Fos (as assessed by immunohistochemistry) was increased in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), and supraoptic nucleus (SON) after water deprivation. After rehydration with water but before consumption of 1.8% NaCl, Fos expression in the SON disappeared and was partially reduced in the OVLT and MnPO. However, Fos expression did not change in the SFO. Water deprivation also 1) increased plasma renin activity (PRA), osmolality, and plasma Na+; 2) decreased blood volume; and 3) reduced total body Na+; but 4) did not alter arterial blood pressure. Rehydration with water alone caused only plasma osmolality and plasma Na+ concentration to revert to euhydrated levels. The changes in Fos expression and PRA are consistent with a proposed role for ANG II in the control of the sodium appetite produced by water deprivation followed by rehydration with only water.

  7. Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes

    NASA Technical Reports Server (NTRS)

    De Luca, Laurival A Jr; Xu, Zhice; Schoorlemmer, Guus H M.; Thunhorst, Robert L.; Beltz, Terry G.; Menani, Jose V.; Johnson, Alan Kim

    2002-01-01

    Adult rats deprived of water for 24-30 h were allowed to rehydrate by ingesting only water for 1-2 h. Rats were then given access to both water and 1.8% NaCl. This procedure induced a sodium appetite defined by the operational criteria of a significant increase in 1.8% NaCl intake (3.8 +/- 0.8 ml/2 h; n = 6). Expression of Fos (as assessed by immunohistochemistry) was increased in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), and supraoptic nucleus (SON) after water deprivation. After rehydration with water but before consumption of 1.8% NaCl, Fos expression in the SON disappeared and was partially reduced in the OVLT and MnPO. However, Fos expression did not change in the SFO. Water deprivation also 1) increased plasma renin activity (PRA), osmolality, and plasma Na+; 2) decreased blood volume; and 3) reduced total body Na+; but 4) did not alter arterial blood pressure. Rehydration with water alone caused only plasma osmolality and plasma Na+ concentration to revert to euhydrated levels. The changes in Fos expression and PRA are consistent with a proposed role for ANG II in the control of the sodium appetite produced by water deprivation followed by rehydration with only water.

  8. Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

    PubMed Central

    Li, Jian-Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yu-Ping; Fang, Zhi-Qin; Sun, Hong-Sheng; Peng, Wei; Zhang, Jin-Shun

    2016-01-01

    Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD. PMID:27746855

  9. Modulation of nucleus accumbens connectivity by alcohol drinking and naltrexone in alcohol-preferring rats: A manganese-enhanced magnetic resonance imaging study.

    PubMed

    Dudek, Mateusz; Canals, Santiago; Sommer, Wolfgang H; Hyytiä, Petri

    2016-03-01

    The nonselective opioid receptor antagonist naltrexone is now used for the treatment of alcoholism, yet naltrexone's central mechanism of action remains poorly understood. One line of evidence suggests that opioid antagonists regulate alcohol drinking through interaction with the mesolimbic dopamine system. Hence, our goal here was to examine the role of the nucleus accumbens connectivity in alcohol reinforcement and naltrexone's actions using manganese-enhanced magnetic resonance imaging (MEMRI). Following long-term free-choice drinking of alcohol and water, AA (Alko Alcohol) rats received injections of MnCl2 into the nucleus accumbens for activity-dependent tracing of accumbal connections. Immediately after the accumbal injections, rats were imaged using MEMRI, and then allowed to drink either alcohol or water for the next 24h. Naltrexone was administered prior to the active dark period, and the second MEMRI was performed 24h after the first scan. Comparison of signal intensity at 1 and 24h after accumbal MnCl2 injections revealed an ipsilateral continuum through the ventral pallidum, bed nucleus of the stria terminalis, globus pallidus, and lateral hypothalamus to the substantia nigra and ventral tegmental area. Activation was also seen in the rostral part of the insular cortex and regions of the prefrontal cortex. Alcohol drinking resulted in enhanced activation of these connections, whereas naltrexone suppressed alcohol-induced activity. These data support the involvement of the accumbal connections in alcohol reinforcement and mediation of naltrexone's suppressive effects on alcohol drinking through their deactivation.

  10. Social defeat stress potentiates thermal sensitivity in operant models of pain processing

    PubMed Central

    Marcinkiewcz, Catherine A.; Green, Megan K.; Devine, Darragh P.; Duarte, Peter; Vierck, Charles J.; Yezierski, Robert P.

    2013-01-01

    Higher-order processing of nociceptive input is distributed in corticolimbic regions of the brain, including the anterior cingulate, parieto-insular and prefrontal cortices, as well as subcortical structures such as the bed nucleus of stria terminalis and amygdala. In addition to their role in pain processing, these regions encode or modulate emotional, motivational and sensory responses to stress. Thus, pain and stress pathways in the brain intersect at cortical and subcortical forebrain structures. Accordingly, previous work has shown that acute restraint stress in female rats induces heat hyperalgesia in a forebrain-dependent operant test of thermal escape. In the present study, we investigated the effects of social defeat stress in male rats on the operant escape task, as well as in a test of nociceptive thermal preference. After establishing baseline behaviors in these tests, separate groups of rats were socially defeated by dominant “resident” male rats. They were tested for thermal preference after 5 successive social defeat sessions. Escape from cold, heat and a neutral warm temperature also was evaluated after social defeat. Defeated rats exhibited a significant increase in cold preference after social defeat compared to the baseline. In the escape task, the rats exhibited increased escape from warm and nociceptive cold and heat temperatures. Thus, chronic social stress produces hyperalgesia for both hot and cold stimuli in male rats, suggesting a mutually facilitatory cross-regulation between central pathways regulating stress and pain. PMID:19059227

  11. Dopamine D2 receptors gate generalization of conditioned threat responses through mTORC1 signaling in the extended amygdala

    PubMed Central

    De Bundel, Dimitri; Zussy, Charleine; Espallergues, Julie; Gerfen, Charles R; Girault, Jean-Antoine; Valjent, Emmanuel

    2016-01-01

    Overgeneralization of conditioned threat responses is a robust clinical marker of anxiety disorders. In overgeneralization, responses that are appropriate to threat-predicting cues are evoked by perceptually similar safety-predicting cues. Inappropriate learning of conditioned threat responses may thus form an etiological basis for anxiety disorders. The role of dopamine (DA) in memory encoding is well established. Indeed by signaling salience and valence, DA is thought to facilitate discriminative learning between stimuli representing safety or threat. However, the neuroanatomical and biochemical substrates through which DA modulates overgeneralization of threat responses remain poorly understood. Here we report that the modulation of DA D2 receptor (D2R) signaling bidirectionally regulates the consolidation of fear responses. While the blockade of D2R induces generalized fear responses, its stimulation facilitates discriminative learning between stimuli representing safety or threat. Moreover, we show that controlled fear generalization requires the coordinated activation of D2R in the bed nucleus of the stria terminalis (BNST) and the central amygdala (CEA). Finally, we identify the mTORC1 cascade activation as an important molecular event by which D2R mediates its effects. These data reveal that D2R signaling in the extended amygdala constitutes an important checkpoint through which DA participates in the control of threat processing and the emergence of overgeneralized fear responses. PMID:26782052

  12. Reward deficiency and anti-reward in pain chronification.

    PubMed

    Borsook, D; Linnman, C; Faria, V; Strassman, A M; Becerra, L; Elman, I

    2016-09-01

    Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification).

  13. Functional identification of a neurocircuit regulating blood glucose

    PubMed Central

    Meek, Thomas H.; Nelson, Jarrell T.; Matsen, Miles E.; Dorfman, Mauricio D.; Guyenet, Stephan J.; Damian, Vincent; Allison, Margaret B.; Scarlett, Jarrad M.; Nguyen, Hong T.; Thaler, Joshua P.; Olson, David P.; Myers, Martin G.; Schwartz, Michael W.; Morton, Gregory J.

    2016-01-01

    Previous studies implicate the hypothalamic ventromedial nucleus (VMN) in glycemic control. Here, we report that selective inhibition of the subset of VMN neurons that express the transcription factor steroidogenic-factor 1 (VMNSF1 neurons) blocks recovery from insulin-induced hypoglycemia whereas, conversely, activation of VMNSF1 neurons causes diabetes-range hyperglycemia. Moreover, this hyperglycemic response is reproduced by selective activation of VMNSF1 fibers projecting to the anterior bed nucleus of the stria terminalis (aBNST), but not to other brain areas innervated by VMNSF1 neurons. We also report that neurons in the lateral parabrachial nucleus (LPBN), a brain area that is also implicated in the response to hypoglycemia, make synaptic connections with the specific subset of glucoregulatory VMNSF1 neurons that project to the aBNST. These results collectively establish a physiological role in glucose homeostasis for VMNSF1 neurons and suggest that these neurons are part of an ascending glucoregulatory LPBN→VMNSF1→aBNST neurocircuit. PMID:27001850

  14. Orexin administration to mice that underwent chronic stress produces bimodal effects on emotion-related behaviors.

    PubMed

    Chung, Hye-Seung; Kim, Jae-Gon; Kim, Jae-Won; Kim, Hyung-Wook; Yoon, Bong-June

    2014-11-01

    Orexin plays diverse roles in regulating behaviors, such as sleep and wake, reward processing, arousal, and stress and anxiety. The orexin system may accomplish these multiple tasks through its complex innervations throughout the brain. The emerging evidence indicates a role of orexin in emotional behaviors; however, most of the previous studies have investigated the function of orexin in naïve animals. Here, we examined a functional role of orexin in mice that had been exposed to repeated stress. Chronic social defeat stress produced differential social interaction behaviors in mice (susceptible versus resilient) and these two groups of mice displayed different levels of prepro-orexin in the hypothalamus. Exogenously added orexin A to the brain induced an antidepressant-like effect in only the susceptible mice but not in the resilient mice. In contrast, orexin A and orexin B infused together produced an anxiogenic effect in only the resilient mice and not in the susceptible mice. Furthermore, we found that the antidepressant-like effect of orexin A is mediated by the bed nucleus of the stria terminalis (BNST) after exposure to chronic restraint stress. These findings reveal a bimodal effect of the orexin system in regulating emotional behavior that depends on stress susceptibility.

  15. AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.

    PubMed

    Steculorum, Sophie M; Ruud, Johan; Karakasilioti, Ismene; Backes, Heiko; Engström Ruud, Linda; Timper, Katharina; Hess, Martin E; Tsaousidou, Eva; Mauer, Jan; Vogt, Merly C; Paeger, Lars; Bremser, Stephan; Klein, Andreas C; Morgan, Donald A; Frommolt, Peter; Brinkkötter, Paul T; Hammerschmidt, Philipp; Benzing, Thomas; Rahmouni, Kamal; Wunderlich, F Thomas; Kloppenburg, Peter; Brüning, Jens C

    2016-03-24

    Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis.

  16. Physical interaction is not necessary for the induction of housing-type social buffering of conditioned hyperthermia in male rats.

    PubMed

    Kiyokawa, Yasushi; Kodama, Yuka; Takeuchi, Yukari; Mori, Yuji

    2013-11-01

    In social animals, housing with conspecific animals after a stressful event attenuates the subsequent adverse outcomes due to the event, and this has been called housing-type social buffering. We have previously found that housing-type social buffering attenuates the enhancement of hyperthermia and Fos expression in the paraventricular nucleus of the hypothalamus that occurs in response to an aversive conditioned stimulus in male rats. Here, we analyzed the role of physical interactions during social housing in the induction of housing-type social buffering. When a fear-conditioned subject was alone after the conditioning and then exposed to the conditioned stimulus, it showed behavioral, autonomic, and neural stress responses. However, social housing, during which physical interactions were prevented by wire mesh, attenuated these autonomic and neural stress responses, as has been seen in previous studies. These results suggested that physical interaction was not necessary for the induction of housing-type social buffering. With this social cohabitation model, we then found that social cohabitation increased Fos expression in the posterior complex of the anterior olfactory nucleus of the fear-conditioned subject. Social cohabitation also increased Fos expression in 11 brain regions, including the prefrontal cortex, the nucleus accumbens, the bed nucleus of the stria terminalis, and the medial, lateral, basal, and cortical amygdala. These results provide information about the neural mechanisms that induce housing-type social buffering.

  17. Revisiting the neural role of estrogen receptor beta in male sexual behavior by conditional mutagenesis.

    PubMed

    Naulé, Lydie; Marie-Luce, Clarisse; Parmentier, Caroline; Martini, Mariangela; Albac, Christelle; Trouillet, Anne-Charlotte; Keller, Matthieu; Hardin-Pouzet, Hélène; Mhaouty-Kodja, Sakina

    2016-04-01

    Estradiol derived from neural aromatization of gonadal testosterone plays a key role in the perinatal organization of the neural circuitry underlying male sexual behavior. The aim of this study was to investigate the contribution of neural estrogen receptor (ER) β in estradiol-induced effects without interfering with its peripheral functions. For this purpose, male mice lacking ERβ in the nervous system were generated. Analyses of males in two consecutive tests with a time interval of two weeks showed an effect of experience, but not of genotype, on the latencies to the first mount, intromission, pelvic thrusting and ejaculation. Similarly, there was an effect of experience, but not of genotype, on the number of thrusts and mating length. Neural ERβ deletion had no effect on the ability of males to adopt a lordosis posture in response to male mounts, after castration and priming with estradiol and progesterone. Indeed, only low percentages of both genotypes exhibited a low lordosis quotient. It also did not affect their olfactory preference. Quantification of tyrosine hydroxylase- and kisspeptin-immunoreactive neurons in the preoptic area showed unaffected sexual dimorphism of both populations in mutants. By contrast, the number of androgen receptor- and ERα-immunoreactive cells was significantly increased in the bed nucleus of stria terminalis of mutant males. These data show that neural ERβ does not play a crucial role in the organization and activation of the neural circuitry underlying male sexual behavior. These discrepancies with the phenotype of global ERβ knockout models are discussed.

  18. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala

    PubMed Central

    D’Agostino, Giuseppe; Halladay, Lindsay R.; Hardaway, J. Andrew; DiBerto, Jeffrey F.; Navarro, Montserrat; Burnham, Nathan; Cristiano, Claudia; Dorrier, Cayce E.; Tipton, Gregory J.; Ramakrishnan, Charu; Kozicz, Tamas; Deisseroth, Karl; Thiele, Todd E.; McElligott, Zoe A.; Holmes, Andrew; Heisler, Lora K.; Kash, Thomas L.

    2016-01-01

    Summary paragraph Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter that has an essential role in the regulation of emotion. The precise circuits through which aversive states are orchestrated by 5-HT, however, have not yet been defined. Here we show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety and activates a subpopulation of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis (CRFBNST). Specifically, 5-HTDRN projections to the BNST, via actions at 5-HT2C receptors (5-HT2CRs), engage a CRFBNST inhibitory microcircuit that silences anxiolytic BNST outputs to the ventral tegmental area (VTA) and lateral hypothalamus (LH). Further, we demonstrate that this CRFBNST inhibitory circuit underlies aversive behavior following acute exposure to selective serotonin reuptake inhibitors (SSRIs). This early aversive effect is mediated via the corticotrophin releasing factor type 1 receptor (CRF1R) given that CRF1R antagonism is sufficient to prevent acute SSRI-induced enhancements in aversive learning. These results reveal an essential 5-HTDRN→CRFBNST circuit governing fear and anxiety and provide a potential mechanistic explanation for the clinical observation of early adverse events to SSRI treatment in some patients with anxiety disorders1,2. PMID:27556938

  19. Quantitative autoradiography of /sup 3/H-nomifensine binding sites in rat brain

    SciTech Connect

    Scatton, B.; Dubois, A.; Dubocovich, M.L.; Zahniser, N.R.; Fage, D.

    1985-03-04

    The distribution of /sup 3/H-nomifensine binding sites in the rat brain has been studied by quantitative autoradiography. The binding of /sup 3/H-nomifensine to caudate putamen sections was saturable, specific, of a highly affinity (Kd = 56 nM) and sodium-dependent. The dopamine uptake inhibitors benztropine, nomifensine, cocaine, bupropion and amfonelic acid were the most potent competitors of /sup 3/H-nomifensine binding to striatal sections. The highest levels of (benztropine-displaceable) /sup 3/H-nomifensine binding sites were found in the caudate-putamen, the olfactory tubercle and the nucleus accumbens. 6-Hydroxy-dopamine-induced lesion of the ascending dopaminergic bundle resulted in a marked decrease in the /sup 3/H-ligand binding in these areas. Moderately high concentrations of the /sup 3/H-ligand were observed in the bed nucleus of the stria terminalis, the anteroventral thalamic nucleus, the cingulate cortex, the lateral septum, the hippocampus, the amygdala, the zona incerta and some hypothalamic nuclei. There were low levels of binding sites in the habenula, the dorsolateral geniculate body, the substantia nigra, the ventral tegmental area and the periaqueductal gray matter. These autoradiographic data are consistent with the hypothesis that /sup 3/H-nomifensine binds primarily to the presynaptic uptake site for dopamine but also labels the norepinephrine uptake site. 33 references, 2 figures, 1 table.

  20. Induced Abortion

    MedlinePlus

    ... Education & Events Advocacy For Patients About ACOG Induced Abortion Home For Patients Search FAQs Induced Abortion Page ... Induced Abortion FAQ043, May 2015 PDF Format Induced Abortion Special Procedures What is an induced abortion? What ...

  1. Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria.

    PubMed

    Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

    2013-09-01

    Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche-Ramirez-Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca(2+) handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate

  2. Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography

    PubMed Central

    Koller, Kristin; Bultitude, Janet H.; Mullins, Paul; Ward, Robert; Mitchell, Anna S.; Bell, Andrew H.

    2015-01-01

    It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species. PMID:26224780

  3. Mitochondrial DNA common deletion increases susceptibility to noise-induced hearing loss in a mimetic aging rat model.

    PubMed

    Yu, Jintao; Wang, Yanjun; Liu, Peng; Li, Qingyu; Sun, Yu; Kong, Weijia

    2014-10-24

    Noise-induced hearing loss (NIHL) is an important occupational health hazard. However, susceptibility to NIHL remains poorly understood. The present study was designed to investigate whether mitochondrial DNA common deletion (CD) increases the susceptibility of individuals to NIHL. A mimetic aging rat model harboring increased CD in the inner ear was established by chronic d-galactose administration, and the synergic effect of CD and noise on hearing sensitivity was assessed. We determined that although developed the same magnitude of temporary threshold shifts and hair cell loss, the d-galactose treated rats with increased CD in the inner ear exhibited a longer hearing recovery process and experienced higher permanent hearing threshold shifts at high frequencies than the saline-treated control rats. Greater supporting cell damage and stria vascularis ultrastructural changes were observed in d-galactose treated rats three weeks after recovery. The results suggested that the elevated CD in the inner ear could increase an individual's susceptibility to NIHL, which likely through a reduction in the self-repairing capability within the cochlea after acoustic injury.

  4. Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit.

    PubMed

    Pina, Melanie M; Cunningham, Christopher L

    2017-01-01

    Abstinent alcohol-dependent individuals experience an enduring sensitivity to cue-induced craving and relapse to drinking. There is considerable evidence indicating that structures within the midbrain and extended amygdala are involved in this process. Individually, the ventral tegmental area (VTA) and the bed nucleus of the stria terminalis (BNST) have been shown to modulate cue-induced ethanol-seeking behavior. It is hypothesized that cue-induced seeking is communicated through a direct projection from the BNST to VTA. In the current experiments, an intersectional viral strategy was used in DBA/2J mice to selectively target and inhibit BNST projections to the VTA during a test of ethanol conditioned place preference (CPP). Inhibitory designer receptors exclusively activated by designer drugs (hM4Di DREADDs) were expressed in VTA-projecting BNST (BNST-VTA) cells by infusing a retrograde herpes-simplex virus encoding cre recombinase (HSV-Cre) into VTA and a cre-inducible adeno-associated virus encoding hM4Di (AAV-DIO-hM4Di) into BNST. Before testing the expression of preference, clozapine-N-oxide (CNO) was peripherally administered to activate hM4Di receptors and selectively inhibit these cells. Ethanol CPP expression was blocked by CNO-mediated inhibition of BNST-VTA cells. A follow-up study revealed this effect was specific to CNO activation of hM4Di as saline- and CNO-treated mice infused with a control vector (HSV-GFP) in place of HSV-Cre showed significant CPP. These findings establish a role for a direct BNST input to VTA in cue-induced ethanol-seeking behavior.

  5. Estrogen regulation of the brain renin-angiotensin system in protection against angiotensin II-induced sensitization of hypertension.

    PubMed

    Xue, Baojian; Zhang, Zhongming; Beltz, Terry G; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2014-07-15

    This study investigated sex differences in the sensitization of angiotensin (ANG) II-induced hypertension and the role of central estrogen and ANG-(1-7) in this process. Male and female rats were implanted for telemetered blood pressure (BP) recording. A subcutaneous subpressor dose of ANG II was given alone or concurrently with intracerebroventricular estrogen, ANG-(1-7), an ANG-(1-7) receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and ovariectomized females, subpressor ANG II had no sustained effect on BP during induction, but produced an enhanced hypertensive response to the subsequent pressor dose of ANG II during expression. Central administration of estrogen or ANG-(1-7) during induction blocked ANG II-induced sensitization. In intact females, subpressor ANG II treatment produced a decrease in BP during induction and delay, and subsequent pressor ANG II treatment given during expression produced only a slight but significant increase in BP. However, central blockade of ANG-(1-7) by intracerebroventricular infusion of A-779 during induction restored the decreased BP observed in females during induction and enhanced the pressor response to the ANG II treatment during expression. RT-PCR analyses indicated that estrogen given during induction upregulated mRNA expression of the renin-angiotensin system (RAS) antihypertensive components, whereas both central estrogen and ANG-(1-7) downregulated mRNA expression of RAS hypertensive components in the lamina terminalis. The results indicate that females are protected from ANG II-induced sensitization through central estrogen and its regulation of brain RAS.

  6. Central endogenous angiotensin-(1-7) protects against aldosterone/NaCl-induced hypertension in female rats.

    PubMed

    Xue, Baojian; Zhang, Zhongming; Johnson, Ralph F; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2013-09-01

    In comparison to male rodents, females are protected against angiotensin (ANG) II- and aldosterone (Aldo)-induced hypertension. However, the mechanisms underlying this protective effect are not well understood. ANG-(1-7) is formed from ANG II by angiotensin-converting enzyme 2 (ACE2) and has an antihypertensive effect in the central nervous system (CNS). The present study tested the hypothesis that central ANG-(1-7) plays an important protective role in attenuating the development of Aldo/NaCl-hypertension in female rats. Systemic infusion of Aldo into intact female rats with 1% NaCl as their sole drinking fluid resulted in a slight increase in blood pressure (BP). Intracerebroventricular (icv) infusion of A-779, an ANG-(1-7) receptor (Mas-R) antagonist, significantly augmented the pressor effects of Aldo/NaCl. In contrast, systemic Aldo/NaCl induced a significant increase in BP in ovariectomized (OVX) female rats, and central infusion of ANG-(1-7) significantly attenuated this Aldo/NaCl pressor effect. The inhibitory effect of ANG-(1-7) on the Aldo/NaCl pressor effect was abolished by concurrent infusion of A-779. RT-PCR analyses showed that there was a corresponding change in mRNA expression of several renin-angiotensin system components, estrogen receptors and an NADPH oxidase subunit in the lamina terminalis. Taken together these results suggest that female sex hormones regulate an antihypertensive axis of the brain renin-angiotensin system involving ACE2/ANG-(1-7)/Mas-R that plays an important counterregulatory role in protecting against the development of Aldo/NaCl-induced hypertension.

  7. Central renin-angiotensin system activation and inflammation induced by high fat diet sensitize angiotensin II-elicited hypertension

    PubMed Central

    Xue, Baojian; Thunhorst, Robert L.; Yu, Yang; Guo, Fang; Beltz, Terry G.; Felder, Robert B.; Johnson, Alan Kim

    2016-01-01

    Obesity has been shown to promote renin-angiotensin system (RAS) activity and inflammation in the brain and to be accompanied by increased sympathetic activity and blood pressure (BP). Our previous studies demonstrated that administration of a subpressor dose of angiotensin (Ang) II sensitizes subsequent Ang II-elicited hypertension. The present study tested whether high fat diet (HFD) feeding also sensitizes the Ang II-elicited hypertensive response and whether HFD-induced sensitization is mediated by an increase in RAS activity and inflammatory mechanisms in the brain. HFD did not increase baseline BP, but enhanced the hypertensive response to Ang II compared to a normal fat diet. The sensitization produced by the HFD was abolished by concomitant central infusions of either a tumor necrosis factor α (TNF-α) synthesis inhibitor, pentoxifylline, an Ang II type 1 receptor (AT1-R) blocker, irbesartan or an inhibitor of microglial activation, minocycline. Furthermore, central pretreatment with TNF-α mimicked the sensitizing action of a central subpressor dose of Ang II, whereas central pentoxifylline or minocycline abolished this Ang II-induced sensitization. RT-PCR analysis of lamina terminalis tissue indicated that HFD feeding, central TNF-α or a central subpressor dose of Ang II upregulated mRNA expression of several components of the RAS and proinflammatory cytokines, whereas inhibition of AT1-R and of inflammation reversed these changes. The results suggest that HFD-induced sensitization of Ang II-elicited hypertension is mediated by upregulation of the brain RAS and of central proinflammatory cytokines. PMID:26573717

  8. Estrogen regulation of the brain renin-angiotensin system in protection against angiotensin II-induced sensitization of hypertension

    PubMed Central

    Zhang, Zhongming; Beltz, Terry G.; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2014-01-01

    This study investigated sex differences in the sensitization of angiotensin (ANG) II-induced hypertension and the role of central estrogen and ANG-(1–7) in this process. Male and female rats were implanted for telemetered blood pressure (BP) recording. A subcutaneous subpressor dose of ANG II was given alone or concurrently with intracerebroventricular estrogen, ANG-(1–7), an ANG-(1–7) receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and ovariectomized females, subpressor ANG II had no sustained effect on BP during induction, but produced an enhanced hypertensive response to the subsequent pressor dose of ANG II during expression. Central administration of estrogen or ANG-(1–7) during induction blocked ANG II-induced sensitization. In intact females, subpressor ANG II treatment produced a decrease in BP during induction and delay, and subsequent pressor ANG II treatment given during expression produced only a slight but significant increase in BP. However, central blockade of ANG-(1–7) by intracerebroventricular infusion of A-779 during induction restored the decreased BP observed in females during induction and enhanced the pressor response to the ANG II treatment during expression. RT-PCR analyses indicated that estrogen given during induction upregulated mRNA expression of the renin-angiotensin system (RAS) antihypertensive components, whereas both central estrogen and ANG-(1–7) downregulated mRNA expression of RAS hypertensive components in the lamina terminalis. The results indicate that females are protected from ANG II-induced sensitization through central estrogen and its regulation of brain RAS. PMID:24858844

  9. Localization and characterization of (/sup 3/H)desmethylimipramine binding sites in rat brain by quantitative autoradiography

    SciTech Connect

    Biegon, A.; Rainbow, T.C.

    1983-05-01

    The high affinity binding sites for the antidepressant desmethlyimipramine (DMI) have been localized in rat brain by quantitative autoradiography. There are high concentrations of binding sites in the locus ceruleus, the anterior ventral thalamus, the ventral portion of the bed nucleus of the stria terminalis, the paraventricular and the dorsomedial nuclei of the hypothalamus. The distribution of DMI binding sites is in striking accord with the distribution of norepinephrine terminals. Pretreatment of rats with the neurotoxin 6-hydroxydopamine, which causes a selective degeneration of catecholamine terminals, results in 60 to 90% decrease in DMI binding. These data support the idea that high affinity binding sites for DMI are located on presynaptic noradrenergic terminals.

  10. Glutamate and the aggression neural circuit in adolescent anabolic steroid-treated Syrian hamsters (Mesocricetus auratus).

    PubMed

    Carrillo, Maria; Ricci, Lesley A; Melloni, Richard H

    2011-10-01

    Adolescent exposure to anabolic androgenic steroids (AAS) alters the development and activity of the glutamate neural system in the latero-anterior hypothalamus (LAH) in hamsters (Mesocricetus auratus); that is, an important neural component of the adolescent AAS-induced aggressive response. In this article, we used retrograde tracing to investigate glutamate-specific alterations in the connections between the LAH and several other nuclei implicated in adolescent AAS-induced aggression. Briefly, hamsters were treated with AAS or sesame-oil control during adolescence and then microinjected with retrograde tracer into the medial amygdala (MeA), lateral septum (LS), or bed nucleus of the stria terminalis (BNST). Brains were then processed for vesicular glutamate transporter 2 (VGLUT2) and examined for AAS-induced changes in the number VGLUT2 cells containing retrograde tracer (VGLUT2/tracer) within the LAH. It is interesting to note that while aggressive AAS-treated hamsters injected retrograde tracer into the MeA showed a significant reduction in the number of VGLUT2/tracer cells in the LAH, aggressive AAS-treated hamsters injected tracer into the BNST showed a significant increase in the number of VGLUT2/tracer cells in the LAH when compared with controls. Last, AAS hamsters injected with tracer into the LS had a comparable number of LAH-VGLUT2/tracer cells to controls. The current results indicate that glutamate likely functions as the major aggression output system from the LAH and that adolescent AAS treatment significantly alters the neural circuitry modulating aggression. Moreover, increases in the number of glutamate projections from the LAH to the BNST in AAS hamsters identify the BNST as an area particularly important for the regulation of AAS-induced aggression.

  11. Estradiol selectively reduces central neural activation induced by hypertonic NaCl infusion in ovariectomized rats.

    PubMed

    Jones, Alexis B; Bass, Eryn E; Fan, Liming; Curtis, Kathleen S

    2012-09-10

    We recently reported that the latency to begin drinking water during slow, intravenous infusion of a concentrated NaCl solution was shorter in estradiol-treated ovariectomized rats compared to oil vehicle-treated rats, despite comparably elevated plasma osmolality. To test the hypothesis that the decreased latency to begin drinking is attributable to enhanced detection of increased plasma osmolality by osmoreceptors located in the CNS, the present study used immunocytochemical methods to label fos, a marker of neural activation. Increased plasma osmolality did not activate the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), or the nucleus of the solitary tract (NTS) in either oil vehicle-treated rats or estradiol-treated rats. In contrast, hyperosmolality increased fos labeling in the area postrema (AP), the paraventricular nucleus of the hypothalamus (PVN) and the rostral ventrolateral medulla (RVLM) in both groups; however, the increase was blunted in estradiol-treated rats. These results suggest that estradiol has selective effects on the sensitivity of a population of osmo-/Na(+)-receptors located in the AP, which, in turn, alters activity in other central areas associated with responses to increased osmolality. In conjunction with previous reports that hyperosmolality increases blood pressure and that elevated blood pressure inhibits drinking, the current findings of reduced activation in AP, PVN, and RVLM-areas involved in sympathetic nerve activity-raise the possibility that estradiol blunts HS-induced blood pressure changes. Thus, estradiol may eliminate or reduce the initial inhibition of water intake that occurs during increased osmolality, and facilitate a more rapid behavioral response, as we observed in our recent study.

  12. Regulatory interactions of stress and reward on rat forebrain opioidergic and GABAergic circuitry.

    PubMed

    Christiansen, A M; Herman, J P; Ulrich-Lai, Y M

    2011-03-01

    Palatable food intake reduces stress responses, suggesting that individuals may consume such ?comfort? food as self-medication for stress relief. The mechanism by which palatable foods provide stress relief is not known, but likely lies at the intersection of forebrain reward and stress regulatory circuits. Forebrain opioidergic and gamma-aminobutyric acid ergic signaling is critical for both reward and stress regulation, suggesting that these systems are prime candidates for mediating stress relief by palatable foods. Thus, the present study (1) determines how palatable ?comfort? food alters stress-induced changes in the mRNA expression of inhibitory neurotransmitters in reward and stress neurocircuitry and (2) identifies candidate brain regions that may underlie comfort food-mediated stress reduction. We used a model of palatable ?snacking? in combination with a model of chronic variable stress followed by in situ hybridization to determine forebrain levels of pro-opioid and glutamic acid decarboxylase (GAD) mRNA. The data identify regions within the extended amygdala, striatum, and hypothalamus as potential regions for mediating hypothalamic-pituitary-adrenal axis buffering following palatable snacking. Specifically, palatable snacking alone decreased pro-enkephalin-A (ENK) mRNA expression in the anterior bed nucleus of the stria terminalis (BST) and the nucleus accumbens, and decreased GAD65 mRNA in the posterior BST. Chronic stress alone increased ENK mRNA in the hypothalamus, nucleus accumbens, amygdala, and hippocampus; increased dynorphin mRNA in the nucleus accumbens; increased GAD65 mRNA in the anterior hypothalamus and BST; and decreased GAD65 mRNA in the dorsal hypothalamus. Importantly, palatable food intake prevented stress-induced gene expression changes in subregions of the hypothalamus, BST, and nucleus accumbens. Overall, these data suggest that complex interactions exist between brain reward and stress pathways and that palatable snacking can

  13. Inhibition of the central extended amygdala by loud noise and restraint stress

    PubMed Central

    Day, Heidi E. W.; Nebel, Scott; Sasse, Sarah; Campeau, Serge

    2008-01-01

    It is well established that the central nucleus of the amygdala (CEA) is involved in responses to stress, fear and anxiety. Many studies have used c-fos expression to map the brain's response to processive stress, but curiously the CEA generally is not highly activated. We have previously shown that exposure to a novel vs. home environment reduces amphetamine-induced activation of the lateral CEA (CEAl) and the oval nucleus of the bed nucleus of the stria terminalis (BSTov). This is consistent with the idea that processive stress inhibits neurons in these nuclei. We have tested this hypothesis by exposing rats to noise, at a range of intensities from non-stressful to stressful, or to restraint conditions, immediately after a remote injection of amphetamine, 2 mg/kg i.p., or interleukin-1β (IL-1β) 0.5 μg/kg i.p. (used to obtain a level of c-fos mRNA against which to measure inhibition). In keeping with our hypothesis, amphetamine- or IL-1β-induced c-fos and zif-268 mRNA were significantly decreased in the CEAl and BSTov under conditions of loud noise or restraint stress compared with control conditions. This inhibition does not require a stress-induced rise in corticosterone because data were similar in animals that had been adrenalectomized with a low-dose corticosterone replacement. As both the CEAl and BSTov are highly γ-aminobutyric acid (GABA) -ergic and project to the medial CEA (CEAm), their inhibition potentially causes an increased input to the CEAm. As the CEAm is a major output nucleus of the amygdala, this could have important consequences within the neural circuitry controlling responses to processive stress. PMID:15673443

  14. Hypothalamic vasopressin systems are more sensitive to the long term effects of social defeat in males versus females

    PubMed Central

    Steinman, M.Q.; Laredo, S.A.; Lopez, E.M.; Manning, C.E.; Hao, R.C.; Doig, I.E.; Campi, K.L.; Flowers, A.E.; Knight, J.K.; Trainor, B.C.

    2014-01-01

    Vasopressin signaling has important effects on the regulation of social behaviors and stress responses, and is considered a promising pathway to target for new therapeutics of stress-induced psychiatric disorders. Although there is evidence for sex differences in the behavioral effects of arginine vasopressin (AVP), few data have directly compared the effects of stress on endogenous AVP signaling in males and females. We used California mice (Peromyscus californicus) to study the short and long term effects of social defeat stress on AVP immunoreactive cells in the paraventricular nucleus (PVN) and the posteromedial bed nucleus of the stria terminalis (BNSTmp). Acute exposure to defeat increased AVP/c-fos cells in the PVN and SON of both males and females. In contrast, there were sex differences in the long term effects of defeat. Males but not females exposed to defeat had less avp mRNA in the PVN, and in two experiments defeat reduced the number of AVP positive cells in the caudal PVN of males but not females. Interestingly, during relatively benign social encounters with a target mouse, there was a rapid decrease in AVP percent staining (including cell bodies and fibers) in the PVN of males but not females. Defeat reduced AVP percent staining in males, but did not block the socially induced decrease in percent staining. When mice were tested in resident-intruder tests, males exposed to defeat males were no less aggressive than control males whereas aggression was abolished in females. However, bouts of aggression were positively correlated with the number of AVP neurons in the BNSTmp of control males but not stressed males, suggesting that different mechanisms mediate aggression in control and stressed males. These data show that while acute AVP responses to defeat are similar in males and females, the long term effects of defeat on AVP are stronger in males. PMID:25306217

  15. Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide.

    PubMed

    Konsman, J P; Veeneman, J; Combe, C; Poole, S; Luheshi, G N; Dantzer, R

    2008-12-01

    Although receptors for the pro-inflammatory cytokine interleukin-1 have long been known to be expressed in the brain, their role in fever and behavioural depression observed during the acute phase response (APR) to tissue infection remains unclear. This may in part be due to the fact that interleukin-1 in the brain is bioactive only several hours after peripheral administration of bacterial lipopolysaccharide (LPS). To study the role of cerebral interleukin-1 action in temperature and behavioural changes, and activation of brain structures during the APR, interleukin-1 receptor antagonist (IL-1ra; 100 microg) was infused into the lateral brain ventricle 4 h after intraperitoneal (i.p.) LPS injection (250 microg/kg) in rats. I.p. LPS administration induced interleukin-1beta (IL-1beta) production in systemic circulation as well as in brain circumventricular organs and the choroid plexus. Intracerebroventricular (i.c.v.) infusion of IL-1ra 4 h after i.p. LPS injection attenuated the reduction in social interaction, a cardinal sign of behavioural depression during sickness, and c-Fos expression in the amygdala and bed nucleus of the stria terminalis. However, LPS-induced fever, rises in plasma corticosterone, body weight loss and c-Fos expression in the hypothalamus and caudal brainstem were not altered by i.c.v. infusion of IL-1ra. These findings, together with our previous observations showing that i.c.v. infused IL-1ra diffuses throughout perivascular spaces, where macrophages express interleukin-1 receptors, can be interpreted to suggest that circulating or locally produced brain IL-1beta acts on these cells to bring about behavioural depression and activation of limbic structures during the APR after peripheral LPS administration.

  16. Changes in central sodium and not osmolarity or lactate induce panic-like responses in a model of panic disorder.

    PubMed

    Molosh, Andre I; Johnson, Philip L; Fitz, Stephanie D; Dimicco, Joseph A; Herman, James P; Shekhar, Anantha

    2010-05-01

    Panic disorder is a severe anxiety disorder characterized by recurrent panic attacks that can be consistently provoked with intravenous (i.v.) infusions of hypertonic (0.5 M) sodium lactate (NaLac), yet the mechanism/CNS site by which this stimulus triggers panic attacks is unclear. Chronic inhibition of GABAergic synthesis in the dorsomedial hypothalamus/perifornical region (DMH/PeF) of rats induces a vulnerability to panic-like responses after i.v. infusion of 0.5 M NaLac, providing an animal model of panic disorder. Using this panic model, we previously showed that inhibiting the anterior third ventricle region (A3Vr; containing the organum vasculosum lamina terminalis, the median preoptic nucleus, and anteroventral periventricular nucleus) attenuates cardiorespiratory and behavioral responses elicited by i.v. infusions of NaLac. In this study, we show that i.v. infusions of 0.5 M NaLac or sodium chloride, but not iso-osmolar D-mannitol, increased 'anxiety' (decreased social interaction) behaviors, heart rate, and blood pressure responses. Using whole-cell patch-clamp preparations, we also show that bath applications of NaLac (positive control), but not lactic acid (lactate stimulus) or D-mannitol (osmolar stimulus), increases the firing rates of neurons in the A3Vr, which are retrogradely labeled from the DMH/PeF and which are most likely glutamatergic based on a separate study using retrograde tracing from the DMH/PeF in combination with in situ hybridization for vesicular glutamate transporter 2. These data show that hypertonic sodium, but not hyper-osmolarity or changes in lactate, is the key stimulus that provokes panic attacks in panic disorder, and is consistent with human studies.

  17. Distribution of sup 125 I-neurotensin binding sites in human forebrain: Comparison with the localization of acetylcholinesterase

    SciTech Connect

    Szigethy, E.; Quirion, R.; Beaudet, A. )

    1990-07-22

    The distribution of 125I-neurotensin binding sites was compared with that of acetylcholinesterase reactivity in the human basal forebrain by using combined light microscopic radioautography/histochemistry. High 125I-neurotensin binding densities were observed in the bed nucleus of the stria terminalis, islands of Calleja, claustrum, olfactory tubercle, and central nucleus of the amygdala; lower levels were seen in the caudate, putamen, medial septum, diagonal band nucleus, and nucleus basalis of Meynert. Adjacent sections processed for cholinesterase histochemistry demonstrated a regional overlap between the distribution of labeled neurotensin binding sites and that of intense acetylcholinesterase staining in all of the above regions, except in the bed nucleus of the stria terminalis, claustrum, and central amygdaloid nucleus, where dense 125I-neurotensin labeling was detected over areas containing only weak to moderate cholinesterase staining. At higher magnification, 125I-neurotensin-labeled binding sites in the islands of Calleja, supraoptic nucleus of the hypothalamus, medial septum, diagonal band nucleus, and nucleus basalis of Meynert were selectively associated with neuronal perikarya found to be cholinesterase-positive in adjacent sections. Moderate 125I-neurotensin binding was also apparent over the cholinesterase-reactive neuropil of these latter three regions. These data suggest that neurotensin (NT) may directly influence the activity of magnocellular cholinergic neurons in the human basal forebrain, and may be involved in the physiopathology of dementing disorders such as Alzheimer's disease, in which these neurons have been shown to be affected.

  18. Connections of the corticomedial amygdala in the golden hamster. II. Efferents of the ''olfactory amygdala''

    SciTech Connect

    Kevetter, G.A.; Winans, S.S.

    1981-03-20

    The anterior cortical (C1) and posterolateral cortical (C2) nuclei of the amygdala are designated the ''olfactory amygdala'' because they each receive direct projections from the main olfactory bulb. The efferents of these nuclei were traced after stereotaxic placement of 1-5 muCi tritiated proline in the corticomedial amygdala of the male golden hamsters. Following survival times of 12, 24, or 48 hours, 20 micron frozen sections of the brains were processed for light microscopic autoradiography. Efferents from C2 terminate in layers II and III of the olfactory tubercle and in layer Ib of pars ventralis and pars medialis of the anterior olfactory nucleus. Fibers from this nucleus also project to layers I and II of the infralimbic cortex and to the molecular layer of the agranular insular cortex. More posteriorly, fibers from C2 terminate in layer I of the dorsolateral entorhinal cortex, and in the endopiriform nucleus. From C1, efferent fibers travel in the stria terminalis and terminate in the precommissural bed nucleus of the stria terminalis and in the mediobasal hypothalamus. Efferents from C1 also innervate the molecular layer of C2, the amygdalo-hippocampal area, and the adjacent piriform cortex. Neurons in both C1 and C2 project to the molecular layer of the medial amygdaloid nucleus and the posteromedial cortical nucleus of the amygdala, the plexiform layer of the ventral subiculum, and the molecular layer of the lateral entorhinal cortex.

  19. Distribution of vasopressin, oxytocin and vasoactive intestinal polypeptide in the hypothalamus and extrahypothalamic regions of tree shrews.

    PubMed

    Ni, R-J; Shu, Y-M; Wang, J; Yin, J-C; Xu, L; Zhou, J-N

    2014-04-18

    Vasopressin (VP), oxytocin (OXT) and vasoactive intestinal polypeptide (VIP) in the brain modulate physiological and behavioral processes in many vertebrates. Day-active tree shrews, the closest relatives of primates, live singly or in pairs in territories that they defend vigorously against intruding conspecifics. However, anatomy concerning peptidergic neuron distribution in the tree shrew brain is less clear. Here, we examined the distribution of VP, OXT and VIP immunoreactivity in the hypothalamus and extrahypothalamic regions of tree shrews (Tupaia belangeri chinensis) using the immunohistochemical techniques. Most of VP and OXT immunoreactive (-ir) neurons were found in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. In addition, VP-ir or OXT-ir neurons were scattered in the preoptic area, anterior hypothalamic areas, dorsomedial hypothalamic nucleus, stria terminalis, bed nucleus of the stria terminalis and medial amygdala. Interestingly, a high density of VP-ir fibers within the ventral lateral septum was observed in males but not in females. Both VP-ir and VIP-ir neurons were found in different subdivisions of the suprachiasmatic nucleus (SCN) with partial overlap. VIP-ir cells and fibers were also scattered in the cerebral cortex, anterior olfactory nucleus, amygdala and dentate gyrus of the hippocampus. These findings provide a comprehensive description of VIP and a detailed mapping of VP and OXT in the hypothalamus and extrahypothalamic regions of tree shrews, which is an anatomical basis for the participation of these neuropeptides in the regulation of circadian behavior and social behavior.

  20. Distribution of the inositol 1,4,5-trisphosphate receptor, P400, in adult rat brain.

    PubMed

    Rodrigo, J; Suburo, A M; Bentura, M L; Fernández, T; Nakade, S; Mikoshiba, K; Martínez-Murillo, R; Polak, J M

    1993-11-15

    The distribution of the inositol 1,4,5-trisphosphate receptor protein, P400, was investigated in adult rat brain by immunocytochemistry with the monoclonal antibody 4C11 raised against mouse cerebellar inositol 1,4,5-trisphosphate receptor protein. Immunoreactive neuronal cell bodies were detected in the cerebral cortex, the claustrum, the endopiriform nucleus, the corpus callosum, the anterior olfactory nuclei, the olfactory tubercle, the nucleus accumbens, the lateral septum, the bed nucleus of the stria terminalis, the hippocampal formation, the dentate gyrus, the caudate-putamen, the fundus striatum, the amygdaloid complex, the thalamus, the caudolateral part of the hypothalamus, the supramammillary nuclei, the substantia nigra, the pedunculopontine tegmental nucleus, the ventrotegmental area, the Purkinje cells in the cerebellum, the dorsal cochlear nucleus, the subnucleus oralis and caudalis of trigeminal nerve, and the dorsal horn of the spinal cord. Immunoreactive fibres were found in the medial forebrain bundle, the globus pallidus, the stria terminalis, the pyramidal tract, the spinal tract of trigeminal nerve, and the ventral horn of spinal cord. Nerve fibres forming a dense plexus ending in terminal-like boutons were detected in relation to nonimmunoreactive neurons of the dentate, interpositus, and fastigial nuclei of the cerebellum and around neurons of the vestibular nuclei. This receptor protein binds a specific second messenger, inositol 1,4,5-trisphosphate, which produces a mobilization of intracellular Ca2+ and a modulation of transmitter release.

  1. Segregated pathways to the vomeronasal amygdala: differential projections from the anterior and posterior divisions of the accessory olfactory bulb.

    PubMed

    Mohedano-Moriano, Alicia; Pro-Sistiaga, Palma; Ubeda-Bañón, Isabel; Crespo, Carlos; Insausti, Ricardo; Martinez-Marcos, Alino

    2007-04-01

    Apically and basally located receptor neurons in the vomeronasal sensory epithelium express G(i2 alpha)- and G(o alpha)-proteins, V1R and V2R vomeronasal receptors, project to the anterior and posterior accessory olfactory bulb and respond to different stimuli, respectively. The extent to which secondary projections from the two portions of the accessory olfactory bulb are convergent in the vomeronasal amygdala is controversial. This issue is addressed by using anterograde and retrograde tract-tracing methods in rats including electron microscopy. Injections of dextran-amines, Fluoro Gold, cholera toxin-B subunit and Fast Blue were delivered to the anterior and posterior accessory olfactory bulb, bed nucleus of the stria terminalis, dorsal anterior amygdala and bed nucleus of the accessory olfactory tract/anteroventral medial amygdaloid nucleus. We have demonstrated that, apart from common vomeronasal-recipient areas, only the anterior accessory olfactory bulb projects to the bed nucleus of the stria terminalis, medial division, posteromedial part, and only the posterior accessory olfactory bulb projects to the dorsal anterior amygdala and deep cell layers of the bed nucleus of the accessory olfactory tract and the anteroventral medial amygdaloid nucleus. These results provide evidence that, excluding areas of convergence, the V1R and V2R vomeronasal pathways project to specific areas of the amygdala. These two vomeronasal subsystems are therefore anatomically and functionally separated in the telencephalon.

  2. Lipopolysaccharide-Induced Middle Ear Inflammation Disrupts the cochlear Intra-Strial Fluid–Blood Barrier through Down-Regulation of Tight Junction Proteins

    PubMed Central

    Zhang, Jinhui; Chen, Songlin; Hou, Zhiqiang; Cai, Jing; Dong, Mingmin; Shi, Xiaorui

    2015-01-01

    Middle ear infection (or inflammation) is the most common pathological condition that causes fluid to accumulate in the middle ear, disrupting cochlear homeostasis. Lipopolysaccharide, a product of bacteriolysis, activates macrophages and causes release of inflammatory cytokines. Many studies have shown that lipopolysaccharides cause functional and structural changes in the inner ear similar to that of inflammation. However, it is specifically not known how lipopolysaccharides affect the blood-labyrinth barrier in the stria vascularis (intra-strial fluid–blood barrier), nor what the underlying mechanisms are. In this study, we used a cell culture-based in vitro model and animal-based in vivo model, combined with immunohistochemistry and a vascular leakage assay, to investigate lipopolysaccharide effects on the integrity of the mouse intra-strial fluid–blood barrier. Our results show lipopolysaccharide-induced local infection significantly affects intra-strial fluid–blood barrier component cells. Pericytes and perivascular-resident macrophage-like melanocytes are particularly affected, and the morphological and functional changes in these cells are accompanied by substantial changes in barrier integrity. Significant vascular leakage is found in the lipopolysaccharide treated-animals. Consistent with the findings from the in vivo animal model, the permeability of the endothelial cell monolayer to FITC-albumin was significantly higher in the lipopolysaccharide-treated monolayer than in an untreated endothelial cell monolayer. Further study has shown the lipopolysaccharide-induced inflammation to have a major effect on the expression of tight junctions in the blood barrier. Lipopolysaccharide was also shown to cause high frequency hearing loss, corroborated by previous reports from other laboratories. Our findings show lipopolysaccharide-evoked middle ear infection disrupts inner ear fluid balance, and its particular effects on the intra-strial fluid

  3. Lipopolysaccharide-induced middle ear inflammation disrupts the cochlear intra-strial fluid-blood barrier through down-regulation of tight junction proteins.

    PubMed

    Zhang, Jinhui; Chen, Songlin; Hou, Zhiqiang; Cai, Jing; Dong, Mingmin; Shi, Xiaorui

    2015-01-01

    Middle ear infection (or inflammation) is the most common pathological condition that causes fluid to accumulate in the middle ear, disrupting cochlear homeostasis. Lipopolysaccharide, a product of bacteriolysis, activates macrophages and causes release of inflammatory cytokines. Many studies have shown that lipopolysaccharides cause functional and structural changes in the inner ear similar to that of inflammation. However, it is specifically not known how lipopolysaccharides affect the blood-labyrinth barrier in the stria vascularis (intra-strial fluid-blood barrier), nor what the underlying mechanisms are. In this study, we used a cell culture-based in vitro model and animal-based in vivo model, combined with immunohistochemistry and a vascular leakage assay, to investigate lipopolysaccharide effects on the integrity of the mouse intra-strial fluid-blood barrier. Our results show lipopolysaccharide-induced local infection significantly affects intra-strial fluid-blood barrier component cells. Pericytes and perivascular-resident macrophage-like melanocytes are particularly affected, and the morphological and functional changes in these cells are accompanied by substantial changes in barrier integrity. Significant vascular leakage is found in the lipopolysaccharide treated-animals. Consistent with the findings from the in vivo animal model, the permeability of the endothelial cell monolayer to FITC-albumin was significantly higher in the lipopolysaccharide-treated monolayer than in an untreated endothelial cell monolayer. Further study has shown the lipopolysaccharide-induced inflammation to have a major effect on the expression of tight junctions in the blood barrier. Lipopolysaccharide was also shown to cause high frequency hearing loss, corroborated by previous reports from other laboratories. Our findings show lipopolysaccharide-evoked middle ear infection disrupts inner ear fluid balance, and its particular effects on the intra-strial fluid-blood barrier

  4. Dynamic changes in oxytocin receptor expression and activation at parturition in the rat brain.

    PubMed

    Meddle, Simone L; Bishop, Valerie R; Gkoumassi, Effimia; van Leeuwen, Fred W; Douglas, Alison J

    2007-10-01

    Oxytocin plays a pivotal role in rat parturition, acting within the brain to facilitate its own release in the supraoptic nucleus (SON) and paraventricular nucleus, and to stimulate maternal behavior. We investigated oxytocin receptor (OTR) expression and activation perinatally. Using a (35)S-labeled riboprobe complementary to OTR mRNA, OTR expression was quantified in proestrus virgin, 21- and 22-day pregnant, parturient (90 min. from pup 1 birth), and postpartum (4-12 h from parturition) rats. Peak OTR mRNA expression was observed at parturition in the SON, brainstem regions, medial preoptic area (mPOA), bed nucleus of the stria terminalis (BnST), and olfactory bulbs, but there was no change in the paraventricular nucleus and lateral septum. OTR mRNA expression was increased on the day of expected parturition in the SON and brainstem, suggesting that oxytocin controls the pathway mediating input from uterine signals. Likewise, OTR mRNA expression was increased in the mPOA and BnST during labor/birth. In the olfactory bulbs and medial amygdala, parturition induced increased OTR mRNA expression compared with pre-parturition, reflecting their immediate response to new stimuli at birth. Postpartum OTR expression in all brain regions returned to levels observed in virgin rats. Parturition significantly increased the number of double-immunolabeled cells for Fos and OTR within the SON, brainstem, BnST, and mPOA regions compared with virgin rats. Thus, there are dynamic region-dependent changes in OTR-expressing cells at parturition. This altered OTR distribution pattern in the brain perinatally reflects the crucial role oxytocin plays in orchestrating both birth and maternal behavior.

  5. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation

    PubMed Central

    Rodgers, Ali B.; Morgan, Christopher P.; Bronson, Stefanie L.; Revello, Sonia; Bale, Tracy L.

    2013-01-01

    Neuropsychiatric disease frequently presents with an underlying hypo- or hyper- reactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric disease risk, and likely contribute to stress dysregulation. While maternal influences have been extensively examined, much less is known regarding the specific role of paternal factors. To investigate the potential mechanisms by which paternal stress may contribute to offspring hypothalamic-pituitary-adrenal (HPA) axis dysregulation, we exposed mice to six weeks of chronic stress prior to breeding. As epidemiological studies support variation in paternal germ cell susceptibility to reprogramming across the lifespan, male stress exposure occurred either throughout puberty or in adulthood. Remarkably, offspring of sires from both paternal stress groups displayed significantly reduced HPA axis stress responsivity. Gene set enrichment analyses in offspring stress regulating brain regions, the paraventricular nucleus (PVN) and the bed nucleus of stria terminalis (BNST), revealed global pattern changes in transcription suggestive of epigenetic reprogramming and consistent with altered offspring stress responsivity, including increased expression of glucocorticoid-responsive genes in the PVN. In examining potential epigenetic mechanisms of germ cell transmission, we found robust changes in sperm miRNA (miR) content, where nine specific miRs were significantly increased in both paternal stress groups. Overall, these results demonstrate that paternal experience across the lifespan can induce germ cell epigenetic reprogramming and impact offspring HPA stress axis regulation, and may therefore offer novel insight into factors influencing neuropsychiatric disease risk. PMID:23699511

  6. Forebrain patterns of c-Fos and FosB induction during cancer-associated anorexia-cachexia in rat.

    PubMed

    Konsman, Jan Pieter; Blomqvist, Anders

    2005-05-01

    Forebrain structures are necessary for the initiation of food intake and its coupling to energy expenditure. The cancer-related anorexia-cachexia syndrome is typified by a prolonged increase in metabolic rate resulting in body weight loss which, paradoxically, is accompanied by reduced food intake. The aim of the present work was to study the forebrain expression of Fos proteins as activation markers and thus to identify potential neurobiological mechanisms favouring catabolic processes or modulating food intake in rats suffering from cancer-related anorexia-cachexia. Neurons in forebrain structures showing most pronounced induction of Fos proteins were further identified neurochemically. To provoke anorexia-cachexia, cultured Morris hepatoma 7777 cells were injected subcutaneously in Buffalo rats. This resulted in a slowly growing tumour inducing approximately 7% body weight loss and a 20% reduction in food intake when the tumour represented 1-2% of body mass. Anorexia-cachexia in these animals was found to be accompanied by Fos induction in several hypothalamic nuclei including the paraventricular and ventromedial hypothalamus, in the parastrial nucleus, the amygdala, the bed nucleus of the stria terminalis, ventral striatal structures and the piriform and somatosensory cortices. Neurochemical identification revealed that the vast majority of FosB-positive neurons in the nucleus accumbens, ventral caudate-putamen and other ventral striatal structures contained prodynorphin or proenkephalin mRNA. These findings indicate that forebrain structures that are part of neuronal networks modulating catabolic pathways and food ingestion are activated during tumour-associated anorexia-cachexia and may contribute to the lack of compensatory eating in response to weight loss characterizing this syndrome.

  7. Region-dependent dynamics of cAMP response element-binding protein phosphorylation in the basal ganglia

    PubMed Central

    Liu, Fu-Chin; Graybiel, Ann M.

    1998-01-01

    The cAMP response element-binding protein (CREB) is an activity-dependent transcription factor that is involved in neural plasticity. The kinetics of CREB phosphorylation have been suggested to be important for gene activation, with sustained phosphorylation being associated with downstream gene expression. If so, the duration of CREB phosphorylation might serve as an indicator for time-sensitive plastic changes in neurons. To screen for regions potentially involved in dopamine-mediated plasticity in the basal ganglia, we used organotypic slice cultures to study the patterns of dopamine- and calcium-mediated CREB phosphorylation in the major subdivisions of the striatum. Different durations of CREB phosphorylation were evoked in the dorsal and ventral striatum by activation of dopamine D1-class receptors. The same D1 stimulus elicited (i) transient phosphorylation (≤15 min) in the matrix of the dorsal striatum; (ii) sustained phosphorylation (≤2 hr) in limbic-related structures including striosomes, the nucleus accumbens, the fundus striati, and the bed nucleus of the stria terminalis; and (iii) prolonged phosphorylation (up to 4 hr or more) in cellular islands in the olfactory tubercle. Elevation of Ca2+ influx by stimulation of L-type Ca2+ channels, NMDA, or KCl induced strong CREB phosphorylation in the dorsal striatum but not in the olfactory tubercle. These findings differentiate the response of CREB to dopamine and calcium signals in different striatal regions and suggest that dopamine-mediated CREB phosphorylation is persistent in limbic-related regions of the neonatal basal ganglia. The downstream effects activated by persistent CREB phosphorylation may include time-sensitive neuroplasticity modulated by dopamine. PMID:9539803

  8. Nucleus Paragigantocellularis Afferents in Male and Female Rats: Organization, Gonadal Steroid Sensitivity, and Activation During Sexual Behavior

    PubMed Central

    Normandin, Joseph J.; Murphy, Anne Z.

    2010-01-01

    The central regulation of genital reflexes is poorly understood. The brainstem nucleus paragigantocellularis (nPGi) of rats is a well-established source of tonic inhibition of genital reflexes. However the organization, gonadal steroid sensitivity, and activity of nPGi afferents during sex have not been fully characterized in male and female rats. To delineate the anatomical and physiological organization of nPGi afferents, the retrograde tracer Fluorogold (FG) was injected into the nPGi of sexually experienced male and female rats. Animals engaged in sexual behavior one hour before sacrifice. Cells containing FG, estrogen receptor alpha (ERα), androgen receptor (AR), and the immediate-early gene product Fos were identified immunocytochemically. Retrograde labeling from the nPGi was prominent in the bed nucleus of the stria terminalis, paraventricular nucleus, posterior hypothalamus, precommissural nucleus, deep mesencephalic nucleus, and periaqueductal gray (PAG) of both sexes. Sex differences were observed in the caudal medial preoptic area (MPO), with significantly more FG+ cells observed in males and in the PAG and inferior colliculus where significantly more FG+ cells were observed in females. The majority of regions that contained FG+ cells also contained ERα or AR, indicating sensitivity to gonadal steroids. The proportions of FG+ cells that co-localized with sex-induced Fos was high in the PVN of both sexes, high in the MPO of males, but low in the PAG of both sexes despite the large number of PAG-nPGi output neurons and Fos+ cells in both sexes. The characterization of these afferents will lead to a further understanding of the neural regulation of genital reflexes. PMID:18393295

  9. Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

    PubMed

    Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

    2017-03-22

    The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.Neuropsychopharmacology advance online

  10. Somatostatin receptor subtype 4 activation is involved in anxiety and depression-like behavior in mouse models.

    PubMed

    Scheich, Bálint; Gaszner, Balázs; Kormos, Viktória; László, Kristóf; Ádori, Csaba; Borbély, Éva; Hajna, Zsófia; Tékus, Valéria; Bölcskei, Kata; Ábrahám, István; Pintér, Erika; Szolcsányi, János; Helyes, Zsuzsanna

    2016-02-01

    Somatostatin regulates stress-related behavior and its expression is altered in mood disorders. However, little is known about the underlying mechanisms, especially about the importance of its receptors (sst1-sst5) in anxiety and depression-like behavior. Here we analyzed the potential role of sst4 receptor in these processes, since sst4 is present in stress-related brain regions, but there are no data about its functional relevance. Genetic deletion of sst4 (Sstr4(-/-)) and its pharmacological activation with the newly developed selective non-peptide agonist J-2156 were used. Anxiety was examined in the elevated plus maze (EPM) and depression-like behavior in the forced swim (FST) and tail suspension tests (TST). Neuronal activation during the TST was monitored by Fos immunohistochemistry, receptor expression was identified by sst4(LacZ) immunostaining in several brain regions. Sstr4(-/-) mice showed increased anxiety in the EPM and enhanced depression-like behavior in the FST. J-2156 (100 μg/kg i.p.) exhibited anxiolytic effect in the EPM and decreased immobility in the TST. J-2156 alone did not influence Fos immunoreactivity in intact mice, but significantly increased the stress-induced Fos response in the dorsal raphe nucleus, central projecting Edinger-Westphal nucleus, periaqueductal gray matter, the magnocellular, but not the parvocellular part of the hypothalamic paraventricular nucleus, lateral septum, bed nucleus of the stria terminalis and the amygdala. Notably, sst4(LacZ) immunoreactivity occurred in the central and basolateral amygdala. Together, these studies reveal that sst4 mediates anxiolytic and antidepressant-like effects by enhancing the stress-responsiveness of several brain regions with special emphasis on the amygdala.

  11. Olfactory systems and neural circuits that modulate predator odor fear

    PubMed Central

    Takahashi, Lorey K.

    2014-01-01

    When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator

  12. Nicotine evoked improvement in learning and memory is mediated through NPY Y1 receptors in rat model of Alzheimer's disease.

    PubMed

    Rangani, Ritesh J; Upadhya, Manoj A; Nakhate, Kartik T; Kokare, Dadasaheb M; Subhedar, Nishikant K

    2012-02-01

    We investigated the role of endogenous neuropeptide Y (NPY) system in nicotine-mediated improvement of learning and memory in rat model of Alzheimer's disease (AD). Intracerebroventricular (icv) colchicine treatment induced AD-like condition in rats and showed increased escape latency (decreased learning), and amnesic condition in probe test in Morris water maze. In these rats, nicotine (0.5mg/kg, intraperitoneal), NPY (100 ng/rat, icv) or NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY (0.04 ng/rat, icv) decreased escape latency by 54.76%, 55.81% and 44.18%, respectively, on day 4 of the acquisition. On the other hand, selective NPY Y1 receptor antagonist, BIBP3226 (icv) produced opposite effect (44.18%). In the probe test conducted at 24h time point, nicotine, NPY or [Leu(31), Pro(34)]-NPY increased the time spent by 72.72%, 44.11% and 26.47%, respectively; while BIBP3226 caused reduction (8.82%). It seems that while NPY or [Leu(31), Pro(34)]-NPY potentiated, BIBP3226 attenuated the learning and memory enhancing effects of nicotine. Brains of colchicine treated rats showed significant reduction in NPY-immunoreactivity in the nucleus accumbens shell (cells 62.23% and fibers 50%), bed nucleus of stria terminalis (fibers 71.58%), central nucleus of amygdala (cells 74.33%), arcuate nucleus (cells 70.97% and fibers 69.65%) and dentate gyrus (cells 58.54%). However, in these rats nicotine treatment for 4 days restored NPY-immunoreactivity to the control level. We suggest that NPY, perhaps acting via NPY Y1 receptors, might interact with the endogenous cholinergic system and play a role in improving the learning and memory processes in the rats with AD-like condition.

  13. From here to paternity: neural correlates of the onset of paternal behavior in California mice (Peromyscus californicus).

    PubMed

    de Jong, Trynke R; Chauke, Miyetani; Harris, Breanna N; Saltzman, Wendy

    2009-08-01

    In a minority of mammalian species, including humans, fathers play a significant role in infant care. Compared to maternal behavior, the neural and hormonal bases of paternal care are poorly understood. We analyzed behavioral, neuronal and neuropeptide responses towards unfamiliar pups in biparental California mice, comparing males housed with another male ("virgin males") or with a female before ("paired males") or after ("new fathers") the birth of their first litter. New fathers approached pups more rapidly and spent more time engaging in paternal behavior than virgin males. In each cage housing two virgin males, one was spontaneously paternal and one was not. New fathers and paired males spent more time sniffing and touching a wire mesh ball containing a newborn pup than virgin males. Only new fathers showed significantly increased Fos-like immunoreactivity in the medial preoptic nucleus (MPO) following exposure to a pup-containing ball, as compared to an empty ball. Moreover, Fos-LIR in the bed nucleus of the stria terminalis (STMV and STMPM) and caudal dorsal raphe nucleus (DRC) was increased in new fathers, independent of test condition. No differences were found among the groups in Fos-LIR in oxytocinergic or vasopressinergic neurons. These results suggest that sexual and paternal experiences facilitate paternal behavior, but other cues play a role as well. Paternal experience increases Fos-LIR induced by distal pup cues in the MPO, but not in oxytocin and vasopressin neurons. Fatherhood also appears to alter neurotransmission in the BNST and DRC, regions implicated in emotionality and stress-responsiveness.

  14. Immediate and lasting effects of chronic daily methamphetamine exposure on activation of cells in hypothalamic-pituitary-adrenal axis-associated brain regions

    PubMed Central

    Johnson, Lance A.; Weber, Sydney; Raber, Jacob

    2016-01-01

    Rationale Chronic methamphetamine (MA) abuse leads to dependence and symptoms of withdrawal after use has ceased. Negative mood states associated with withdrawal, as well as drug reinstatement, have been linked to drug-induced disruption of the hypothalamic-pituitary-adrenal (HPA) axis. However, effects of chronic MA exposure or acute MA exposure following withdrawal on neural activation patterns within brain regions that regulate the HPA axis are unknown. Objectives In this study, neural activation patterns were assessed by quantification of c-Fos protein in mice exposed to different regimens of MA administration. Methods (Experiment 1) Adult male mice were treated with MA (5 mg/kg) or saline once or once daily for 10 days. (Experiment 2) Mice were treated with MA or saline once daily for 10 days and following a 10-day withdrawal period were re-administered a final dose of MA or saline. c-Fos was quantified in brains after the final injection. Results (Experiment 1) Compared to exposure to a single dose of MA (5 mg/kg), chronic MA exposure decreased the number of c-Fos expressing cells in the paraventricular hypothalamus, dorsomedial hypothalamus, central amygdala, basolateral amygdala, bed nucleus of the stria terminalis (BNST), and CA3 hippocampal region. (Experiment 2) Compared to mice receiving their first dose of MA, mice chronically treated with MA, withdrawn, and re-administered MA, showed decreased c-Fos expressing cells within the central and basolateral amygdala, BNST, and CA3. Conclusions HPA axis-associated amygdala, extended amygdala, and hippocampal regions endure lasting effects following chronic MA exposure and therefore may be linked to stress-related withdrawal symptoms. PMID:26525566

  15. Dopaminergic Regulation of Mate Competition Aggression and Aromatase-Fos Colocalization in Vasotocin Neurons

    PubMed Central

    Kabelik, David; Kelly, Aubrey M.; Goodson, James L.

    2009-01-01

    Summary Recent experiments demonstrate that aggressive competition for potential mates involves different neural mechanisms than does territorial, resident-intruder aggression. However, despite the obvious importance of mate competition aggression, we know little about its regulation. Immediate early gene experiments show that in contrast to territorial aggression, mate competition in finches is accompanied by the activation of neural populations associated with affiliation and motivation, including vasotocin (VT) neurons in the medial bed nucleus of the stria terminalis (BSTm) and midbrain dopamine (DA) neurons that project to the BSTm. Although VT is known to facilitate mate competition aggression, the role of DA has not previously been examined. We now show that in male zebra finches (Taeniopygia guttata), mate competition aggression is inhibited by the D2 agonist quinpirole, though not the D1 agonist SKF-38393 or the D4 agonist PD168077. The D3 agonist 7-OH-DPAT also inhibited aggression, but only following high dose treatment that may affect aggression via non-specific binding to D2 receptors. Central VT infusion failed to restore D2 agonist-inhibited aggression in a subsequent experiment, demonstrating that D2 does not suppress aggression by inhibiting VT release from BSTm neurons. In a final experiment, we detected D2 agonist-induced increases in immunofluorescent colocalization of the product of the immediate early gene c-fos and the steroid-converting enzyme aromatase (ARO) within VT neurons of the BSTm. Thus, although VT and DA appear to influence mate competition aggression independently, BSTm VT neurons are clearly influenced by the activation of D2 receptors, which may modify future behaviors. PMID:19540858

  16. Blockade of 5-Ht3 receptors in the septal area increases Fos expression in selected brain areas.

    PubMed

    Urzedo-Rodrigues, Lilia S; Ferreira, Hilda S; Santana, Rejane Conceição; Luz, Carla Patrícia; Perrone, Camila F; Fregoneze, Josmara B

    2014-04-01

    Serotonin is widely distributed throughout the brain and is involved in a multiplicity of visceral, cognitive and behavioral responses. It has been previously shown that injections of different doses of ondansetron, a 5-HT3 receptor antagonist, into the medial septum/vertical limb of the diagonal band complex (MS/vDB) induce a hypertensive response in rats. On the other hand, administration of m-CPBG, a 5-HT3 agonist, into the MS/vDB inhibits the increase of blood pressure during restraint stress. However, it is unclear which neuronal circuitry is involved in these responses. The present study investigated Fos immunoreactive nuclei (Fos-IR) in different brain areas following the blockade of 5-HT3 receptors located in the MS/vDB in sham and in sinoaortic denervated (SAD) rats. Ondansetron injection into the MS/vDB increases Fos-IR in different brain areas including the limbic system (central amygdala and ventral part of the bed nucleus of the stria terminalis), hypothalamus (medial parvocellular parts of the paraventricular nucleus, anterodorsal preoptic area, dorsomedial hypothalamic nucleus), mesencephalon (ventrolateral periaqueductal gray region) and rhombencephalon (lateral parabrachial nucleus) in sham rats. Barodenervation results in higher Fos expression at the parvocellular and magnocellular part of the paraventricular nucleus, the lateral parabrachial nucleus, the central nucleus of amygdala, the locus coeruleus, the medial part of the nucleus of the solitary tract, the rostral ventrolateral medulla and the caudal ventrolateral medulla following 5-HT3receptor blockade in the MS/vDB. Based on the present results and previous data showing a hypertensive response to ondansetron injected into the MS/vDB, it is reasonable to suggest that 5-HT3receptors in the MS/vDB exert an inhibitory drive that may oscillate as a functional regulatory part of the complex central neuronal network participating in the control of blood pressure.

  17. Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala.

    PubMed

    Pleil, Kristen E; Lowery-Gionta, Emily G; Crowley, Nicole A; Li, Chia; Marcinkiewcz, Catherine A; Rose, Jamie H; McCall, Nora M; Maldonado-Devincci, Antoniette M; Morrow, A Leslie; Jones, Sara R; Kash, Thomas L

    2015-12-01

    Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions. Forty-eight hours after four cycles of CIE, mice were either assayed in the marble burying test (MBT) or their brains were harvested and whole-cell electrophysiological recordings were performed in the prelimbic and infralimbic medial prefrontal cortex (PLC and ILC), the lateral and medial central nucleus of the amygdala (lCeA and mCeA), and the dorsal and ventral bed nucleus of the stria terminalis (dBNST and vBNST). Ethanol-exposed mice displayed increased anxiety in the MBT compared to air-exposed controls, and alterations in neuronal function were observed in all brain structures examined, including several distinct differences between subregions within each structure. Chronic ethanol exposure induced hyperexcitability of the ILC, as well as a shift toward excitation in synaptic drive and hyperexcitability of vBNST neurons; in contrast, there was a net inhibition of the CeA. This study reveals extensive effects of chronic ethanol exposure on the basal function of cortico-limbic brain regions, suggests that there may be complex interactions between these regions in the regulation of ethanol-dependent alterations in anxiety state, and highlights the need for future examination of projection-specific effects of ethanol in cortico-limbic circuitry.

  18. Developmental changes in the acute ethanol sensitivity of glutamatergic and GABAergic transmission in the BNST.

    PubMed

    Wills, T A; Kash, T L; Winder, D G

    2013-11-01

    Glutamatergic and GABAergic transmission undergo significant changes during adolescence. Receptors for both of these transmitters (NMDAR, and GABAA) are known to be key targets for the acute effects of ethanol in adults. The current study set out to investigate the acute effects of ethanol on both NMDAR-mediated excitatory transmission and GABAergic inhibitory transmission within the bed nucleus of the stria terminalis (BNST) across age. The BNST is an area of the brain implicated in the negative reinforcing properties associated with alcohol dependence, and the BNST plays a critical role in stress-induced relapse. Therefore, assessing the developmental regulation of ethanol sensitivity in this key brain region is important to understanding the progression of ethanol dependence. To do this, whole-cell recordings of isolated NMDAR-evoked excitatory postsynaptic currents (eEPSCs) or evoked GABAergic inhibitory postsynaptic currents (eIPSCs) were performed on BNST neurons in slices from 4- or 8-week-old male C57BL/6J mice. Ethanol (50 mm) produced greater inhibition of NMDAR-eEPSCs in adolescent mice than in adult mice. This enhanced sensitivity in adolescence was not a result of shifts in function of the GluN2B subunit of the NMDAR, measured by Ro25-6981 inhibition and decay kinetics measured across age. Adolescent mice also exhibited greater ethanol sensitivity of GABAergic transmission, as ethanol (50 mm) enhanced eIPSCs in the BNST of adolescent but not adult mice. Collectively, this work illustrates that a moderate dose of ethanol produces greater inhibition of transmission in the BNST (through greater excitatory inhibition and enhancement of inhibitory transmission) in adolescents compared to adults. Given the role of the BNST in alcohol dependence, these developmental changes in acute ethanol sensitivity could accelerate neuroadaptations that result from chronic ethanol use during the critical period of adolescence.

  19. Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition.

    PubMed

    Albright, Benjamin; Dhaher, Roni; Wang, Helen; Harb, Roa; Lee, Tih-Shih W; Zaveri, Hitten; Eid, Tore

    2017-02-01

    Loss of glutamine synthetase (GS) in hippocampal astrocytes has been implicated in the causation of human mesial temporal lobe epilepsy (MTLE). However, the mechanism by which the deficiency in GS leads to epilepsy is incompletely understood. Here we ask how hippocampal GS inhibition affects seizure phenotype and neuronal activation during epilepsy development (epileptogenesis). Epileptogenesis was induced by infusing the irreversible GS blocker methionine sulfoximine (MSO) unilaterally into the hippocampal formation of rats. We then used continuous video-intracranial electroencephalogram (EEG) monitoring and c-Fos immunohistochemistry to determine the type of seizures and spatial distribution of neuronal activation early (1-5days postinfusion) and late (16-43days postinfusion) in epileptogenesis. Early in epileptogenesis, seizures were preferentially mild (stage 1-2), activating neurons in the entorhinal-hippocampal area, the basolateral amygdala, the piriform cortex, the midline thalamus, and the anterior olfactory area. Late in epileptogenesis, the seizures were generally more severe (stages 4-5) with neuronal activation extending to the neocortex, the bed nucleus of the stria terminalis, the mediodorsal thalamu\\s, and the central nucleus of the amygdala. Our findings demonstrate that inhibition of GS focally in the hippocampal formation triggers a process of epileptogenesis characterized by gradual worsening of seizure severity and involvement of progressively larger neuronal populations over a period of several weeks. Knowledge about the underlying mechanism of epileptogenesis is important because such knowledge may result in more specific and efficacious treatments of MTLE by moving away from large and poorly specific surgical resections to highly targeted surgical or pharmacological interventions of the epileptogenic process.

  20. Sex-Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin-1a Receptors.

    PubMed

    Grundwald, N J; Benítez, D P; Brunton, P J

    2016-04-01

    Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin-1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up-regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS-induced sex-dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans.

  1. Brain activation by an olfactory stimulus paired with juvenile play in female rats.

    PubMed

    Paredes-Ramos, P; McCarthy, M M; Bowers, J M; Miquel, M; Manzo, J; Coria-Avila, G A

    2014-06-22

    We have previously shown that reward experienced during social play at juvenile age can be paired with artificial odors, and later in adulthood facilitate olfactory conditioned partner preferences (PP) in female rats. Herein, we examined the expression of FOS immunoreactivity (FOS-IR) following exposure to the odor paired with juvenile play (CS+). Starting at day P31 females received daily 30-min periods of social play with lemon-scented (paired group) or unscented females (unpaired group). At day P42, they were tested for play-PP with two juvenile males, one bearing the CS+ (lemon) and one bearing a novel odor (almond). Females were ovariectomized, hormone-primed and at day P55 tested for sexual-PP between two adult stud males scented with lemon or almond. In both tests, females from the paired group displayed conditioned PP (play or sexual) toward males bearing the CS+. In the present experiments females were exposed at day P59 to the CS+ during 60 min and their brains processed for FOS-IR. One group of female rats (Play+Sex) underwent play-PP and sexual-PP, whereas a second group of females (Play-only) underwent exclusively play-PP but not sexual-PP. Results showed that in the Play-only experiment exposure to the CS+ induced more FOS-IR in the medial prefrontal cortex, orbitofrontal cortex, dorsal striatum, and ventral tegmental area as compared to females from the unpaired group. In the Play+Sex experiment, more FOS-IR was observed in the piriform cortex, dorsal striatum, lateral septum, nucleus accumbens shell, bed nucleus of the stria terminalis and medial amygdala as compared to females from the unpaired group. Taken together, these results indicate mesocorticolimbic brain areas direct the expectation and/or choice of conditioned partners in female rats. In addition, transferring the meaning of play to sex preference requires different brain areas.

  2. Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala

    PubMed Central

    Pleil, Kristen E.; Lowery-Gionta, Emily G.; Crowley, Nicole A.; Li, Chia; Marcinkiewcz, Catherine A.; Rose, Jamie H.; McCall, Nora M.; Maldonado-Devincci, Antoniette M.; Morrow, A. Leslie; Jones, Sara R.; Kash, Thomas L.

    2016-01-01

    Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions. Forty-eight hours after four cycles of CIE, mice were either assayed in the marble burying test (MBT) or their brains were harvested and whole-cell electrophysiological recordings were performed in the prelimbic and infralimbic medial prefrontal cortex (PLC and ILC), the lateral and medial central nucleus of the amygdala (lCeA and mCeA), and the dorsal and ventral bed nucleus of the stria terminalis (dBNST and vBNST). Ethanol-exposed mice displayed increased anxiety in the MBT compared to air-exposed controls, and alterations in neuronal function were observed in all brain structures examined, including several distinct differences between subregions within each structure. Chronic ethanol exposure induced hyperexcitability of the ILC, as well as a shift toward excitation in synaptic drive and hyperexcitability of vBNST neurons; in contrast, there was a net inhibition of the CeA. This study reveals extensive effects of chronic ethanol exposure on the basal function of cortico-limbic brain regions, suggests that there may be complex interactions between these regions in the regulation of ethanol-dependent alterations in anxiety state, and highlights the need for future examination of projection-specific effects of ethanol in cortico-limbic circuitry. PMID:26188147

  3. Sex Difference in Susceptibility and Resistance to Noise-Induced Hearing Loss in Chinchillas

    DTIC Science & Technology

    2000-10-01

    guinea pig and its effect on the acute cochlear toxicity of ethacrynic acid . Biochem. Pharmacol. 37:3743-3747. Lee, K.S., Kim, H.K., Moon, H.S., Hong...Harpur, E.S.. Geseher, A., 1988. Gluta- thione depletion in the guinea pig and its effect on the acute cochlear toxicity of ethacrynic acid . Biochem...potentials and enzyme activities after ethacrynic acid injection are secondary to stria vascularis ischemia. Assoc. Res. Otolaryngol. Abstr

  4. Inducing labor

    MedlinePlus

    ... inducing labor is to "break the bag of waters" or rupture the membranes. Your health care provider will do a pelvic exam and will guide a small plastic probe with a hook on the end through your cervix to create a hole in the membrane. This does not hurt you ...

  5. Exercise-Induced Bronchoconstriction

    MedlinePlus

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  6. Ion channels in basolateral membrane of marginal cells dissociated from gerbil stria vascularis.

    PubMed

    Takeuchi, S; Ando, M; Kozakura, K; Saito, H; Irimajiri, A

    1995-03-01

    The basolateral membrane of isolated strial marginal cells has been probed for conductive pathways by the patch-clamp technique. Two types of voltage-insensitive channels were identified in both cell-attached and excised patches. Of these, frequently (69% of excised patches) observed was a Ca(2+)-activated nonselective cation channel having a unit conductance of 24.9 +/- 0.5 pS (N = 16). Other characteristics of this type in excised patches include: 1) linear I-V relations with 150 mM K+ (pipette)/150 mM Na+ (bath), 2) a permeability sequence of NH4+ > Na+ = K+ = Rb+ > Li+, 3) a flickering block by quinine or quinidine (both 1 mM), and 4) a dose dependent block of its activity by ADP or ATP (IC50,ATP/IC50,ADP = 20-35), both from the cytosolic side. Channels with similar characteristics were found in the apical membrane of the same cell; however, the basolateral channels were 2-4 times more densely distributed than the apical counterparts. Also frequently (57%) detected was a Cl- channel of 80.0 +/- 0.5 pS (N = 6), whose activity was Ca2+ independent. Additionally, this Cl- channel had: 1) linear I-V relations with symmetric Cl-, 2) a permeability sequence of Cl- > Br- > I- > or = NO3- > or = gluconate-, and 3) a complete and reversible block by 1 mM diphenylamine-2-carboxylate. In contrast to the apical Cl- channels, the basolateral ones had a much higher density (57% vs. < 1%) as well as a higher unit conductance (80 pS vs. 50 pS) than the apical counterpart. The relative abundance of these two types as the major conductive pathways for Na+, K+, and Cl- in the basolateral region must be taken into account when addressing the role of strial marginal cells in generating the positive endocochlear potential. The Cl- channel may facilitate Cl- distribution across the basolateral membrane.

  7. Exercise-Induced Asthma

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Exercise-Induced Asthma KidsHealth > For Parents > Exercise-Induced Asthma ... they choose. previous continue Tips for Kids With Exercise-Induced Asthma For the most part, kids with ...

  8. Receptors for GRP/bombesin-like peptides in the rat forebrain

    SciTech Connect

    Wolf, S.S.; Moody, T.W.

    1985-01-01

    Binding sites in the rat forebrain were characterized using ( SVI-Tyr4)bombesin as a receptor probe. Pharmacology experiments indicate that gastrin releasing peptide (GRP) and the GRP fragments GRP as well as Ac-GRP inhibited radiolabeled (Tyr4)bombesin binding with high affinity. Biochemistry experiments indicated that heat, N-ethyl maleimide or trypsin greatly reduced radiolabeled (Tyr4)bombesin binding. Also, autoradiographic studies indicated that highest grain densities were present in the stria terminalis, periventricular and suprachiasmatic nucleus of the hypothalamus, dorsomedial and rhomboid thalamus, dentate gyrus, hippocampus and medial amygdaloid nucleus. The data suggest that CNS protein receptors, which are discretely distributed in the rat forebrain, may mediate the action of endogenous GRP/bombesin-like peptides.

  9. AgRP Neural Circuits Mediate Adaptive Behaviors in the Starved State

    PubMed Central

    Padilla, Stephanie L.; Qiu, Jian; Soden, Marta E.; Sanz, Elisenda; Nestor, Casey C; Barker, Forrest D.; Quintana, Albert; Zweifel, Larry S.; Rønnekleiv, Oline K.; Kelly, Martin J.; Palmiter, Richard D.

    2016-01-01

    In the face of starvation animals will engage in high-risk behaviors that would normally be considered maladaptive. Starving rodents for example will forage in areas that are more susceptible to predators and will also modulate aggressive behavior within a territory of limited or depleted nutrients. The neural basis of these adaptive behaviors likely involves circuits that link innate feeding, aggression, and fear. Hypothalamic AgRP neurons are critically important for driving feeding and project axons to brain regions implicated in aggression and fear. Using circuit-mapping techniques, we define a disynaptic network originating from a subset of AgRP neurons that project to the medial nucleus of the amygdala and then to the principle bed nucleus of the stria terminalis, which plays a role in suppressing territorial aggression and reducing contextual fear. We propose that AgRP neurons serve as a master switch capable of coordinating behavioral decisions relative to internal state and environmental cues. PMID:27019015

  10. Pituitary adenylate cyclase activating polypeptide in stress-related disorders: data convergence from animal and human studies

    PubMed Central

    May, Victor

    2014-01-01

    The maladaptive expression and function of several stress-associated hormones have been implicated in pathological stress- and anxiety-related disorders. Among these, recent evidence has suggested that pituitary adenylate cyclase activating polypeptide (PACAP) has critical roles in central neurocircuits mediating stress-related emotional behaviors. We describe the PACAPergic systems, the data implicating PACAP in stress biology and how altered PACAP expression and signaling may result in psychopathologies. We include our work implicating PACAP signaling within the bed nucleus of the stria terminalis (BNST) in mediating the consequences of stressor exposure and relatedly, describe more recent studies suggesting that PACAP in the central nucleus of the amygdala (CeA) may impact the emotional aspects of chronic pain states. In aggregate, these results are consistent with data suggesting that PACAP dysregulation is associated with post-traumatic stress disorder (PTSD) in humans. PMID:25636177

  11. Autoradiographic visualization of CNS receptors for vasoactive intestinal peptide

    SciTech Connect

    Shaffer, M.M.; Moody, T.W.

    1986-03-01

    Receptors for VIP were characterized in the rat CNS. /sup 125/I-VIP bound with high affinity to rat brain slices. Binding was time dependent and specific. Pharmacology studies indicated that specific /sup 125/I-VIP binding was inhibited with high affinity by VIP and low affinity by secretin and PHI. Using in vitro autoradiographic techniques high grain densities were present in the dentate gyrus, pineal gland, supraoptic and suprachiasmatic nuclei, superficial gray layer of the superior colliculus and the area postrema. Moderate grain densities were present in the olfactory bulb and tubercle, cerebral cortex, nucleus accumbens, caudate putamen, interstitial nucleus of the stria terminalis, paraventricular thalamic nucleus, medial amygdaloid nucleus, subiculum and the medial geniculate nucleus. Grains were absent in the corpus callosum and controls treated with 1 microM unlabeled VIP. The discrete regional distribution of VIP receptors suggest that it may function as an important modulator of neural activity in the CNS.

  12. A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster).

    PubMed

    Sullivan, Alana W; Beach, Elsworth C; Stetzik, Lucas A; Perry, Amy; D'Addezio, Alyssa S; Cushing, Bruce S; Patisaul, Heather B

    2014-10-01

    Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.

  13. Lesions in the medial posterior region of the BST impair sexual behavior in sexually experienced and inexperienced male rats.

    PubMed

    Claro, F; Segovia, S; Guilamón, A; Del Abril, A

    1995-01-01

    Previous studies have showed that lesions in the bed nucleus of the stria terminalis of experienced male rats impair some parameters of sexual behavior. The aim of this study was to examine the contribution of the medial posterior region of the bed nucleus of the stria terminalis (BSTMP), a sexually dimorphic region of this nucleus that pertains to the vomeronasal system, to the modulation of sexual behavior of the male rat. Small electrolytic bilateral lesions in the BSTMP were made in male heterosexual experienced and inexperienced rats. Sham lesioned animals were also tested as a control of the effects of the general surgical procedures. Behavioral tests were then performed to obtain standard measures of masculine sexual behavior. Our results indicate that the sexually experienced male rats with lesioned BSTMPs showed increases in the number of mounts and the number of intromissions and, consequently, in ejaculation latency. In contrast, the sexually naive male rats showed increases in first mount and intromission latencies and in ejaculation latency, but the latter occurred due to increases in the interintromission intervals. This group also showed low correlations between olfactory investigation of the anogenital area of the female and initiation and maintenance of copulatory behavior. The results suggest that sexual experience obtained in the very artificial conditions of laboratory tests could supply some of the cues provided by the BSTMP in the process of sensorial integration, which we hypothesize modulates the initiation and pacing of copulation. However, sexual experience does not apparently supply any other kinds of cues provided or processed in the BSTMP that are involved in modulating the elicitation of intromissions and ejaculations.

  14. Early Life Manipulations of the Nonapeptide System Alter Pair Maintenance Behaviors and Neural Activity in Adult Male Zebra Finches

    PubMed Central

    Baran, Nicole M.; Tomaszycki, Michelle L.; Adkins-Regan, Elizabeth

    2016-01-01

    Adult zebra finches (T. guttata) form socially monogamous pair bonds characterized by proximity, vocal communication, and contact behaviors. In this experiment, we tested whether manipulations of the nonapeptide hormone arginine vasotocin (AVT, avian homolog of vasopressin) and the V1a receptor (V1aR) early in life altered species-typical pairing behavior in adult zebra finches of both sexes. Although there was no effect of treatment on the tendency to pair in either sex, males in different treatments exhibited profoundly different profiles of pair maintenance behavior. Following a brief separation, AVT-treated males were highly affiliative with their female partner but sang very little compared to Controls. In contrast, males treated with a V1aR antagonist sang significantly less than Controls, but did not differ in affiliation. These effects on behavior in males were also reflected in changes in the expression of V1aR and immediate early gene activity in three brain regions known to be involved in pairing behavior in birds: the medial amygdala, medial bed nucleus of the stria terminalis, and the lateral septum. AVT males had higher V1aR expression in the medial amygdala than both Control and antagonist-treated males and immediate early gene activity of V1aR neurons in the medial amygdala was positively correlated with affiliation. Antagonist treated males showed decreased activity in the medial amygdala. In addition, there was a negative correlation between the activity of V1aR cells in the medial bed nucleus of the stria terminalis and singing. Treatment also affected the expression of V1aR and activity in the lateral septum, but this was not correlated with any behaviors measured. These results provide evidence that AVT and V1aR play developmental roles in specific pair maintenance behaviors and the neural substrate underlying these behaviors in a bird. PMID:27065824

  15. Distribution of secretagogin-containing neurons in the basal forebrain of mice, with special reference to the cholinergic corticopetal system.

    PubMed

    Gyengesi, Erika; Andrews, Zane B; Paxinos, George; Zaborszky, Laszlo

    2013-05-01

    Cholinergic and GABAergic corticopetal neurons in the basal forebrain play important roles in cortical activation, sensory processing, and attention. Cholinergic neurons are intermingled with peptidergic, and various calcium binding protein-containing cells, however, the functional role of these neurons is not well understood. In this study we examined the expression pattern of secretagogin (Scgn), a newly described calcium-binding protein, in neurons of the basal forebrain. We also assessed some of the corticopetal projections of Scgn neurons and their co-localization with choline acetyltransferase (ChAT), neuropeptide-Y, and other calcium-binding proteins (i.e., calbindin, calretinin, and parvalbumin). Scgn is expressed in cell bodies of the medial and lateral septum, vertical and horizontal diagonal band nuclei, and of the extension of the amygdala but it is almost absent in the ventral pallidum. Scgn is co-localized with ChAT in neurons of the bed nucleus of the stria terminalis, extension of the amygdala, and interstitial nucleus of the posterior limb of the anterior commissure. Scgn was co-localized with calretinin in the accumbens nucleus, medial division of the bed nucleus of stria terminalis, the extension of the amygdala, and interstitial nucleus of the posterior limb of the anterior commissure. We have not found co-expression of Scgn with parvalbumin, calbindin, or neuropeptide-Y. Retrograde tracing studies using Fluoro Gold in combination with Scgn-specific immunohistochemistry revealed that Scgn neurons situated in the nucleus of the horizontal limb of the diagonal band project to retrosplenial and cingulate cortical areas.

  16. Neuronal architecture in the rat central nucleus of the amygdala: a cytological, hodological, and immunocytochemical study.

    PubMed

    Cassell, M D; Gray, T S; Kiss, J Z

    1986-04-22

    The organization of neurons in the rat central nucleus of the amygdala (CNA) has been examined by using Nissl stain and immunocytochemical and retrograde tracing techniques. Four main subdivisions were identified on the basis of quantitative analyses of Nissl-stained material: medial (CM), lateral (CL), lateral capsular (CLC), and ventral (CV). An intermediate subdivision (CI), previously described by McDonald ('82), was apparent only in animals that had HRP-WGA injected into the bed nucleus of the stria terminalis. Large populations of neurotensin-, corticotropin-releasing factor (CRF)-, and enkephalin-immunoreactive neurons were present within the lateral divisions (mainly CL), although they were also seen within CM. Somatostatin-immunoreactive neurons were distributed mainly within CL and CM. Within CL, neurotensin- and enkephalin-immunoreactive neurons were more numerous laterally whereas CRF- and somatostatin-immunoreactive neurons were more numerous medially. Substance P-immunoreactive neurons were almost exclusively confined to CM. Only a few cholecystokinin- and vasoactive-polypeptide-immunoreactive neurons were seen in the CNA, and they were observed within CL, CV, and CM. The majority of neurons projecting to the dorsal medulla, hypothalamus, and ventral tegmental area were located within CM, although a significant number of cells were also seen within CL. Efferent projections to the bed nucleus of the stria terminalis were found to arise from neurons located within all subdivisions of the CNA. Thus, the distributional patterns of peptidergic and efferent neurons were not confined to individual cytoarchitectonically- defined subdivisions of the CNA. Rather, the results suggest overlapping medial to the lateral trends. Comparisons with the results of previous studies indicate that peptidergic and afferent terminal distribution patterns are more restricted to individual cytoarchitectonically defined subregions of the CNA. These observations suggest that the

  17. Localization of myocyte enhancer factor 2 in the rodent forebrain: regionally-specific cytoplasmic expression of MEF2A.

    PubMed

    Neely, M Diana; Robert, Elizabeth M; Baucum, Anthony J; Colbran, Roger J; Muly, E Chris; Deutch, Ariel Y

    2009-06-05

    The transcription factor myocyte enhancer factor 2 (MEF2) is expressed throughout the central nervous system, where four MEF2 isoforms play important roles in neuronal survival and differentiation and in synapse formation and maintenance. It is therefore somewhat surprising that there is a lack of detailed information on the localization of MEF2 isoforms in the mammalian brain. We have analyzed the regional, cellular, and subcellular expression of MEF2A and MEF2D in the rodent brain. These two MEF2 isoforms were co-expressed in virtually all neurons in the cortex and the striatum, but were not detected in astrocytes. MEF2A and MEF2D were localized to the nuclei of neurons in many forebrain areas, consistent with their roles as transcriptional regulators. However, in several subcortical sites we observed extensive cytoplasmic expression of MEF2A but not MEF2D. MEF2A was particularly enriched in processes of neurons in the lateral septum and bed nucleus of the stria terminalis, as well as in several other limbic sites, including the central amygdala and paraventricular nuclei of the hypothalamus and thalamus. Ultrastructural examination similarly revealed MEF2A-ir in axons and dendrites as well as MEF2A-ir nuclei in the lateral septum and bed nucleus of the stria terminalis neurons. This study demonstrates for the first time extensive cytoplasmic localization of a MEF2 transcription factor in the mammalian brain in vivo. The extranuclear localization of MEF2A suggests novel roles for MEF2A in specific neuronal populations.

  18. Convergence of olfactory and vomeronasal projections in the rat basal telencephalon.

    PubMed

    Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Ubeda-Bañon, Isabel; Del Mar Arroyo-Jimenez, Maria; Marcos, Pilar; Artacho-Pérula, Emilio; Crespo, Carlos; Insausti, Ricardo; Martinez-Marcos, Alino

    2007-10-01

    Olfactory and vomeronasal projections have been traditionally viewed as terminating in contiguous non-overlapping areas of the basal telencephalon. Original reports, however, described areas such as the anterior medial amygdala where both chemosensory afferents appeared to overlap. We addressed this issue by injecting dextran amines in the main or accessory olfactory bulbs of rats and the results were analyzed with light and electron microscopes. Simultaneous injections of different fluorescent dextran amines in the main and accessory olfactory bulbs were performed and the results were analyzed using confocal microscopy. Similar experiments with dextran amines in the olfactory bulbs plus FluoroGold in the bed nucleus of the stria terminalis indicate that neurons projecting through the stria terminalis could be integrating olfactory and vomeronasal inputs. Retrograde tracing experiments using FluoroGold or dextran amines confirm that areas of the rostral basal telencephalon receive inputs from both the main and accessory olfactory bulbs. While both inputs clearly converge in areas classically considered olfactory-recipient (nucleus of the lateral olfactory tract, anterior cortical amygdaloid nucleus, and cortex-amygdala transition zone) or vomeronasal-recipient (ventral anterior amygdala, bed nucleus of the accessory olfactory tract, and anteroventral medial amygdaloid nucleus), segregation is virtually complete at posterior levels such as the posteromedial and posterolateral cortical amygdalae. This provides evidence that areas so far considered receiving a single chemosensory modality are likely sites for convergent direct olfactory and vomeronasal inputs. Therefore, areas of the basal telencephalon should be reclassified as olfactory, vomeronasal, or mixed chemosensory structures, which could facilitate understanding of olfactory-vomeronasal interactions in functional studies.

  19. Efferent connections of the "olfactostriatum": a specialized vomeronasal structure within the basal ganglia of snakes.

    PubMed

    Martinez-Marcos, Alino; Ubeda-Bañon, Isabel; Lanuza, Enrique; Halpern, Mimi

    2005-05-01

    The olfactostriatum is a portion of the basal ganglia of snakes that receives substantial vomeronasal afferents through projections from the nucleus sphericus. In a preceding article, the olfactostriatum of garter snakes (Thamnophis sirtalis) was characterized on the basis of chemoarchitecture (distribution of serotonin, neuropeptide Y and tyrosine hydroxylase) and pattern of afferent connections [Martinez-Marcos, A., Ubeda-Banon, I., Lanuza, E., Halpern, M., 2005. Chemoarchitecture and afferent connections of the "olfactostriatum": a specialized vomeronasal structure within the basal ganglia of snakes. J. Chem. Neuroanat. 29, 49-69]. In the present study, its efferent connections have been investigated. The olfactostriatum projects to the main and accessory olfactory bulbs, lateral cortex, septal complex, ventral pallidum, external, ventral anterior and dorsolateral amygdalae, bed nucleus of the stria terminalis, preoptic area, lateral posterior hypothalamic nucleus, ventral tegmental area, substantia nigra and raphe nuclei. Tracer injections in the nucleus accumbens proper, a structure closely associated with the olfactostriatum, result in a similar pattern of efferent connections with the exception of those reaching the main and accessory olfactory bulbs, lateral cortex, external, ventral anterior and dorsolateral amygdalae and bed nucleus of the stria terminalis. These data, therefore, help to characterize the olfactostriatum, an apparently specialized area of the nucleus accumbens. Double labeling experiments after tracer injections in the nucleus sphericus and the lateral posterior hypothalamic nucleus demonstrate a pathway between these two structures through the olfactostriatum. Injections in the olfactostriatum and in the medial amygdala show parallel projections to the lateral posterior hypothalamic nucleus. Since this hypothalamic nucleus has been previously described as projecting to the hypoglossal nucleus, both, the medial amygdala and the

  20. The extended amygdala and salt appetite

    NASA Technical Reports Server (NTRS)

    Johnson, A. K.; de Olmos, J.; Pastuskovas, C. V.; Zardetto-Smith, A. M.; Vivas, L.

    1999-01-01

    Both chemo- and mechanosensitive receptors are involved in detecting changes in the signals that reflect the status of body fluids and of blood pressure. These receptors are located in the systemic circulatory system and in the sensory circumventricular organs of the brain. Under conditions of body fluid deficit or of marked changes in fluid distribution, multiple inputs derived from these humoral and neural receptors converge on key areas of the brain where the information is integrated. The result of this central processing is the mobilization of homeostatic behaviors (thirst and salt appetite), hormone release, autonomic changes, and cardiovascular adjustments. This review discusses the current understanding of the nature and role of the central and systemic receptors involved in the facilitation and inhibition of thirst and salt appetite and on particular components of the central neural network that receive and process input derived from fluid- and cardiovascular-related sensory systems. Special attention is paid to the structures of the lamina terminalis, the area postrema, the lateral parabrachial nucleus, and their association with the central nucleus of the amygdala and the bed nucleus of the stria terminalis in controlling the behaviors that participate in maintaining body fluid and cardiovascular homeostasis.

  1. Progesterone receptor in the forebrain of female gray short-tailed opossums: effects of exposure to male stimuli.

    PubMed

    Vitazka, Maria E; Cárdenas, Horacio; Cruz, Yolanda; Fadem, Barbara H; Norfolk, Jennifer R; Harder, John D

    2009-01-01

    Progesterone receptor immunoreactivity (PRir) in brain areas involved in reproductive behavior in eutherian species was examined for the first time in a female marsupial, the gray short-tailed opossum (Monodelphis domestica, hereinafter, opossum). PRir in nuclei of neurons, measured as area covered by stained nuclei, was seen in the arcuate nucleus (Arc); anteroventral periventricular nucleus (AVPv); bed nucleus of the stria terminalis (BST); medial preoptic area (MPOA), and ventromedial hypothalamus (VMH), but not in control areas adjacent to the hypothalamus or cortex. Female opossums are induced into cytological, urogenital sinus (UGS), estrus by male pheromones and into behavioral estrus, i.e., receptivity, by pairing with a male, and both estradiol (E) and progesterone (P) are involved in induction of receptivity in intact and ovariectomized females. PRir in the AVPv, MPOA, and VMH was very low in females that had never been exposed to males or their scent marks, i.e., naïve anestrous (NVA) females, and either previous or current exposure to males or their scent marks was associated with elevated PRir. PRir was significantly higher in the AVPv and MPOA of anestrous females with previous but no current exposure to males and their scent marks, i.e., experienced anestrous (EXPA) females, than in NVA females, but PRir was significantly lower in the MPOA and VMH of EXPA females than in females that were behaviorally receptive and had recently copulated, i.e., behavioral receptive estrous (BRE) females. PRir was higher in the VMH of both UGS estrous (UGSE) and BRE females compared to that in EXPA animals, but PRir did not differ between UGSE and BRE females in any of the 3 brain areas examined, including the MPOA These results provide evidence that pheromonal induction of estrus and sexual receptivity in opossums is associated with elevation of PRir in the VMH and MPOA and that prior exposure to males or their pheromones, even in the absence of current male stimuli

  2. Cavitation-resistant inducer

    DOEpatents

    Dunn, Charlton; Subbaraman, Maria R.

    1989-01-01

    An improvement in an inducer for a pump wherein the inducer includes a hub, a plurality of radially extending substantially helical blades and a wall member extending about and encompassing an outer periphery of the blades. The improvement comprises forming adjacent pairs of blades and the hub to provide a substantially rectangular cross-sectional flow area which cross-sectional flow area decreases from the inlet end of the inducer to a discharge end of the inducer, resulting in increased inducer efficiency improved suction performance, reduced susceptibility to cavitation, reduced susceptibility to hub separation and reduced fabrication costs.

  3. Cavitation-resistant inducer

    DOEpatents

    Dunn, C.; Subbaraman, M.R.

    1989-06-13

    An improvement in an inducer for a pump is disclosed wherein the inducer includes a hub, a plurality of radially extending substantially helical blades and a wall member extending about and encompassing an outer periphery of the blades. The improvement comprises forming adjacent pairs of blades and the hub to provide a substantially rectangular cross-sectional flow area which cross-sectional flow area decreases from the inlet end of the inducer to a discharge end of the inducer, resulting in increased inducer efficiency improved suction performance, reduced susceptibility to cavitation, reduced susceptibility to hub separation and reduced fabrication costs. 11 figs.

  4. Fos Expression in Rat Brain During Depletion-Induced Thirst and Salt Appetite

    NASA Technical Reports Server (NTRS)

    Thunhorst, R. L.; Xu, Z.; Cicha, M. Z.; Zardetto-Smith, A. M.; Johnson, A. K.

    1998-01-01

    The expression of Fos protein (Fos immunoreactivity, Fos-ir) was mapped in the brain of rats subjected to an angiotensin-dependent model of thirst and salt appetite. The physiological state associated with water and sodium ingestion was produced by the concurrent subcutaneous administration of the diuretic furosemide (10 mg/kg) and a low dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (5 mg/kg; Furo/Cap treatment). The animals were killed 2 h posttreatment, and the brains were processed for Fos-ir to assess neural activation. Furo/Cap treatment significantly increased Fos-ir density above baseline levels both in structures of the lamina terminalis and hypothalamus known to mediate the actions of ANG 2 and in hindbrain regions associated with blood volume and pressure regulation. Furo/Cap treatment also typically increased Fos-ir density in these structures above levels observed after administration of furosemide or captopril separately. Fos-ir was reduced to a greater extent in forebrain than in hindbrain areas by a dose of captopril (100 mg/kg sc) known to block the actions of ACE in the brain. The present work provides further evidence that areas of lamina terminalis subserve angiotensin-dependent thirst and salt appetite.

  5. Flumazenil-induced ballism.

    PubMed

    Kim, Joong-Seok; Ko, Seok-Bum; Choi, Yeong-Bin; Lee, Kwang-Soo

    2003-04-01

    Flumazenil, an imidazobenzodiazepine, is the first benzodiazepine antagonist and is being used to reverse the adverse pharmacological effects of benzodiazepine. There have been a few reports on the central nevous system side effects with its use. We report a patient with generalized ballism following administration of flumazenil. The mechanism through which flumazenil induced this symptom is unknown. It is conceivable that flumazenil may antagonize the GABA-benzodiazepine receptor complex and induce dopamine hypersensitivity, thus induce dyskinesic symptoms.

  6. Flumazenil-induced ballism.

    PubMed Central

    Kim, Joong-Seok; Ko, Seok-Bum; Choi, Yeong-Bin; Lee, Kwang-Soo

    2003-01-01

    Flumazenil, an imidazobenzodiazepine, is the first benzodiazepine antagonist and is being used to reverse the adverse pharmacological effects of benzodiazepine. There have been a few reports on the central nevous system side effects with its use. We report a patient with generalized ballism following administration of flumazenil. The mechanism through which flumazenil induced this symptom is unknown. It is conceivable that flumazenil may antagonize the GABA-benzodiazepine receptor complex and induce dopamine hypersensitivity, thus induce dyskinesic symptoms. PMID:12692435

  7. Drug-induced nephropathies.

    PubMed

    Paueksakon, Paisit; Fogo, Agnes B

    2017-01-01

    Drugs are associated frequently with the development of various types of acute and chronic kidney diseases. Nephrotoxicity is associated most commonly with injury in the tubulointerstitial compartment manifested as either acute tubular injury or acute interstitial nephritis. A growing number of reports has also highlighted the potential for drug-induced glomerular disease, including direct cellular injury and immune-mediated injury. Recognition of drug-induced nephropathies and rapid discontinuation of the offending agents are critical to maximizing the likelihood of renal function recovery. This review will focus on the pathology and pathogenesis of drug-induced acute interstitial nephritis and drug-induced glomerular diseases.

  8. Teacher-Induced Errors.

    ERIC Educational Resources Information Center

    Richmond, Kent C.

    Students of English as a second language (ESL) often come to the classroom with little or no experience in writing in any language and with inaccurate assumptions about writing. Rather than correct these assumptions, teachers often seem to unwittingly reinforce them, actually inducing errors into their students' work. Teacher-induced errors occur…

  9. Stress-induced flowering

    PubMed Central

    Wada, Kaede C

    2010-01-01

    Many plant species can be induced to flower by responding to stress factors. The short-day plants Pharbitis nil and Perilla frutescens var. crispa flower under long days in response to the stress of poor nutrition or low-intensity light. Grafting experiments using two varieties of P. nil revealed that a transmissible flowering stimulus is involved in stress-induced flowering. The P. nil and P. frutescens plants that were induced to flower by stress reached anthesis, fruited and produced seeds. These seeds germinated, and the progeny of the stressed plants developed normally. Phenylalanine ammonialyase inhibitors inhibited this stress-induced flowering, and the inhibition was overcome by salicylic acid (SA), suggesting that there is an involvement of SA in stress-induced flowering. PnFT2, a P. nil ortholog of the flowering gene FLOWERING LOCUS T (FT) of Arabidopsis thaliana, was expressed when the P. nil plants were induced to flower under poor-nutrition stress conditions, but expression of PnFT1, another ortholog of FT, was not induced, suggesting that PnFT2 is involved in stress-induced flowering. PMID:20505356

  10. Space Station Induced Monitoring

    NASA Technical Reports Server (NTRS)

    Spann, James F. (Editor); Torr, Marsha R. (Editor)

    1988-01-01

    This report contains the results of a conference convened May 10-11, 1988, to review plans for monitoring the Space Station induced environment, to recommend primary components of an induced environment monitoring package, and to make recommendations pertaining to suggested modifications of the Space Station External Contamination Control Requirements Document JSC 30426. The contents of this report are divided as Follows: Monitoring Induced Environment - Space Station Work Packages Requirements, Neutral Environment, Photon Emission Environment, Particulate Environment, Surface Deposition/Contamination; and Contamination Control Requirements.

  11. Mania Induced by Opipramol

    PubMed Central

    Firoz, Kazhungil; Khaleel, Asfia; Rajmohan, V; Kumar, Manoj; Raghuram, TM

    2015-01-01

    Antidepressants have propensity to induce manic switch in patients with bipolar disorder. Opipramol is an atypical anxiolytic and antidepressant drug which predominantly acts on sigma receptors. Although structurally resembles tricyclic antidepressant imipramine it does not have inhibitory action on the reuptake of norepinephrine/serotonin and hence it is not presumed to cause manic switch in bipolar depression. Here, we describe a case of mania induced by opipramol, in a patient with bipolar affective disorder who was treated for moderate depressive episode with lithium and opipramol and we discuss neurochemical hypothesis of opipramol-induced mania. PMID:25722522

  12. Drug-induced catatonia.

    PubMed

    Duggal, Harpreet S; Singh, Ira

    2005-09-01

    Catatonia is a heterogeneous syndrome that varies in etiology, presentation, course and sequelae. Initially conceptualized as a subtype of schizophrenia, catatonia is now recognized to occur not only with other psychiatric conditions but also with medical conditions and drug-induced and toxic states. While drug-induced catatonia is now a recognized entity, most studies club it with catatonia due to general medical conditions or organic catatonia, thus precluding any meaningful interpretation of such cases. The literature on drug-induced catatonia mostly draws from scattered case reports. This article attempts to review the available literature in this realm and integrate the information in an attempt to explore the epidemiology, etiology, mechanism and treatment of drug-induced catatonia.

  13. Exercise-induced asthma

    MedlinePlus

    Wheezing - exercise-induced; Reactive airway disease - exercise ... Having asthma symptoms when you exercise does not mean you cannot or should not exercise. But be aware of your EIA triggers. Cold or dry air may ...

  14. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  15. Vitiligo, drug induced (image)

    MedlinePlus

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  16. Statin induced myotoxicity.

    PubMed

    Sathasivam, Sivakumar

    2012-06-01

    Statins are an effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, myotoxicity induced by statins is a common adverse event and a major barrier to maximising cardiovascular risk reduction. The clinical spectrum of statin induced myotoxicity includes asymptomatic rise in creatine kinase concentration, myalgia, myositis and rhabdomyolysis. In certain cases, the cessation of statin therapy does not result in the resolution of muscular symptoms or the normalization of creatine kinase, raising the possibility of necrotizing autoimmune myopathy. There is increasing understanding and recognition of the pathophysiology and risk factors of statin induced myotoxicity. Careful history and physical examination in conjunction with selected investigations such as creatine kinase measurement, electromyography and muscle biopsy in appropriate clinical scenario help diagnose the condition. The management of statin induced myotoxicity involves statin cessation, the use of alternative lipid lowering agents or treatment regimes, and in the case of necrotizing autoimmune myopathy, immunosuppression.

  17. Glucocorticoid-induced osteonecrosis.

    PubMed

    Weinstein, Robert S

    2012-04-01

    Awareness of the need for prevention of glucocorticoid-induced fractures is growing, but glucocorticoid administration is often overlooked as the most common cause of nontraumatic osteonecrosis. Glucocorticoid-induced osteonecrosis develops in 9-40% of patients receiving long-term therapy although it may also occur with short-term exposure to high doses, after intra-articular injection, and without glucocorticoid-induced osteoporosis. The name, osteonecrosis, is misleading because the primary histopathological lesion is osteocyte apoptosis. Apoptotic osteocytes persist because they are anatomically unavailable for phagocytosis and, with glucocorticoid excess, decreased bone remodeling retards their replacement. Glucocorticoid-induced osteocyte apoptosis, a cumulative and unrepairable defect, uniquely disrupts the mechanosensory function of the osteocyte-lacunar-canalicular system and thus starts the inexorable sequence of events leading to collapse of the femoral head. Current evidence indicates that bisphosphonates may rapidly reduce pain, increase ambulation, and delay joint collapse in patients with osteonecrosis.

  18. Ethionamide-induced Pellagra.

    PubMed

    Gupta, Yashashree; Shah, Ira

    2015-08-01

    Pellagra is a disorder characterized by dermatitis, diarrhea, dementia and eventually death, resulting from a deficiency of niacin or its precursor tryptophan. Ethionamide (a second-line antituberculosis agent)-induced pellagra is rarely encountered in clinical practice. Prompt diagnosis and treatment with nicotinamide can prevent life-threatening complications. To date, only three cases have been reported. We report a 13-year-old girl presenting with ethionamide-induced pellagra that resolved after the administration of niacin.

  19. Levodopa-induced myoclonus.

    PubMed

    Klawans, H L; Goetz, C; Bergen, D

    1975-05-01

    Twelve parkinsonian patients on long-term levodopa therapy developed intermittent, myoclonic body jerks. The movements consisted of single unilateral or bilateral abrupt jerks of the extremities and occurred most frequently during sleep. Although directly related to daily dosage of levodopa, the myoclonus was specifically blocked by the serotonin antagonist, methysergide. Levodopa-induced myoclonus may be related to intermittent increases of activity of serotonin in the brain and results from levodopa-induced dysregulation of serotonin activity.

  20. Induced polarization response of microbial induced sulfideprecipitation

    SciTech Connect

    Ntarlagiannis, Dimitrios; Williams, Kenneth Hurst; Slater, Lee; Hubbard, Susan

    2004-06-04

    A laboratory scale experiment was conducted to examine the use of induced polarization and electrical conductivity to monitor microbial induced sulfide precipitation under anaerobic conditions in sand filled columns. Three columns were fabricated; one for electrical measurements, one for geochemical sampling and a third non-inoculated column was used as a control. A continual upward flow of nutrients and metals in solution was established in each column. Desulfovibrio vulgaris microbes were injected into the middle of the geochemical and electrical columns. Iron and zinc sulfides precipitated along a microbial action front as a result of sulfate reduction due by Desulfovibrio vulgaris. The precipitation front initially developed near the microbial injection location, and subsequently migrated towards the nutrient inlet, as a result of chemotaxis by Desulfovibrio vulgaris. Sampling during and subsequent to the experiment revealed spatiotemporal changes in the biogeochemical measurements associated with microbial sulfate reduction. Conductivity measurements were insensitive to all biogeochemical changes occurred within the column. Changes in the IP response (of up to 14 mrad)were observed to coincide in place and in time with the active microbe respiration/sulfide precipitation front as determined from geochemical sampling. The IP response is correlated with the lactate concentration gradient, an indirect measurement of microbial metabolism, suggesting the potential of IP as a method for monitoring microbial respiration/activity. Post experimental destructive sample analysis and SEM imaging verified the geochemical results and supported our hypothesis that microbe induced sulfide precipitation is directly detectable using electrical methods. Although the processes not fully understood, the IP response appears to be sensitive to this anaerobic microbial precipitation, suggesting a possible novel application for the IP method.

  1. Gravitationally induced quantum transitions

    NASA Astrophysics Data System (ADS)

    Landry, A.; Paranjape, M. B.

    2016-06-01

    In this paper, we calculate the probability for resonantly inducing transitions in quantum states due to time-dependent gravitational perturbations. Contrary to common wisdom, the probability of inducing transitions is not infinitesimally small. We consider a system of ultracold neutrons, which are organized according to the energy levels of the Schrödinger equation in the presence of the Earth's gravitational field. Transitions between energy levels are induced by an oscillating driving force of frequency ω . The driving force is created by oscillating a macroscopic mass in the neighborhood of the system of neutrons. The neutron lifetime is approximately 880 sec while the probability of transitions increases as t2. Hence, the optimal strategy is to drive the system for two lifetimes. The transition amplitude then is of the order of 1.06 ×10-5, and hence with a million ultracold neutrons, one should be able to observe transitions.

  2. Radiation-induced gliomas

    PubMed Central

    Prasad, Gautam; Haas-Kogan, Daphne A.

    2013-01-01

    Radiation-induced gliomas represent a relatively rare but well-characterized entity in the neuro-oncologic literature. Extensive retrospective cohort data in pediatric populations after therapeutic intracranial radiation show a clearly increased risk in glioma incidence that is both patient age- and radiation dose/volume-dependent. Data in adults are more limited but show heightened risk in certain groups exposed to radiation. In both populations, there is no evidence linking increased risk associated with routine exposure to diagnostic radiation. At the molecular level, recent studies have found distinct genetic differences between radiation-induced gliomas and their spontaneously-occurring counterparts. Clinically, there is understandable reluctance on the part of clinicians to re-treat patients due to concern for cumulative neurotoxicity. However, available data suggest that aggressive intervention can lead to improved outcomes in patients with radiation-induced gliomas. PMID:19831840

  3. Drug-induced mania.

    PubMed

    Peet, M; Peters, S

    1995-02-01

    Mania can occur by chance association during drug treatment, particularly in patients predisposed to mood disorder. Single case reports are unreliable, and evidence must be sought from large series of treated patients, particularly those with a matched control group. Drugs with a definite propensity to cause manic symptoms include levodopa, corticosteroids and anabolic-androgenic steroids. Antidepressants of the tricyclic and monoamine oxidase inhibitor classes can induce mania in patients with pre-existing bipolar affective disorder. Drugs which are probably capable of inducing mania, but for which the evidence is less scientifically secure, include other dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine and phencyclidine. Other drugs may induce mania rarely and idiosyncratically. Management involves discontinuation or dosage reduction of the suspected drug, if this is medically possible, and treatment of manic symptoms with antipsychotic drugs or lithium.

  4. Crystalglobulin-induced nephropathy.

    PubMed

    Gupta, Vinay; El Ters, Mireille; Kashani, Kianoush; Leung, Nelson; Nasr, Samih H

    2015-03-01

    Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy.

  5. Geomagnetism and induced voltage

    NASA Astrophysics Data System (ADS)

    Abdul-Razzaq, W.; Biller, R. D.

    2010-07-01

    Introductory physics laboratories have seen an influx of conceptual integrated science over time in their classrooms with elements of other sciences such as chemistry, biology, Earth science, and astronomy. We describe a laboratory to introduce this development, as it attracts attention to the voltage induced in the human brain as it is initiated by the change in the magnetic flux due to the Earth's magnetic field and movement. This simple and enjoyable experiment will demonstrate how basic concepts in physics and geology can help us think about possible health effects due to the induced voltage.

  6. Surgery induced immunosuppression.

    PubMed

    Hogan, Brian V; Peter, Mark B; Shenoy, Hrishikesh G; Horgan, Kieran; Hughes, Thomas A

    2011-02-01

    Surgery and anaesthesia result in a variety of metabolic and endocrine responses, which result in a generalised state of immunosuppression in the immediate post-operative period. Surgery induced immunosuppression has been implicated in the development of post-operative septic complications and tumour metastasis formation. In addition the effectiveness of many treatments in the adjuvant setting is dependent on a functioning immune system. By understanding the mechanisms contributing to surgery-induced immunosuppression, surgeons may undertake strategies to minimise its effect and reduce potential short-term and long-term consequences to patients.

  7. Olmesartan-Induced Enteropathy

    PubMed Central

    Adike, Abimbola; Corral, Juan; Rybnicek, David; Sussman, Daniel; Shah, Samir; Quigley, Eamonn

    2016-01-01

    Olmesartan-induced enteropathy mimics celiac disease clinically and pathologically. As in celiac disease, the pathologic findings are villous atrophy and increased intraepithelial lymphocytes. Clinical presentation of olmesartan-induced enteropathy includes diarrhea, weight loss, and nausea. In contrast to celiac disease, tissue transglutaminase is not elevated and there is no response to a gluten-free diet. Including this entity in the differential diagnosis of sprue-like enteropathy is critical for its early diagnosis since replacing olmesartan with an alternative antihypertensive drug can simplify the diagnostic workup and provide both clinical and histologic improvement. PMID:28289500

  8. Injection-induced earthquakes.

    PubMed

    Ellsworth, William L

    2013-07-12

    Earthquakes in unusual locations have become an important topic of discussion in both North America and Europe, owing to the concern that industrial activity could cause damaging earthquakes. It has long been understood that earthquakes can be induced by impoundment of reservoirs, surface and underground mining, withdrawal of fluids and gas from the subsurface, and injection of fluids into underground formations. Injection-induced earthquakes have, in particular, become a focus of discussion as the application of hydraulic fracturing to tight shale formations is enabling the production of oil and gas from previously unproductive formations. Earthquakes can be induced as part of the process to stimulate the production from tight shale formations, or by disposal of wastewater associated with stimulation and production. Here, I review recent seismic activity that may be associated with industrial activity, with a focus on the disposal of wastewater by injection in deep wells; assess the scientific understanding of induced earthquakes; and discuss the key scientific challenges to be met for assessing this hazard.

  9. Shrouded inducer pump

    DOEpatents

    Meng, S.Y.

    1989-08-08

    An improvement in a pump is described including a shrouded inducer, the improvement comprising first and second sealing means which cooperate with a first vortex cell and a series of secondary vortex cells to remove any tangential velocity components from the recirculation flow. 3 figs.

  10. [Chemotherapy-induced alopecia].

    PubMed

    Spaëth, Dominique; Rosso, Nathalie; Clivot, Laetitia

    2006-11-30

    Chemotherapy-induced alopecia is frequent with most chemotherapy regimens; mechanisms, evolution and small prevention tools are described. Scalp cooling (helmets or continuous cooling systems) can avoid or diminish hair loss in selected chemotherapy regimens but tolerance can be fair and long harmlessness needs to be confirmed by prospective studies. Drug prevention is only in the first steps of research.

  11. Effects of Induced Astigmatism.

    ERIC Educational Resources Information Center

    Schubert, Delwyn G.; Walton, Howard N.

    1968-01-01

    The relationship of astigmatism to reading and the possible detrimental effects it might have on reading were investigated. The greatest incidence of astigmatism was for the with-the-rule type ranging from .50 to 1.00 diopter. This type of astigmatism was induced in 35 seniors from the Los Angeles College of Optometry by placing cylindrical lenses…

  12. Drug-induced uveitis

    PubMed Central

    2013-01-01

    A number of medications have been associated with uveitis. This review highlights both well-established and recently reported systemic, topical, intraocular, and vaccine-associated causes of drug-induced uveitis, and assigns a quantitative score to each medication based upon criteria originally described by Naranjo and associates. PMID:23522744

  13. Drug-induced hyperkalemia.

    PubMed

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

  14. Injection-induced earthquakes

    USGS Publications Warehouse

    Ellsworth, William L.

    2013-01-01

    Earthquakes in unusual locations have become an important topic of discussion in both North America and Europe, owing to the concern that industrial activity could cause damaging earthquakes. It has long been understood that earthquakes can be induced by impoundment of reservoirs, surface and underground mining, withdrawal of fluids and gas from the subsurface, and injection of fluids into underground formations. Injection-induced earthquakes have, in particular, become a focus of discussion as the application of hydraulic fracturing to tight shale formations is enabling the production of oil and gas from previously unproductive formations. Earthquakes can be induced as part of the process to stimulate the production from tight shale formations, or by disposal of wastewater associated with stimulation and production. Here, I review recent seismic activity that may be associated with industrial activity, with a focus on the disposal of wastewater by injection in deep wells; assess the scientific understanding of induced earthquakes; and discuss the key scientific challenges to be met for assessing this hazard.

  15. Geomagnetism and Induced Voltage

    ERIC Educational Resources Information Center

    Abdul-Razzaq, W.; Biller, R. D.

    2010-01-01

    Introductory physics laboratories have seen an influx of "conceptual integrated science" over time in their classrooms with elements of other sciences such as chemistry, biology, Earth science, and astronomy. We describe a laboratory to introduce this development, as it attracts attention to the voltage induced in the human brain as it…

  16. Shrouded inducer pump

    SciTech Connect

    Meng, Sen Y.

    1989-01-01

    An improvement in a pump including a shrouded inducer, the improvement comprising first and second sealing means 32,36 which cooperate with a first vortex cell 38 and a series of secondary vortex cells 40 to remove any tangential velocity components from the recirculation flow.

  17. Statin-induced Myopathy.

    PubMed

    Fitzgerald, Kara; Redmond, Elizabeth; Harbor, Cathryn

    2012-05-01

    Heart disease (HD) is the number one killer in the United States.(1) In 2006, the direct and indirect costs associated with cardiovascular disease in the United States were estimated at 400 billion dollars.(2) Statin therapy for cholesterol reduction is a mainstay intervention for cardiovascular disease (CVD) as reflected in atorvastatin's status as the number one prescribed medication in the United States.(3) Statin therapy, however, is also associated with side effects that signal mitochondrial distress. A commonly reported statin-induced symptom is myalgia, which is defined as muscle pain without an associated elevation of serum creatine kinase (CK). In clinical trials, the reports of myalgia vary from less than 1% to 25% of patients.(4) Myopathy is a general term defined as an abnormal condition or disease of muscle tissue. Myopathy includes myalgia, myositis (inflammation of muscle tissue associated with elevated CK) and the very serious condition rhabdomyolysis (extreme myositis). Histological findings in statin-induced myopathy demonstrate electron chain dysfunction making "mitochondrial myopathy" the more precise term.(5) Mitochondrial myopathy has been associated with statin-induced CoQ10 depletion.(5) Given the density of mitochondria in cardiomyocytes, and CoQ10's role in mitochondrial energy production, depletion has long been associated with increased risk for heart disease.(6-7) In the case below, mitochondrial-specific organic acids, serum CoQ10, vitamin D and clinical history all suggest statin-induced mitochondrial myopathy, despite normal serum CK.

  18. Bacteriocin Inducer Peptides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Novel peptides produced by bacteriocin-producing bacteria stimulate the production of bacteriocins in vitro. The producer bacteria are cultured in the presence of a novel inducer bacteria and a peptide having a carboxy terminal sequence of VKGLT in order to achieve an increase in bacteriocin produc...

  19. Induced Angular Momentum

    ERIC Educational Resources Information Center

    Parker, G. W.

    1978-01-01

    Discusses, classically and quantum mechanically, the angular momentum induced in the bound motion of an electron by an external magnetic field. Calculates the current density and its magnetic moment, and then uses two methods to solve the first-order perturbation theory equation for the required eigenfunction. (Author/GA)

  20. Topological induced gravity

    NASA Astrophysics Data System (ADS)

    Oda, Ichiro

    We propose a topological model of induced gravity (pregeometry) where both Newton’s coupling constant and the cosmological constant appear as integration constants in solving field equations. The matter sector of a scalar field is also considered, and by solving field equations it is shown that various types of cosmological solutions in the Friedmann-Robertson-Walker (FRW) universe can be obtained. A detailed analysis is given of the meaning of the BRST transformations, which make the induced gravity be a topological field theory, by means of the canonical quantization analysis, and the physical reason why such BRST transformations are needed in the present formalism is clarified. Finally, we propose a dynamical mechanism for fixing the Lagrange multiplier fields by following the Higgs mechanism. The present study clearly indicates that the induced gravity can be constructed at the classical level without recourse to quantum fluctuations of matter and suggests an interesting relationship between the induced gravity and the topological quantum-field theory (TQFT).

  1. Schedule-Induced Stereotypy.

    ERIC Educational Resources Information Center

    Emerson, Eric; Howard, Denise

    1992-01-01

    The phenomena of the induction and entrainment of adjunctive behaviors was investigated in 8 people (ages 5-51) with severe or profound mental retardation who exhibited stereotypic behaviors. Seven of the eight demonstrated evidence of schedule-induced stereotypic behavior, whereas five also showed evidence of the entrainment of these behaviors by…

  2. Warfarin-induced erythroderma.

    PubMed

    Rowe, Casey J; Robertson, Ivan; James, Daniel; McMeniman, Erin

    2015-02-01

    Erythroderma is a potentially serious and life-threatening skin disease with a number of possible aetiologies. Drug reactions are well-documented causes, with carbamazepine, penicillin and allopurinol being the most commonly implicated. This case describes a unique presentation of warfarin-induced erythroderma in a 78-year-old female patient.

  3. Friction induced rail vibrations

    NASA Astrophysics Data System (ADS)

    Kralov, Ivan; Sinapov, Petko; Nedelchev, Krasimir; Ignatov, Ignat

    2012-11-01

    A model of rail, considered as multiple supported beam, subjected on friction induced vibration is studied in this work using FEM. The model is presented as continuous system and the mass and elastic properties of a real object are taken into account. The friction forces are nonlinear functions of the relative velocity during slipping. The problem is solved using Matlab Simulink.

  4. Heparin-induced thrombocytopaenia.

    PubMed

    Gounden, Ronald; Blockman, Marc

    2008-01-01

    Heparin-induced thrombocytopaenia (HIT) is an acquired, transient prothrombotic disorder caused by heparin. The predominant problem is the creation of a prothrombotic milieu, accompanied by a fall in the platelet count. This explains the apparent paradox of thrombosis in the face of thrombocytopaenia and why non-heparin antithrombotic agents are integral to its management.

  5. Viral induced demyelination.

    PubMed

    Stohlman, S A; Hinton, D R

    2001-01-01

    Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell-cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is readily evident, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). Although of interest in their own right, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non-enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary result of axonal loss, in many examples of viral induced demyelination, myelin loss is primary and associated with axonal sparing. This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus-specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the

  6. [Steroid-induced osteoporosis].

    PubMed

    Perrot, Serge; Le Jeunne, Claire

    2012-04-01

    Bone-related steroid involvement is one of the most frequent complications of steroid treatment. Epidemiological data demonstrate that osteoporosis starts early during the treatment, predominantly involves trabecular bone and is correlated to dosage and treatment duration. Mechanisms and consequences of steroid bone involvement are related to osseous and extra-osseous mechanisms. In clinical practice, steroid-induced osteoporosis remains underdiagnosed and undertreated both in preventive and curative approaches. Recently, new molecules as teriparatide and zoledronic acid got indication for the treatment of steroid-induced osteoporosis. To guide treatment strategies, several recommendations are available: French, not updated recommendations since 2003 (Afssaps, 2003), European elaborated by the EULAR in 2007 and those of the ACR updated in 2010.

  7. Hypoxia-Inducible Hydrogels

    PubMed Central

    Park, Kyung Min; Gerecht, Sharon

    2014-01-01

    Oxygen is vital for the existence of all multicellular organisms, acting as a signaling molecule regulating cellular activities. Specifically, hypoxia, which occurs when the partial pressure of oxygen falls below 5%, plays a pivotal role during development, regeneration, and cancer. Here we report a novel hypoxia-inducible (HI) hydrogel composed of gelatin and ferulic acid that can form hydrogel networks via oxygen consumption in a laccase-mediated reaction. Oxygen levels and gradients within the hydrogels can be accurately controlled and precisely predicted. We demonstrate that HI hydrogels guide vascular morphogenesis in vitro via hypoxia-inducible factors activation of matrix metalloproteinases and promote rapid neovascularization from the host tissue during subcutaneous wound healing. The HI hydrogel is a new class of biomaterials that may prove useful in many applications, ranging from fundamental studies of developmental, regenerative and disease processes through the engineering of healthy and diseased tissue models towards the treatment of hypoxia-regulated disorders. PMID:24909742

  8. Current induced interlayer coupling

    NASA Astrophysics Data System (ADS)

    Levy, Peter M.; Heide, Carsten; Zhang, Shufeng; Fert, Albert

    2001-03-01

    It has recently been shown that a perpendicular current in a magnetically multilayered structures induces an unusual bilinear coupling between the magnetizations of the layers [1]. While this was demonstrated in the ballistic regime, transport is likely to be diffusive in the structures where this may be relevant to the role of currents in switching the magnetization of the layers. We have derived the current induced coupling by using the Boltzmann equation in terms of the parameters used to describe the giant magnetoresistance of magnetically layered structures, and thereby estimate the strength of this coupling. Work supported in part by DARPA and ONR. [1] C.Heide and R.J.Elliott, Europhys. Lett. 50, 271 (2000).

  9. Tulipalin A induced phytotoxicity.

    PubMed

    McCluskey, James; Bourgeois, Marie; Harbison, Raymond

    2014-04-01

    Tulipalin A induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to Alstroemeria and its cultivars.[1] The causative allergen is tulipalin A, a toxic glycoside named for the tulip bulbs from which it was first isolated.[2] The condition is characterized by fissured acropulpitis, often accompanied by hyperpigmentation, onychorrhexis, and paronychia. More of the volar surface may be affected in sensitized florists. Dermatitis and paronychia are extremely common conditions and diagnostic errors may occur. A thorough patient history, in conjunction with confirmatory patch testing with a bulb sliver and tuliposide A exposure, can prevent misdiagnosis. We report a case of Tulipalin A induced phytotoxicity misdiagnosed as an unresolved tinea manuum infection in a patient evaluated for occupational exposure.

  10. Tulipalin A induced phytotoxicity

    PubMed Central

    McCluskey, James; Bourgeois, Marie; Harbison, Raymond

    2014-01-01

    Tulipalin A induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to Alstroemeria and its cultivars.[1] The causative allergen is tulipalin A, a toxic glycoside named for the tulip bulbs from which it was first isolated.[2] The condition is characterized by fissured acropulpitis, often accompanied by hyperpigmentation, onychorrhexis, and paronychia. More of the volar surface may be affected in sensitized florists. Dermatitis and paronychia are extremely common conditions and diagnostic errors may occur. A thorough patient history, in conjunction with confirmatory patch testing with a bulb sliver and tuliposide A exposure, can prevent misdiagnosis. We report a case of Tulipalin A induced phytotoxicity misdiagnosed as an unresolved tinea manuum infection in a patient evaluated for occupational exposure. PMID:25024947

  11. Sepsis-induced Cardiomyopathy

    PubMed Central

    Romero-Bermejo, Francisco J; Ruiz-Bailen, Manuel; Gil-Cebrian, Julián; Huertos-Ranchal, María J

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

  12. Buckling-Induced Kirigami

    NASA Astrophysics Data System (ADS)

    Rafsanjani, Ahmad; Bertoldi, Katia

    2017-02-01

    We investigate the mechanical response of thin sheets perforated with a square array of mutually orthogonal cuts, which leaves a network of squares connected by small ligaments. Our combined analytical, experimental and numerical results indicate that under uniaxial tension the ligaments buckle out of plane, inducing the formation of 3D patterns whose morphology is controlled by the load direction. We also find that by largely stretching the buckled perforated sheets, plastic strains develop in the ligaments. This gives rise to the formation of kirigami sheets comprising periodic distribution of cuts and permanent folds. As such, the proposed buckling-induced pop-up strategy points to a simple route for manufacturing complex morphable structures out of flat perforated sheets.

  13. Buckling-Induced Kirigami.

    PubMed

    Rafsanjani, Ahmad; Bertoldi, Katia

    2017-02-24

    We investigate the mechanical response of thin sheets perforated with a square array of mutually orthogonal cuts, which leaves a network of squares connected by small ligaments. Our combined analytical, experimental and numerical results indicate that under uniaxial tension the ligaments buckle out of plane, inducing the formation of 3D patterns whose morphology is controlled by the load direction. We also find that by largely stretching the buckled perforated sheets, plastic strains develop in the ligaments. This gives rise to the formation of kirigami sheets comprising periodic distribution of cuts and permanent folds. As such, the proposed buckling-induced pop-up strategy points to a simple route for manufacturing complex morphable structures out of flat perforated sheets.

  14. Cocaine-Induced Vasculitis

    PubMed Central

    Berman, Mark; Paran, Daphna; Elkayam, Ori

    2016-01-01

    The use of cocaine continues to grow worldwide. One of the possible side-effects of cocaine is vasculitis. Two distinct vasculitic syndromes have been described due to cocaine. One is cocaine-induced midline destructive lesion, secondary to a direct vasoconstrictor effect of cocaine, inducing ischemic necrosis of the septal cartilage and perforation of the nasal septum, mimicking findings of granulomatosis with polyangiitis in the upper airways. The other is ANCA-associated vasculitis, attributed to the levamisole component that contaminates about 70% of the cocaine. This type of vasculitis may be myeloperoxidase (MPO) and proteinase 3 (PR3) positive, and its main manifestations are typical cutaneous findings, arthralgia, otolaryngologic involvement, and agranulocytosis. A high degree of suspicion and awareness is needed in order properly to diagnose and treat these patients. PMID:27824551

  15. Drug-induced hypokalaemia.

    PubMed

    Ben Salem, Chaker; Hmouda, Houssem; Bouraoui, Kamel

    2009-01-01

    Hypokalaemia (defined as a plasma potassium concentration<3.5 mEq/L) is a common electrolyte abnormality in clinical practice. Drugs are a common cause of either asymptomatic or symptomatic hypokalaemia. Drug-induced hypokalaemia is an important problem particularly in the elderly and in patients with cardiovascular, renal or hepatic disease. Hypokalaemia can complicate the use of the drug in the therapeutic concentration range, and can also be precipitated with overdose or conditions leading to drug intoxication. Because the etiologies of hypokalaemia are numerous, the diagnosis of drug-induced hypokalaemia may be overlooked. Physicians should always pay close attention to this common side effect. Evaluation and management of a hypokalaemic patient should include a careful review of medications history to determine if a drug capable of causing or aggravating this electrolyte abnormality is present.

  16. Radiation-induced schwannomas

    SciTech Connect

    Rubinstein, A.B.; Reichenthal, E.; Borohov, H.

    1989-06-01

    The histopathology and clinical course of three patients with schwannomas of the brain and high cervical cord after therapeutic irradiation for intracranial malignancy and for ringworm of the scalp are described. Earlier reports in the literature indicated that radiation of the scalp may induce tumors in the head and neck. It is therefore suggested that therapeutic irradiation in these instances was a causative factor in the genesis of these tumors.

  17. Polarization induced doped transistor

    SciTech Connect

    Xing, Huili; Jena, Debdeep; Nomoto, Kazuki; Song, Bo; Zhu, Mingda; Hu, Zongyang

    2016-06-07

    A nitride-based field effect transistor (FET) comprises a compositionally graded and polarization induced doped p-layer underlying at least one gate contact and a compositionally graded and doped n-channel underlying a source contact. The n-channel is converted from the p-layer to the n-channel by ion implantation, a buffer underlies the doped p-layer and the n-channel, and a drain underlies the buffer.

  18. Drug-induced diarrhoea.

    PubMed

    Chassany, O; Michaux, A; Bergmann, J F

    2000-01-01

    Diarrhoea is a relatively frequent adverse event, accounting for about 7% of all drug adverse effects. More than 700 drugs have been implicated in causing diarrhoea; those most frequently involved are antimicrobials, laxatives, magnesium-containing antacids, lactose- or sorbitol-containing products, nonsteroidal anti-inflammatory drugs, prostaglandins, colchicine, antineoplastics, antiarrhythmic drugs and cholinergic agents. Certain new drugs are likely to induce diarrhoea because of their pharmacodynamic properties; examples include anthraquinone-related agents, alpha-glucosidase inhibitors, lipase inhibitors and cholinesterase inhibitors. Antimicrobials are responsible for 25% of drug-induced diarrhoea. The disease spectrum of antimicrobial-associated diarrhoea ranges from benign diarrhoea to pseudomembranous colitis. Several pathophysiological mechanisms are involved in drug-induced diarrhoea: osmotic diarrhoea, secretory diarrhoea, shortened transit time, exudative diarrhoea and protein-losing enteropathy, and malabsorption or maldigestion of fat and carbohydrates. Often 2 or more mechanisms are present simultaneously. In clinical practice, 2 major types of diarrhoea are seen: acute diarrhoea, which usually appears during the first few days of treatment, and chronic diarrhoea, lasting more than 3 or 4 weeks and which can appear a long time after the start of drug therapy. Both can be severe and poorly tolerated. In a patient presenting with diarrhoea, the medical history is very important, especially the drug history, as it can suggest a diagnosis of drug-induced diarrhoea and thereby avoid multiple diagnostic tests. The clinical examination should cover severity criteria such as fever, rectal emission of blood and mucus, dehydration and bodyweight loss. Establishing a relationship between drug consumption and diarrhoea or colitis can be difficult when the time elapsed between the start of the drug and the onset of symptoms is long, sometimes up to several

  19. Arsenic-Induced Pancreatitis

    PubMed Central

    Connelly, Sean; Zancosky, Krysia; Farah, Katie

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide has brought about tremendous advancement in the treatment of acute promyelocytic myelogenous leukemia (APML). In most instances, the benefits of these treatments outweigh the risks associated with their respective safety profiles. Although acute pancreatitis is not commonly associated with arsenic toxicity, it should be considered as a possible side effect. We report a case of arsenic-induced pancreatitis in a patient with APML. PMID:22606427

  20. Ketamine-Induced Hallucinations

    PubMed Central

    Powers, A.R.; Gancsos, M.G.; Finn, E.S.; Morgan, P.T.; Corlett, P.R.

    2015-01-01

    Background Ketamine, the NMDA glutamate receptor antagonist drug, is increasingly employed as an experimental model of psychosis in healthy volunteers. At sub-anesthetic doses, it safely and reversibly causes delusion-like ideas, amotivation, and perceptual disruptions reminiscent of the aberrant salience experiences that characterize first-episode psychosis. However, auditory verbal hallucinations (AVHs), a hallmark symptom of schizophrenia, have not been reported consistently in healthy volunteers even at high doses of ketamine. Methods Here we present data from a set of healthy participants who received moderately dosed, placebo controlled ketamine infusions in the reduced stimulation environment of the magnetic resonance imaging scanner. We highlight the phenomenological experiences of three participants who experienced particularly vivid hallucinations. Results Participants in this series reported auditory verbal and musical hallucinations at a ketamine dose that does not induce auditory hallucination outside of the scanner. Discussion We interpret the observation of ketamine-induced AVHs in the context of the reduced perceptual environment of the magnetic resonance scanner, and offer an explanation grounded in predictive coding models of perception and psychosis: the brain fills in expected perceptual inputs and it does so more in situations of reduced perceptual input. The reduced perceptual input of the MRI scanner creates a mismatch between top-down perceptual expectations and the heightened bottom-up signals induced by ketamine; such circumstances induce aberrant percepts including musical and auditory verbal hallucinations. We suggest that these circumstances might represent a useful experimental model of AVHs and highlight the impact of ambient sensory stimuli on psychopathology. PMID:26361209

  1. Allopurinol induced erythroderma.

    PubMed

    Sharma, Geeta; Govil, Dinesh Chandra

    2013-01-01

    Allopurinol, a widely prescribed urate lowering agent is responsible for various adverse drug reactions, including erythroderma. A 45-year-old male patient was admitted with the complaints of fever, redness and scaling all over the body after 3-4 weeks of allopurinol treatment for asymptomatic hyperuricemia. Elevated liver enzymes were detected in his blood analysis. Skin biopsy was consistent with drug induced erythroderma. Allopurinol was stopped and steroids were started. Patient improved over a period of 2 weeks.

  2. Allergen-induced asthma

    PubMed Central

    Cockcroft, Donald W

    2014-01-01

    It was only in the late 19th century that specific allergens, pollen, animal antigens and, later, house dust mite, were identified to cause upper and lower airway disease. Early allergen challenge studies, crudely monitored before measurement of forced expiratory volume in 1 s became widespread in the 1950s, focused on the immediate effects but noted in passing prolonged and/or recurrent asthma symptoms. The late asthmatic response, recurrent bronchoconstriction after spontaneous resolution of the early responses occurring 3 h to 8 h or more postchallenge, has been identified and well characterized over the past 50 years. The associated allergen-induced airway hyper-responsiveness (1977) and allergen-induced airway inflammation (1985) indicate that these late sequelae are important in the mechanism of allergen-induced asthma. Allergens are now recognized to be the most important cause of asthma. A standardized allergen inhalation challenge model has been developed and is proving to be a valuable research tool in the investigation of asthma pathophysiology and of potential new pharmacological agents for the treatment of asthma. PMID:24791256

  3. Glycerol-induced hyperhydration

    NASA Technical Reports Server (NTRS)

    Riedesel, Marvin L.; Lyons, Timothy P.; Mcnamara, M. Colleen

    1991-01-01

    Maintenance of euhydration is essential for maximum work performance. Environments which induce hypohydration reduce plasma volume and cardiovascular performance progressively declines as does work capacity. Hyperhydration prior to exposure to dehydrating environments appears to be a potential countermeasure to the debilitating effects of hypohydration. The extravascular fluid space, being the largest fluid compartment in the body, is the most logical space by which significant hyperhydration can be accomplished. Volume and osmotic receptors in the vascular space result in physiological responses which counteract hyperhydration. Our hypothesis is that glycerol-induced hyperhydration (GIH) can accomplish extravascular fluid expansion because of the high solubility of glycerol in lipid and aqueous media. A hypertonic solution of glycerol is rapidly absorbed from the gastrointestinal tract, results in mild increases in plasma osmolality and is distributed to 65 percent of the body mass. A large volume of water ingested within minutes after glycerol intake results in increased total body water because of the osmotic action and distribution of glycerol. The resulting expanded extravascular fluid space can act as a reservoir to maintain plasma volume during exposure to dehydrating environments. The fluid shifts associated with exposure to microgravity result in increased urine production and is another example of an environment which induces hypohydration. Our goal is to demonstrate that GIH will facilitate maintenance of euhydration and cardiovascular performance during space flight and upon return to a 1 g environment.

  4. Induced QCD I: theory

    NASA Astrophysics Data System (ADS)

    Brandt, Bastian B.; Lohmayer, Robert; Wettig, Tilo

    2016-11-01

    We explore an alternative discretization of continuum SU( N c ) Yang-Mills theory on a Euclidean spacetime lattice, originally introduced by Budzcies and Zirnbauer. In this discretization the self-interactions of the gauge field are induced by a path integral over N b auxiliary boson fields, which are coupled linearly to the gauge field. The main progress compared to earlier approaches is that N b can be as small as N c . In the present paper we (i) extend the proof that the continuum limit of the new discretization reproduces Yang-Mills theory in two dimensions from gauge group U( N c ) to SU( N c ), (ii) derive refined bounds on N b for non-integer values, and (iii) perform a perturbative calculation to match the bare parameter of the induced gauge theory to the standard lattice coupling. In follow-up papers we will present numerical evidence in support of the conjecture that the induced gauge theory reproduces Yang-Mills theory also in three and four dimensions, and explore the possibility to integrate out the gauge fields to arrive at a dual formulation of lattice QCD.

  5. Ethanol-induced analgesia

    SciTech Connect

    Pohorecky, L.A.; Shah, P.

    1987-09-07

    The effect of ethanol (ET) on nociceptive sensitivity was evaluated using a new tail deflection response (TDR) method. The IP injection of ET (0.5 - 1.5 g/kg) produced raid dose-dependent analgesia. Near maximal effect (97% decrease in TDR) was produced with the 1.5 g/kg dose of ET ten minutes after injection. At ninety minutes post-injection there was still significant analgesia. Depression of ET-induced nociceptive sensitivity was partially reversed by a 1 mg/kg dose of naloxone. On the other hand, morphine (0.5 or 5.0 mg/kg IP) did not modify ET-induced analgesia, while 3.0 minutes of cold water swim (known to produce non-opioid mediated analgesia) potentiated ET-induced analgesic effect. The 0.5 g/kg dose of ET by itself did not depress motor activity in an open field test, but prevented partially the depression in motor activity produced by cold water swim (CWS). Thus, the potentiation by ET of the depression of the TDR produced by CWS cannot be ascribed to the depressant effects of ET on motor activity. 21 references, 4 figures, 1 table.

  6. Study of cavitating inducer instabilities

    NASA Technical Reports Server (NTRS)

    Young, W. E.; Murphy, R.; Reddecliff, J. M.

    1972-01-01

    An analytic and experimental investigation into the causes and mechanisms of cavitating inducer instabilities was conducted. Hydrofoil cascade tests were performed, during which cavity sizes were measured. The measured data were used, along with inducer data and potential flow predictions, to refine an analysis for the prediction of inducer blade suction surface cavitation cavity volume. Cavity volume predictions were incorporated into a linearized system model, and instability predictions for an inducer water test loop were generated. Inducer tests were conducted and instability predictions correlated favorably with measured instability data.

  7. Radiation Induced Genomic Instability

    SciTech Connect

    Morgan, William F.

    2011-03-01

    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a “mutator phenotype” (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target – the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend

  8. Polycation induced actin bundles.

    PubMed

    Muhlrad, Andras; Grintsevich, Elena E; Reisler, Emil

    2011-04-01

    Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon the addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations and the neutralization of repulsive interactions of negative charges on actin. The attractive forces between the filaments are strong, as shown by the low (in nanomolar range) critical concentration of their bundling at low ionic strength. These bundles are sensitive to ionic strength and disassemble partially in 100 mM NaCl, but both the dissociation and ionic strength sensitivity can be countered by higher polycation concentrations. Cys374 residues of actin monomers residing on neighboring filaments in the bundles can be cross-linked by the short span (5.4Å) MTS-1 (1,1-methanedyl bismethanethiosulfonate) cross-linker, which indicates a tight packing of filaments in the bundles. The interfilament cross-links, which connect monomers located on oppositely oriented filaments, prevent disassembly of bundles at high ionic strength. Cofilin and the polysaccharide polyanion heparin disassemble lysozyme induced actin bundles more effectively than the polylysine-induced bundles. The actin-lysozyme bundles are pathologically significant as both proteins are found in the pulmonary airways of cystic fibrosis patients. Their bundles contribute to the formation of viscous mucus, which is the main cause of breathing difficulties and eventual death in this disorder.

  9. Method for inducing hypothermia

    DOEpatents

    Becker, Lance B.; Hoek, Terry Vanden; Kasza, Kenneth E.

    2003-04-15

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  10. Method for inducing hypothermia

    DOEpatents

    Becker, Lance B.; Hoek, Terry Vanden; Kasza, Kenneth E.

    2005-11-08

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  11. Isoniazid-induced pellagra.

    PubMed

    Bilgili, Serap Gunes; Karadag, Ayse Serap; Calka, Omer; Altun, Faruk

    2011-12-01

    Pellagra is characterized by dermatitis, diarrhea, dementia and eventually death occurring as a result of niacin or its precursor tryptophan deficiency. Although pellagra is a well-known complication of isoniazid (INH) therapy, the clinical diagnosis may be missed or delayed that may cause life-threatening consequences. Due to the diversity of pellagra-related signs and symptoms, the diagnosis can be made with an appropriate index of suspicion. We report a 7-year-old boy presenting with INH-induced pellagra that resolved after the administration of the niacin therapy.

  12. Trastuzumab-induced cardiomyopathy.

    PubMed

    Guglin, Maya; Cutro, Raymond; Mishkin, Joseph D

    2008-06-01

    Trastuzumab is a recombinant humanized monoclonal antibody used for the treatment of advanced breast cancer. It improves survival and increases response to chemotherapy. The major side effect of trastuzumab is cardiotoxicity manifesting as a reduction in left ventricular systolic function, either asymptomatic or with signs and symptoms of heart failure. Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab. The objective of this review is to summarize facts about trastuzumab-induced cardiotoxicity and to highlight the areas of future investigations. We searched PubMed for trials involving trastuzumab used as an adjuvant therapy for breast cancer, including the metastatic breast cancer setting, and focused on cardiotoxicity.

  13. Bupropion-induced somnambulism.

    PubMed

    Khazaal, Yasser; Krenz, Sonia; Zullino, Daniele Fabio

    2003-09-01

    Whereas there are some case reports of bupropion-induced vivid dreaming and nightmares, until now it has not been associated with somnambulism. A case is reported of a patient treated with bupropion as a smoking cessation medication, who developed somnambulism during nicotine withdrawal. Furthermore, the sleepwalking episodes were associated with eating behaviour. Amnesia was reported for all episodes. As, on one hand,bupropion is a noradrenergic and dopaminergic drug and nicotine withdrawal, on the other hand, is associated with alterations in monoaminergic functions, an interaction at the level of these neurotransmitters is suggested as the underlying mechanism.

  14. [Neuroleptic induced deficit syndrome].

    PubMed

    Szafrański, T

    1995-01-01

    Increasing interest in subjective aspects of therapy and rehabilitation focused the attention of psychiatrists, psychologists and psychopharmacologists on the mental side effects of neuroleptics. For the drug-related impairment of affective, cognitive and social function the name of neuroleptic-induced deficit syndrome (NIDS) is proposed. Patients with NIDS appear to be indifferent to the environmental stimuli, retarded and apathetic. They complain of feeling drugged and drowsy, weird, they suffer from lack of motivation, feel like "zombies". The paper presents description of NIDS and its differentiation from negative and depressive symptoms in schizophrenia and subjective perceiving of extrapyramidal syndromes.

  15. Drug-induced gynecomastia.

    PubMed

    Eckman, Ari; Dobs, Adrian

    2008-11-01

    Gynecomastia is caused by drugs in 10 - 25% of all cases. The pathophysiologic mechanism for some drugs includes exogenous estrogens exposure, medications that cause hypogonadism, anti-androgenic effects and hyperprolactinemia. This manuscript reviews common examples of drug-induced gynecomastia, discussing the mechanisms and possible treatments. Discontinuing the medication is always the best choice; however, if this is not possible, then testosterone replacement therapy may be needed for hypogonadism. When a man is euogonadal, a trial of the anti-estrogen, tamoxifen or an aromatase inhibitor may be an option.

  16. Inducing Pluripotency in Cattle.

    PubMed

    Malaver-Ortega, Luis F; Taheri-Ghahfarokhi, Amir; Sumer, Huseyin

    2015-01-01

    Nuclear reprogramming technologies in general and induced pluripotent stem cells (iPSCs) in particular have opened the door to a vast number of practical applications in regenerative medicine and biotechnology. It also represents a possible alternative to the still evasive achievement of embryonic stem cells (ESCs) isolation from refractory species such as Bos. taurus. Herein, we described a protocol for bovine iPSCs (biPSCs) generation and characterization. The protocol is based on the overexpression of the exogenous transcription factors NANOG, OCT4, SOX2, KLF4 and c-MYC, using a pantropic retroviral system.

  17. 5-fluorouracil induced pericarditis.

    PubMed

    Killu, Ammar; Madhavan, Malini; Prasad, Kavita; Prasad, Abhiram

    2011-04-15

    Cardiac toxicity is an infrequent, but potentially serious side effect of 5-fluorouracil (5-FU). The reported incidence of 5-FU-induced cardiotoxicity is approximately 3%, although estimates vary from 1.2% to 18%. Cardiac death occurs in less than 1%. The prompt recognition of cardiac toxicity demands a thorough understanding of the myriad of potential cardiac manifestations and a high index of suspicion. The most common presentation is angina pectoris while other manifestations, namely myocardial infarction, left ventricular dysfunction, arrhythmias and sudden death have been recognised. The authors report an unusual case of myopericarditis masquerading as myocardial infarction.

  18. Method for inducing hypothermia

    SciTech Connect

    Becker, Lance B.; Hoek, Terry Vanden; Kasza, Kenneth E.

    2008-09-09

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  19. Antacid-induced osteomalacia.

    PubMed

    Boutsen, Y; Devogelaer, J P; Malghem, J; Noel, H; Nagant de Deuxchaisnes, C

    1996-01-01

    The case of a 49-year-old woman suffering from generalized skeletal pain and multiple fractures accompanied by severe hypophosphataemia and low urinary phosphorus excretion is reported. She had been taking large amounts of antacids containing aluminum hydroxide for many years. A diagnosis of antacid-induced osteomalacia was made. It was confirmed by biological work-up, radiographs and bone biopsy. A dramatic biological, osteodensitometric, and clinical improvement was achieved by withdrawal of antacids and phosphorus administration. The literature concerning this unusual condition has been reviewed.

  20. Drug-induced lupus.

    PubMed

    Rubin, Robert L

    2005-04-15

    Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.

  1. [Exercise-induced anaphylaxis].

    PubMed

    Gani, Federica; Selvaggi, Lucia; Roagna, Davide

    2008-01-01

    Exercise-induced anaphylaxis (EIA) was defined for the first time in 1980. EIA is associated with different kind of exercise, although jogging is the most frequently reported. The clinical manifestations progress from itching, erythema and urticaria to some combination of cutaneous angioedema, gastrointestinal and laryngeal symptoms and signs of angioedema and vascular collapse. Mast cell participation in the pathogenesis of this syndrome has been proved by the finding of an elevated serum histamine level during experimentally-induced attacks and by cutaneous degranulation of mast cells with elevated serum tryptase after attacks. As predisposing factors of EIA, a specific or even aspecific sensitivity to food has been reported and such cases are called "food-dependent EIA". Many foods are implicated but particularly wheat, vegetables, crustacean. Another precipitating factor includes drugs intake (non steroidal anti-inflammatory drugs), climate variations and menstrual cycle factors. Treatment of an attack should include all the manoeuvres efficacious in the management of conventional anaphylactic syndrome, including the administration of epinephrine and antihistamines. Prevention of the attacks may be achieved with the interruption of the exercise at the appearance of the first premonitory symptoms. To prevent the onset of EIA it is also suitable to delay the exercise practice after at least 4-6 hours from the swallowing of food.

  2. Interferon induced thyroiditis.

    PubMed

    Tomer, Yaron; Menconi, Francesca

    2009-12-01

    Interferon-alpha (IFNalpha) is used for the treatment of various disorders, most notable chronic hepatitis C virus (HCV) infection. One of the commonest side effects of IFNalpha therapy is thyroiditis, with up to 40% of HCV patients on IFNalpha developing clinical or subclinical disease. In some cases interferon induced thyroiditis (IIT) may result in severe symptomatology necessitating discontinuation of therapy. IIT can manifest as clinical autoimmune thyroiditis, presenting with symptoms of classical Hashimoto's thyroiditis or Graves' disease, or as non-autoimmune thyroiditis. Non-autoimmune thyroiditis can manifest as destructive thyroiditis, with early thyrotoxicosis and later hypothyroidism, or as non-autoimmune hypothyroidism. While the epidemiology and clinical presentation of IIT have been well characterized the mechanisms causing IIT are still poorly understood. It is likely that the hepatitis C virus (HCV) itself plays a role in the disease, as the association between HCV infection and thyroiditis is well established. It is believed that IFNalpha induces thyroiditis by both immune stimulatory effects and by direct effects on the thyroid. Early detection and therapy of this condition are important in order to avoid complications of thyroid disease such as cardiac arrhythmias.

  3. [Gluten induced diseases].

    PubMed

    Frič, P; Zavoral, M; Dvořáková, T

    2013-05-01

    The introduction of cereals in human nutrition 10 000 years ago caused the occurrence of gluten induced diseases. This protein complex is involved in pathogenesis of wheat allergy, celiac disease, and gluten sensitivity. Wheat allergy and celiac disease are mediated by the system of adaptive immunity. Gluten sensitivity is a recently defined entity induced by innate immune mechanisms. These subjects present various intestinal and particularly extraintestinal symptoms. The differences between celiac disease and gluten intolerance include permeability of the intestinal mucosal barrier, histology of duodenal biopsy, and mucosal gene expression. The symptoms of gluten sensitivity may also have another genetic background of food intolerance independent of the HLADQ2, - DQ8 system and tissue transglutaminase (eg. in some psychiatric disorders). At present, there is no specific bio-marker of gluten sensitivity. The diagnosis is possible only by exclusion of other causes of symptoms and improvement on a glutenfree diet applied in a doubleblind placebo controlled manner with optional sequence of both stages to exclude the placebo effect due to nutritional intervention.

  4. Cholesterol depletion induces autophagy

    SciTech Connect

    Cheng, Jinglei; Ohsaki, Yuki; Tauchi-Sato, Kumi; Fujita, Akikazu; Fujimoto, Toyoshi . E-mail: tfujimot@med.nagoya-u.ac.jp

    2006-12-08

    Autophagy is a mechanism to digest cells' own components, and its importance in many physiological and pathological processes is being recognized. But the molecular mechanism that regulates autophagy is not understood in detail. In the present study, we found that cholesterol depletion induces macroautophagy. The cellular cholesterol in human fibroblasts was depleted either acutely using 5 mM methyl-{beta}-cyclodextrin or 10-20 {mu}g/ml nystatin for 1 h, or metabolically by 20 {mu}M mevastatin and 200 {mu}M mevalonolactone along with 10% lipoprotein-deficient serum for 2-3 days. By any of these protocols, marked increase of LC3-II was detected by immunoblotting and by immunofluorescence microscopy, and the increase was more extensive than that caused by amino acid starvation, i.e., incubation in Hanks' solution for several hours. The induction of autophagic vacuoles by cholesterol depletion was also observed in other cell types, and the LC3-positive membranes were often seen as long tubules, >50 {mu}m in length. The increase of LC3-II by methyl-{beta}-cyclodextrin was suppressed by phosphatidylinositol 3-kinase inhibitors and was accompanied by dephosphorylation of mammalian target of rapamycin. By electron microscopy, autophagic vacuoles induced by cholesterol depletion were indistinguishable from those seen after amino acid starvation. These results demonstrate that a decrease in cholesterol activates autophagy by a phosphatidylinositol 3-kinase-dependent mechanism.

  5. Statin-induced myopathies.

    PubMed

    Tomaszewski, Michał; Stępień, Karolina M; Tomaszewska, Joanna; Czuczwar, Stanisław J

    2011-01-01

    Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medications. The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis. Clinical trials commonly define statin toxicity as myalgia or muscle weakness with creatine kinase (CK) levels greater than 10 times the normal upper limit. Rhabdomyolysis is the most severe adverse effect of statins, which may result in acute renal failure, disseminated intravascular coagulation and death. The exact pathophysiology of statin-induced myopathy is not fully known. Multiple pathophysiological mechanisms may contribute to statin myotoxicity. This review focuses on a number of them. The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk. Currently, the only effective treatment of statin-induced myopathy is the discontinuation of statin use in patients affected by muscle aches, pains and elevated CK levels.

  6. Drug-induced exanthems.

    PubMed

    Yawalkar, Nikhil

    2005-04-15

    Cutaneous adverse reactions to drugs can comprise a broad spectrum of clinical and histopathological features. Recent evidence from immunohistological and functional studies of drug-reactive T cells suggest that distinct T-cell functions may be responsible for this broad spectrum of different clinical reactions. Maculopapular exanthems represent the most commonly encountered cutaneous drug eruption. Previous studies on maculopapular exanthems indicate that drug-specific CD4+ T cells expressing cytotoxic granule proteins such as perforin and granzyme B are critically involved in killing activated keratinocytes. These cells are particularly found at the dermo-epidermal junction and may contribute to the generation of vacuolar alteration and destruction of basal keratinocytes, which are typical found in drug-induced maculopapular exanthems. In contrast to maculopapular exanthems, the preferential activation of drug-specific cytotoxic CD8+ T cells may lead to more severe reactions like bullous drug eruptions. Furthermore, activation of drug-specific T with distinct cytokine and chemokines profiles may also explain the different clinical features of drug-induced exanthems. IL-5 and eotaxin are upregulated in maculopapular exanthems and explain the eosinophilia often found in these reactions.

  7. Role of brain norepinephrine in the behavioral response to stress.

    PubMed

    Morilak, David A; Barrera, Gabe; Echevarria, David J; Garcia, April S; Hernandez, Angelica; Ma, Shuaike; Petre, Corina O

    2005-12-01

    The brain noradrenergic system is activated by acute stress. The post-synaptic effects of norepinephrine (NE), exerted at a cellular or neural circuit level, have been described as modulatory in nature, as NE facilitates responses evoked in target cells by both excitatory and inhibitory afferent input. Over the past few years, we have undertaken a series of studies to understand how these cellular modulatory effects of NE, elicited by acute stress, might translate into modulation of the behavioral-affective components of the whole-animal response to stress. Using microdialysis, we have demonstrated that acute immobilization stress activates NE release in a number of stress-related limbic forebrain target regions, such as the central and medial amygdala, lateral bed nucleus of the stria terminalis, medial prefrontal cortex, and lateral septum. Using microinjections of adrenergic antagonist drugs directly into these regions, we have shown that this stress-induced release of NE facilitates a number of anxiety-like behavioral responses that are mediated in these regions, including stress-induced reduction of open-arm exploration on the elevated plus-maze, stress-induced reduction of social interaction behavior, and activation of defensive burying behavior by contact with an electrified probe. Dysregulation of the brain noradrenergic system may be a factor in determining vulnerability to stress-related pathology, or in the interaction of genetic vulnerability and environmental sensitization. Compared to outbred Sprague-Dawley rats, we have shown that the modulatory effect of NE is deficient in Wistar-Kyoto rats, which also exhibit attenuated behavioral reactivity to acute stress, as well as increased vulnerability to stress-induced gastric ulcers and exaggerated activation of the hypothalamic-pituitary-adrenal (HPA) stress axis. Further, repeated exposure to mild intermittent cold stress resulted in a much greater sensitization of both the brain noradrenergic system and

  8. Induced Seismicity Monitoring System

    NASA Astrophysics Data System (ADS)

    Taylor, S. R.; Jarpe, S.; Harben, P.

    2014-12-01

    There are many seismological aspects associated with monitoring of permanent storage of carbon dioxide (CO2) in geologic formations. Many of these include monitoring underground gas migration through detailed tomographic studies of rock properties, integrity of the cap rock and micro seismicity with time. These types of studies require expensive deployments of surface and borehole sensors in the vicinity of the CO2 injection wells. Another problem that may exist in CO2 sequestration fields is the potential for damaging induced seismicity associated with fluid injection into the geologic reservoir. Seismic hazard monitoring in CO2 sequestration fields requires a seismic network over a spatially larger region possibly having stations in remote settings. Expensive observatory-grade seismic systems are not necessary for seismic hazard deployments or small-scale tomographic studies. Hazard monitoring requires accurate location of induced seismicity to magnitude levels only slightly less than that which can be felt at the surface (e.g. magnitude 1), and the frequencies of interest for tomographic analysis are ~1 Hz and greater. We have developed a seismo/acoustic smart sensor system that can achieve the goals necessary for induced seismicity monitoring in CO2 sequestration fields. The unit is inexpensive, lightweight, easy to deploy, can operate remotely under harsh conditions and features 9 channels of recording (currently 3C 4.5 Hz geophone, MEMS accelerometer and microphone). An on-board processor allows for satellite transmission of parameter data to a processing center. Continuous or event-detected data is kept on two removable flash SD cards of up to 64+ Gbytes each. If available, data can be transmitted via cell phone modem or picked up via site visits. Low-power consumption allows for autonomous operation using only a 10 watt solar panel and a gel-cell battery. The system has been successfully tested for long-term (> 6 months) remote operations over a wide range

  9. Peripherally induced oromandibular dystonia

    PubMed Central

    Sankhla, C.; Lai, E.; Jankovic, J.

    1998-01-01

    OBJECTIVES—Oromandibular dystonia (OMD) is a focal dystonia manifested by involuntary muscle contractions producing repetitive, patterned mouth, jaw, and tongue movements. Dystonia is usually idiopathic (primary), but in some cases it follows peripheral injury. Peripherally induced cervical and limb dystonia is well recognised, and the aim of this study was to characterise peripherally induced OMD.
METHODS—The following inclusion criteria were used for peripherally induced OMD: (1) the onset of the dystonia was within a few days or months (up to 1 year) after the injury; (2) the trauma was well documented by the patient's history or a review of their medical and dental records; and (3) the onset of dystonia was anatomically related to the site of injury (facial and oral).
RESULTS—Twenty seven patients were identified in the database with OMD, temporally and anatomically related to prior injury or surgery. No additional precipitant other than trauma could be detected. None of the patients had any litigation pending. The mean age at onset was 50.11 (SD 14.15) (range 23-74) years and there was a 2:1 female preponderance. Mean latency between the initial trauma and the onset of OMD was 65 days (range 1 day-1 year). Ten (37%) patients had some evidence of predisposing factors such as family history of movement disorders, prior exposure to neuroleptic drugs, and associated dystonia affecting other regions or essential tremor. When compared with 21 patients with primary OMD, there was no difference for age at onset, female preponderance, and phenomenology. The frequency of dystonic writer's cramp, spasmodic dysphonia, bruxism, essential tremor, and family history of movement disorder, however, was lower in the post-traumatic group (p<0.05). In both groups the response to botulinum toxin treatment was superior to medical therapy (p<0.005). Surgical intervention for temporomandibular disorders was more frequent in the post-traumatic group and was associated with

  10. Circuits Regulating Pleasure and Happiness: The Evolution of the Amygdalar-Hippocampal-Habenular Connectivity in Vertebrates

    PubMed Central

    Loonen, Anton J. M.; Ivanova, Svetlana A.

    2016-01-01

    Appetitive-searching (reward-seeking) and distress-avoiding (misery-fleeing) behavior are essential for all free moving animals to stay alive and to have offspring. Therefore, even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must have been capable of generating these behaviors. The current article describes the evolution of the forebrain with special reference to the development of the misery-fleeing system. Although, the earliest vertebrate ancestor already possessed a dorsal pallium, which corresponds to the human neocortex, the structure and function of the neocortex was acquired quite recently within the mammalian evolutionary line. Up to, and including, amphibians, the dorsal pallium can be considered to be an extension of the medial pallium, which later develops into the hippocampus. The ventral and lateral pallium largely go up into the corticoid part of the amygdala. The striatopallidum of these early vertebrates becomes extended amygdala, consisting of centromedial amygdala (striatum) connected with the bed nucleus of the stria terminalis (pallidum). This amygdaloid system gives output to hypothalamus and brainstem, but also a connection with the cerebral cortex exists, which in part was created after the development of the more recent cerebral neocortex. Apart from bidirectional connectivity with the hippocampal complex, this route can also be considered to be an output channel as the fornix connects the hippocampus with the medial septum, which is the most important input structure of the medial habenula. The medial habenula regulates the activity of midbrain structures adjusting the intensity of the misery-fleeing response. Within the bed nucleus of the stria terminalis the human homolog of the ancient lateral habenula-projecting globus pallidus may exist; this structure is important for the evaluation of efficacy of the reward-seeking response. The described organization offers a framework for the

  11. Sexual dimorphism in the vomeronasal pathway and sex differences in reproductive behaviors.

    PubMed

    Segovia, S; Guillamón, A

    1993-01-01

    Several years ago we hypothesized that the vomeronasal system (VNS), a complex neural network involved in the control of reproductive behavior, might be sexually dimorphic. This hypothesis sprung from several facts; (a) the existence of steroid receptors in the VNS; (b) sexual dimorphism was already described in some structures that receive vomeronasal input, such as the medial preoptic area, the ventromedial hypothalamic nucleus, the ventral region of the premammillary nucleus and the medial amygdaloid nucleus; and (c) the vomeronasal organ, which is the receptor organ of the VNS, was also sexually dimorphic. After that point, the accessory olfactory bulb (AOB), the bed nucleus of the accessory olfactory tract (BAOT) and the bed nucleus of the stria terminalis were found to be sexually dimorphic. The aim of the present review is to show the experimental facts that confirm our earlier hypothesis and, consequently, to present the existence of a sexually dimorphic multisynaptic pathway for the first time in mammals. Sexual dimorphism in the VNS might provide a comprehensive approach to understanding the neural bases of sexually dimorphic reproductive behavior and it is suggested here that the greater number of neurons which male rats present in relation to females in most VNS structures might contribute to the inhibition of the expression of feminine copulatory behavior (lordosis) and maternal behavior in males. In addition, the mechanisms that control the development of sexual dimorphism in the VNS are discussed. The discussion takes into account the two patterns of sexual dimorphism found in the rat brain. Estrogens seem to promote the development of sexual dimorphism in both male and female rats. However, an inhibitory role of androgens might be necessary to hypothesize when males or females present a lower number of neurons and/or volume than the opposite sex. There are experimental data supporting this hypothesis in the female, since dihydrotestosterone seems to

  12. Drug-Induced Hematologic Syndromes

    PubMed Central

    Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

    2009-01-01

    Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

  13. Induced seismicity. Final report

    SciTech Connect

    Segall, P.

    1997-09-18

    The objective of this project has been to develop a fundamental understanding of seismicity associated with energy production. Earthquakes are known to be associated with oil, gas, and geothermal energy production. The intent is to develop physical models that predict when seismicity is likely to occur, and to determine to what extent these earthquakes can be used to infer conditions within energy reservoirs. Early work focused on earthquakes induced by oil and gas extraction. Just completed research has addressed earthquakes within geothermal fields, such as The Geysers in northern California, as well as the interactions of dilatancy, friction, and shear heating, on the generation of earthquakes. The former has involved modeling thermo- and poro-elastic effects of geothermal production and water injection. Global Positioning System (GPS) receivers are used to measure deformation associated with geothermal activity, and these measurements along with seismic data are used to test and constrain thermo-mechanical models.

  14. [Tachycardia-induced cardiomyopathy].

    PubMed

    Povolný, Jan

    2015-01-01

    Cardiomyopathy is a heterogeneous group of diseases of heart muscle accompanied with impaired cardiac function. Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia leading to dilatation and systolic dysfunction with clinical manifestation of heart failure. This state is reversible after normalization of heart rate. The diagnosis is usually made retrospectively after normalization of heart rate and recovery of left ventricular function (LVF). More than 100 years after the first documented case (described in 1913 in a young patient with atrial fibrillation and symptoms of heart failure [25]) is still limited knowledge of pathophysiological mechanisms. The most common arrhythmias responsible for the TIC include atrial fibrillation [1,2], atrial flutter [3], incessant supraventricular tachycardia [4], ventricular tachycardia (VT) [5] and frequent ventricular extrasystoles (VES) [6]. TIC detection and therapeutic intervention is crucial considering potential reversibility of tachycardia. Current options of treatment involve drug therapy and surgical or catheter ablation.

  15. Radiation-Induced Bioradicals

    NASA Astrophysics Data System (ADS)

    Lahorte, Philippe; Mondelaers, Wim

    This chapter represents the second part of a review in which the production and application of radiation-induced radicals in biological matter are discussed. In part one the general aspects of the four stages (physical, physicochemical, chemical and biological) of interaction of radiation with matter in general and biological matter in particular, were discussed. Here an overview is presented of modem technologies and theoretical methods available for studying these radiation effects. The relevance is highlighted of electron paramagnetic resonance spectroscopy and quantum chemical calculations with respect to obtaining structural information on bioradicals, and a survey is given of the research studies in this field. We also discuss some basic aspects of modem accelerator technologies which can be used for creating radicals and we conclude with an overview of applications of radiation processing in biology and related fields such as biomedical and environmental engineering, food technology, medicine and pharmacy.

  16. [Cannabis-induced disorders].

    PubMed

    Soyka, M; Preuss, U; Hoch, E

    2017-03-01

    Use and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies.

  17. Catatonia induced by levetiracetam.

    PubMed

    Chouinard, Marie-Josée; Nguyen, Dang-Khoa; Clément, Jean-François; Bruneau, Marie-Andrée

    2006-02-01

    Levetiracetam (Keppra) is a novel antiepileptic drug approved as adjunctive treatment for adults with partial onset seizures. Although the drug is generally well tolerated, behavioral side effects have been reported in variable frequency. Most behavioral problems are mild in nature (agitation, hostility, anxiety, emotional lability, apathy, depression) and quickly resolve with discontinuation of medication. However, serious psychiatric adverse events may also occur with rare cases of psychosis and suicidal behavior. We report here the case of a 43-year-old woman who developed symptoms compatible with catatonia after being exposed to levetiracetam for the treatment of epilepsy. To our knowledge, it is the first reported case of catatonia induced by levetiracetam. We review the difficulties that may be encountered in the differential diagnosis of medical catatonia.

  18. Gadolinium-Induced Fibrosis.

    PubMed

    Todd, Derrick J; Kay, Jonathan

    2016-01-01

    Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

  19. [Designer drug induced psychosis].

    PubMed

    Fullajtar, Mate; Ferencz, Csaba

    2012-06-01

    3,4-methylene-dioxy-pyrovalerone (MDPV) is a popular designer drug in Hungary, known as MP4. We present a case of a 34-year-old man, whose first psychotic episode was observed in the presence of MP4 use. The paranoid ideas of reference and the dereistic thinking could be the consequence of drug-induced psychosis. Within 24 hours after the intoxication was over delirium set in. The patient's history included only the use of MP4, use of other kinds of drugs was negated. The drug tests were negative, amphetamine derivates were not detectable in the urine sample. It is most likely that the MP4 pill contained an amount of MDPV less than detectable. In conclusion we suggest that the clinical picture could be the consequence of regular MDPV use.

  20. Laser-induced bioluminescence

    SciTech Connect

    Hickman, G.D.; Lynch, R.V. III

    1981-01-01

    A project has been initiated to determine the feasibility of developing a complete airborne remote sensing system for rapidly mapping high concentration patches of bioluminescent organisms in the world's oceans. Conceptually, this system would be composed of a laser illuminator to induce bioluminescence and a low light level image intensifier for detection of light. Initial laboratory measurements consisted of using a 2-J flash lamp pulsed optical dye laser to excite bioluminescence in the marine dinoflagellate Pyrocustis lunula at ambient temperature using Rhodamine 6G as the lasing dye (585 nm) and a laser pulse width of 1 microsec. After a latency period of 15-20 msec, the bioluminescence maximum occurred in the blue (480 nm is the wavelength maximum for most dinoflagellate bioluminescence) with the peaking occurring approximately 65 msec after the laser pulse. Planned experiments will investigate the effect of different excitation wavelengths and energies at various temperatures and salinities of the cultures.

  1. Radiation Induced Oral Mucositis

    PubMed Central

    PS, Satheesh Kumar; Balan, Anita; Sankar, Arun; Bose, Tinky

    2009-01-01

    Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene PMID:20668585

  2. [Drug-induced asterixis].

    PubMed

    Rittmannsberger, H; Leblhuber, F

    1994-04-22

    A 54-year-old woman with acute schizoaffective psychosis was treated with lithium carbonate (1,350 mg daily) and zuclopenthixol. On admission, clozapine was added (250 mg daily). Because extrapyramidal symptoms (rigor, akinesia) developed, she was additionally given biperiden retard (4 mg daily) from the fourth hospital day onwards. Eleven days after admission she began to complain of "unsteadiness" and "tremors" in her arms and she had asterixis (flapping tremor) on holding up her arms. The electromyogram showed electrical pauses of 60-120 ms, typical for asterixis. There were no significant metabolic or organic cerebral changes that could have accounted for the symptoms which presumably had been induced by the drugs even though their dosage was not unusual. The symptoms in fact regressed completely after the clozapine dose had been reduced, at first to 125 mg then to 50 mg. Previous experience has suggested that the risk of asterixis is particularly high when lithium and clozapine are taken together.

  3. Load Induced Blindness

    PubMed Central

    Macdonald, James S. P.; Lavie, Nilli

    2008-01-01

    Although the perceptual load theory of attention has stimulated a great deal of research, evidence for the role of perceptual load in determining perception has typically relied on indirect measures that infer perception from distractor effects on reaction times or neural activity (see N. Lavie, 2005d`) was consistently reduced with high, compared to low, perceptual load but was unaffected by the level of working memory load. Because alternative accounts in terms of expectation, memory, response bias, and goal-neglect due to the more strenuous high load task were ruled out, these experiments clearly demonstrate that high perceptual load determines conscious perception, impairing the ability to merely detect the presence of a stimulus—a phenomenon of load induced blindness. PMID:18823196

  4. DNA Damage Induced Neuronal Death

    DTIC Science & Technology

    1999-10-01

    Experiments are proposed to examine the molecular mechanism by which mustard chemical warfare agents induce neuronal cell death . DNA damage is the...proposed underlying mechanism of mustard-induced neuronal cell death . We propose a novel research strategy to test this hypothesis by using mice with...perturbed DNA repair to explore the relationship between mustard-induced DNA damage and neuronal cell death . Initial in vitro studies (Years 1, 2 & 3

  5. Pertussis-induced cough.

    PubMed

    Wang, Kay; Harnden, Anthony

    2011-06-01

    Pertussis (whooping cough) is one of the commonest vaccine preventable diseases in the UK, despite vaccination coverage being maintained for the last 15 years at over 90% among infants and the addition of a pre-school booster to the UK national immunisation programme in 2001. However, it is known that pertussis vaccine does not confer long-term immunity to clinical infection. Evidence of pertussis infection has been reported in 37% of children presenting in UK primary care and 20% of adolescents and adults presenting in Canadian health centres with persistent cough. In children and adults with persistent cough, paroxysmal coughing is the most sensitive indicator of pertussis, but has poor specificity and limited diagnostic value. Vomiting and whooping, particularly in combination, are stronger predictors of pertussis. Cough duration is longer in children than in adults with pertussis (median cough duration 112 days versus 42 days); individuals may take even longer to recover fully and regain previous levels of exercise tolerance. A diagnosis of pertussis may be confirmed by culture, Polymerase Chain Reaction (PCR) or serology. Single estimates of anti-pertussis toxin (PT) antibody titres in blood or oral fluid samples are highly specific. There are currently no proven efficacious treatments for pertussis-induced cough. Treatment with macrolide antibiotics reduces the duration of an individual's infectious period, but does not alter the duration of cough. Further research is needed to re-examine the epidemiology of pertussis in countries with different vaccination schedules, find efficacious treatments and develop methods of measuring cough frequency and severity in patients with pertussis-induced cough.

  6. Neuroanatomical distribution of the orphan GPR50 receptor in adult sheep and rodent brains.

    PubMed

    Batailler, M; Mullier, A; Sidibe, A; Delagrange, P; Prévot, V; Jockers, R; Migaud, M

    2012-05-01

    GPR50, formerly known as melatonin-related receptor, is one of three subtypes of the melatonin receptor subfamily, together with the MT(1) and MT(2) receptors. By contrast to these two high-affinity receptor subtypes and despite its high identity with the melatonin receptor family, GPR50 does not bind melatonin or any other known ligand. Specific and reliable immunological tools are therefore needed to be able to elucidate the physiological functions of this orphan receptor that are still largely unknown. We have generated and validated a new specific GPR50 antibody against the ovine GPR50 and used it to analyse the neuroanatomical distribution of the GPR50 in sheep, rat and mouse whole brain. We demonstrated that GPR50-positive cells are widely distributed in various regions, including the hypothalamus and the pars tuberalis of the pituitary, in all the three species studied. GPR50 expressing cells are abundant in the dorsomedial nucleus of the hypothalamus, the periventricular nucleus and the median eminence. In rodents, immunohistochemical studies revealed a broader distribution pattern for the GPR50 protein. GPR50 immunoreactivity is found in the medial preoptic area (MPA), the lateral septum, the lateral hypothalamic area, the bed nucleus of the stria terminalis, the vascular organ of the laminae terminalis and several regions of the amygdala, including the medial nuclei of amygdala. Additionally, in the rat brain, GPR50 protein was localised in the CA1 pyramidal cell layer of the dorsal hippocampus. In mice, moderate to high numbers of GPR50-positive cells were also found in the subfornical organ. Taken together, these results provide an enlarged distribution of GPR50 protein, give further insight into the organisation of the melatoninergic system, and may lay the framework for future studies on the role of the GPR50 in the brain.

  7. Bellows flow-induced vibrations

    NASA Technical Reports Server (NTRS)

    Tygielski, P. J.; Smyly, H. M.; Gerlach, C. R.

    1983-01-01

    The bellows flow excitation mechanism and results of comprehensive test program are summarized. The analytical model for predicting bellows flow induced stress is refined. The model includes the effects of an upstream elbow, arbitrary geometry, and multiple piles. A refined computer code for predicting flow induced stress is described which allows life prediction if a material S-N diagram is available.

  8. Fishbone-induced perforated appendicitis.

    PubMed

    Bababekov, Yanik J; Stanelle, Eric J; Abujudeh, Hani H; Kaafarani, Haytham M A

    2015-05-20

    We review the literature and describe a case of fishbone-induced appendicitis. A 63-year-old man presented with abdominal pain. Work up including a focused history and imaging revealed fishbone-induced perforated appendicitis. The patient was managed safely and successfully with laparoscopic removal of the foreign body and appendectomy.

  9. Clofibrate-Induced Antidiuresis

    PubMed Central

    Moses, Arnold M.; Howanitz, Joan; Gemert, Marcia Van; Miller, Myron

    1973-01-01

    Normal subjects and patients with antidiuretic hormone (ADH) deficiency were studied to determine the mechanism of the antidiuretic action of clofibrate. Before clofibrate treatment, the patients' ability to concentrate urine with a standardized dehydration procedure correlated with the amount of ADH which was excreted. During clofibrate administration all six patients with ADH deficiency developed an antidiuresis which was like that of ADH, since there was no change in sodium, potassium, total solute, or creatinine excretion. There was a correlation between the patients' ability to concentrate urine during dehydration and the subsequent response to clofibrate, and the excretion of ADH during dehydration correlated with the excretion of ADH on clofibrate therapy. Clofibrate-induced antidiuresis in these patients was partially overcome by ethanol and by water loading. Clofibrate interfered with the ability of patients and subjects to excrete a water load and prevented the water load from inhibiting ADH excretion in the normal subjects. These studies suggested that clofibrate was acting through endogenous ADH and this thesis was supported by the failure of clofibrate to produce an antidiuresis when injected into rats with total ADH deficiency (Brattleboro strain) although an antidiuresis was produced in water-loaded normal rats. When the drug was injected into Brattleboro rats with exogenous ADH, clofibrate either did not alter or it inhibited the action of the ADH. The data demonstrate that clofibrate has a significant ADH-like action. This action appears to be mediated through the release of endogenous ADH. Images PMID:4685079

  10. Chemotherapy-induced alopecia.

    PubMed

    Trüeb, Ralph M

    2009-03-01

    Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

  11. [Cold-induced urticaria].

    PubMed

    Delorme, N; Drouet, M; Thibaudeau, A; Verret, J L

    2002-09-01

    Cold urticaria is characterized by the development of urticaria, usually superficial and/or angioedematous reaction after cold contact. It was found predominantly in young women. The diagnosis is based on the history and ice cube test. Patients with a negative ice cube test may have represented systemic cold urticaria (atypical acquired cold urticaria) induced by general body cooling. The pathogenesis is poorly understood. Cold urticaria can be classified into acquired and familial disorders, with an autosomal dominant inheritance. Idiopathic cold urticaria is most common type but the research of a cryopathy is necessary. Therapy is often difficult. It is essential that the patient be warned of the dangers of swimming in cold water because systemic hypotension can occur. H1 antihistamines can be used for treatment of cold urticaria but the clinical responses are highly variable. The combination with an H2 antagonists is more effective. Doxepin may be useful in the treatment. Leukotriene receptor antagonists may be a novel, promising drug entity. In patients who do not respond to previous treatments, induction of cold tolerance may be tried.

  12. Discreteness inducing coexistence

    NASA Astrophysics Data System (ADS)

    dos Santos, Renato Vieira

    2013-12-01

    Consider two species that diffuse through space. Consider further that they differ only in initial densities and, possibly, in diffusion constants. Otherwise they are identical. What happens if they compete with each other in the same environment? What is the influence of the discrete nature of the interactions on the final destination? And what are the influence of diffusion and additive fluctuations corresponding to random migration and immigration of individuals? This paper aims to answer these questions for a particular competition model that incorporates intra and interspecific competition between the species. Based on mean field theory, the model has a stationary state dependent on the initial density conditions. We investigate how this initial density dependence is affected by the presence of demographic multiplicative noise and additive noise in space and time. There are three main conclusions: (1) Additive noise favors denser populations at the expense of the less dense, ratifying the competitive exclusion principle. (2) Demographic noise, on the other hand, favors less dense populations at the expense of the denser ones, inducing equal densities at the quasi-stationary state, violating the aforementioned principle. (3) The slower species always suffers the more deleterious effects of statistical fluctuations in a homogeneous medium.

  13. Laughter-induced syncope.

    PubMed

    Kim, Alexander J; Frishman, William H

    2012-01-01

    Reported cases of syncope caused directly by laughter are rare. The common scenario described in a few reports involved episodes of fortuitous laughter, sometimes followed by a short prodrome of lightheadedness, facial flushing, and dizziness, followed by an episode of definite syncope. There were no seizure-like movements, automatisms, or bladder or bowel incontinence. After the syncopal episodes that were seconds in length, the patients regained consciousness, and at that point were fully oriented. These episodes could recur in a similar situation with such laughter. Many of these patients subsequently underwent full syncope workups, without elucidating a primary cardiac or neurologic cause. In this review of laughter-induced syncope, we describe a patient of ours who fit these descriptions. This phenomenon is likely a subtype of benign Valsalva-related syncope, with autonomic reflex arcs coming into play that ultimately result in global cerebral hypoperfusion. Besides the Valsalva produced by a great fit of laughter, laughter itself has its own neuroendocrine and vasculature effects that may play a role.

  14. Inductive source induced polarization

    NASA Astrophysics Data System (ADS)

    Marchant, David; Haber, Eldad; Oldenburg, Douglas W.

    2013-02-01

    Induced polarization (IP) surveys are commonly performed to map the distribution of electrical chargeability that is a diagnostic physical property in mineral exploration and in many environmental problems. Although these surveys have been successful in the past, the galvanic sources required for traditional IP and magnetic IP (MIP) surveys prevent them from being applied in some geological settings. We develop a new methodology for processing frequency domain EM data to identify the presence of IP effects in observations of the magnetic fields arising from an inductive source. The method makes use of the asymptotic behaviour of the secondary magnetic fields at low frequency. A new quantity, referred to as the ISIP datum, is defined so that it equals zero at low frequencies for any frequency-independent (non-chargeable) conductivity distribution. Thus, any non-zero response in the ISIP data indicates the presence of chargeable material. Numerical simulations demonstrate that the method can be applied even in complicated geological situations. A 3-D inversion algorithm is developed to recover the chargeability from the ISIP data and the inversion is demonstrated on synthetic examples.

  15. Load induced blindness.

    PubMed

    Macdonald, James S P; Lavie, Nilli

    2008-10-01

    Although the perceptual load theory of attention has stimulated a great deal of research, evidence for the role of perceptual load in determining perception has typically relied on indirect measures that infer perception from distractor effects on reaction times or neural activity (see N. Lavie, 2005, for a review). Here we varied the level of perceptual load in a letter-search task and assessed its effect on the conscious perception of a search-irrelevant shape stimulus appearing in the periphery, using a direct measure of awareness (present/absent reports). Detection sensitivity (d') was consistently reduced with high, compared to low, perceptual load but was unaffected by the level of working memory load. Because alternative accounts in terms of expectation, memory, response bias, and goal-neglect due to the more strenuous high load task were ruled out, these experiments clearly demonstrate that high perceptual load determines conscious perception, impairing the ability to merely detect the presence of a stimulus--a phenomenon of load induced blindness.

  16. Loperamide-induced hypopituitarism

    PubMed Central

    Napier, Catherine; Gan, Earn H; Pearce, Simon H S

    2016-01-01

    Loperamide is the most commonly used antidiarrhoeal medication in the UK. We report a serious and hitherto undocumented adverse effect of chronic use in a 45-year-old man with inflammatory bowel disease. He presented to the endocrine clinic with fatigue and low libido; biochemical assessment revealed hypogonadism and adrenal insufficiency without any elevated adrenocorticotropic hormone. When symptoms allowed, loperamide was reduced and a short synacthen test (SST) showed a ‘clear pass’ with a normal peak cortisol of 833 nmol/L. Later, worsening diarrhoea necessitated an escalation in loperamide use again. While taking a daily dose of 15–20 mg (recommended daily maximum 16 mg) reassessment revealed a fall in peak cortisol on SST to 483 nmol/L, a subnormal response. Clinicians should exercise caution when relying on loperamide to manage their patients’ chronic diarrhoea and remain mindful of the possibility of drug-induced life-threatening adrenal insufficiency. PMID:27681351

  17. Extreme geomagnetically induced currents

    NASA Astrophysics Data System (ADS)

    Kataoka, Ryuho; Ngwira, Chigomezyo

    2016-12-01

    We propose an emergency alert framework for geomagnetically induced currents (GICs), based on the empirically extreme values and theoretical upper limits of the solar wind parameters and of d B/d t, the time derivative of magnetic field variations at ground. We expect this framework to be useful for preparing against extreme events. Our analysis is based on a review of various papers, including those presented during Extreme Space Weather Workshops held in Japan in 2011, 2012, 2013, and 2014. Large-amplitude d B/d t values are the major cause of hazards associated with three different types of GICs: (1) slow d B/d t with ring current evolution (RC-type), (2) fast d B/d t associated with auroral electrojet activity (AE-type), and (3) transient d B/d t of sudden commencements (SC-type). We set "caution," "warning," and "emergency" alert levels during the main phase of superstorms with the peak Dst index of less than -300 nT (once per 10 years), -600 nT (once per 60 years), or -900 nT (once per 100 years), respectively. The extreme d B/d t values of the AE-type GICs are 2000, 4000, and 6000 nT/min at caution, warning, and emergency levels, respectively. For the SC-type GICs, a "transient alert" is also proposed for d B/d t values of 40 nT/s at low latitudes and 110 nT/s at high latitudes, especially when the solar energetic particle flux is unusually high.

  18. Drug-Induced Metabolic Acidosis

    PubMed Central

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W.

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics. PMID:26918138

  19. Pregnancy-Induced hypertension.

    PubMed

    Kintiraki, Evangelia; Papakatsika, Sophia; Kotronis, George; Goulis, Dimitrios G; Kotsis, Vasilios

    2015-01-01

    Pregnancy-induced hypertension (PIH) complicates 6-10% of pregnancies. It is defined as systolic blood pressure (SBP) >140 mmHg and diastolic blood pressure (DBP) >90 mmHg. It is classified as mild (SBP 140-149 and DBP 90-99 mmHg), moderate (SBP 150-159 and DBP 100-109 mmHg) and severe (SBP ≥ 160 and DBP ≥ 110 mmHg). PIH refers to one of four conditions: a) pre-existing hypertension, b) gestational hypertension and preeclampsia (PE), c) pre-existing hypertension plus superimposed gestational hypertension with proteinuria and d) unclassifiable hypertension. PIH is a major cause of maternal, fetal and newborn morbidity and mortality. Women with PIH are at a greater risk of abruptio placentae, cerebrovascular events, organ failure and disseminated intravascular coagulation. Fetuses of these mothers are at greater risk of intrauterine growth retardation, prematurity and intrauterine death. Ambulatory blood pressure monitoring over a period of 24 h seems to have a role in predicting deterioration from gestational hypertension to PE. Antiplatelet drugs have moderate benefits when used for prevention of PE. Treatment of PIH depends on blood pressure levels, gestational age, presence of symptoms and associated risk factors. Non-drug management is recommended when SBP ranges between 140-149 mmHg or DBP between 90-99 mmHg. Blood pressure thresholds for drug management in pregnancy vary between different health organizations. According to 2013 ESH/ESC guidelines, antihypertensive treatment is recommended in pregnancy when blood pressure levels are ≥ 150/95 mmHg. Initiation of antihypertensive treatment at values ≥ 140/90 mmHg is recommended in women with a) gestational hypertension, with or without proteinuria, b) pre-existing hypertension with the superimposition of gestational hypertension or c) hypertension with asymptomatic organ damage or symptoms at any time during pregnancy. Methyldopa is the drug of choice in pregnancy. Atenolol and metoprolol appear to be

  20. Drug-induced urinary calculi.

    PubMed

    Matlaga, Brian R; Shah, Ojas D; Assimos, Dean G

    2003-01-01

    Urinary calculi may be induced by a number of medications used to treat a variety of conditions. These medications may lead to metabolic abnormalities that facilitate the formation of stones. Drugs that induce metabolic calculi include loop diuretics; carbonic anhydrase inhibitors; and laxatives, when abused. Correcting the metabolic abnormality may eliminate or dramatically attenuate stone activity. Urinary calculi can also be induced by medications when the drugs crystallize and become the primary component of the stones. In this case, urinary supersaturation of the agent may promote formation of the calculi. Drugs that induce calculi via this process include magnesium trisilicate; ciprofloxacin; sulfa medications; triamterene; indinavir; and ephedrine, alone or in combination with guaifenesin. When this situation occurs, discontinuation of the medication is usually necessary.

  1. Phentermine induced acute interstitial nephritis.

    PubMed

    Shao, Emily Ximin; Wilson, Gregory John; Ranganathan, Dwarakanathan

    2017-03-09

    Acute interstitial nephritis (AIN) has a number of medication-related aetiologies. Antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs are common causes; however, any medication has the potential to cause drug-induced AIN. We report the first case of phentermine-induced AIN. A Caucasian woman aged 43 years presented with a 5-week history of lethargy, left-sided lower abdominal pain, nausea and vomiting. She had been taking phentermine for weight loss for 9 months and had recently ceased the medication. The patient underwent a renal biopsy that showed a predominantly lymphohistiocytic interstitial infiltrate with a moderate number of eosinophils consistent with AIN. Phentermine is increasingly used for weight loss in obese patients. This is the first case implicating phentermine as the causative agent for drug-induced AIN. While rare, phentermine-induced AIN is a possible adverse reaction of phentermine. Physicians and patients need to be aware of this risk.

  2. Groundwater: Climate-induced pumping

    NASA Astrophysics Data System (ADS)

    Gurdak, Jason J.

    2017-01-01

    Groundwater resources are directly affected by climate variability via precipitation, evapotranspiration and recharge. Analyses of US and India trends reveal that climate-induced pumping indirectly influences groundwater depletion as well.

  3. Drug-induced lupus erythematosus

    MedlinePlus

    ... Causes Drug-induced lupus erythematosus is similar to systemic lupus erythematosus (SLE). It is an autoimmune disorder. This means ... 2015:chap 132. Wright B, Bharadwaj S, Abelson A. Systemic lupus erythematosus. In: Carey WD, ed. Cleveland Clinic: Current Clinical ...

  4. Victim-induced criminality.

    PubMed

    Fooner, M

    1966-09-02

    about the probable effects on the administration of criminal justice. These are pragmatic problems; there is a third problem which may at this time seem speculative, but is, nevertheless, quite important. 3) To what extent will a particular proposal for victim compensation contribute to a temptation-opportunity pattern in victim behavior? In previous studies it has been pointed out that large numbers of our fellow Americans have tended to acquire casual money-handling habits-generically designated "carelessness"-which contribute to the national growth of criminality. How the victim helps the criminal was sketched in reports of those studies (10). It was made abundantly clear that human beings in our affluent society cannot be assumed to be prudent or self-protective against the hazards of crime. Even when the "victim" is not overtly acting to commit a crime-as in the case of the property owner who hires an arsonist-he often tempts the offender. Among the victims of burglary-statistically the most prevalent crime in the United States-are a substantial number of Americans who keep cash, jewelry, and other valuables carelessly at home or in hotel rooms to which the burglar has easy access through door or window. Victims of automobile theft-one of the fastest growing classes of crime-include drivers who leave the vehicle or its contents invitingly accessible to thieves. And so on with other classes of crime. As pointed out in previous studies, when victim behavior follows a temptation-opportunity pattern, it (i) contributes to a "climate of criminal inducements," (ii) adds to the economic resources available to criminal societies, and (iii) detracts from the ability of lawenforcement agencies to suppress the growth of crime.

  5. Reprogramming with defined factors: from induced pluripotency to induced transdifferentiation.

    PubMed

    Masip, Manuel; Veiga, Anna; Izpisúa Belmonte, Juan Carlos; Simón, Carlos

    2010-11-01

    Ever since work on pluripotency induction was originally published, reporting the reprogramming of somatic cells to induced pluripotent stem cells (iPS cells) by the ectopic expression of the four transcription factors Oct4, Sox2, Klf4 and c-Myc, high expectations regarding their potential use for regenerative medicine have emerged. Very recently, the direct conversion of fibroblasts into functional neurons with no prior pluripotent stage has been described. Interconversion between adult cells from ontogenically different lineages by an induced transdifferentiation process based on the overexpression of a cocktail of transcription factors, while avoiding transition through an embryonic stem cell-like state, provides a new impetus in the field of regenerative medicine. Here, we review the induced reprogramming of somatic cells with defined factors and analyze their potential clinical use. Beginning with induced pluripotency, we summarize the initial objections including their extremely low efficiency and the risk of tumor generation. We also review recent reports describing iPS cells' capacity to generate viable offspring through tetraploid complementation, the most restrictive pluripotency criterion. Finally, we explore the available evidence for 'induced transdifferentiated cells' as a novel tool for adult cell fate modification.

  6. Induced airflow in flying insects II. Measurement of induced flow.

    PubMed

    Sane, Sanjay P; Jacobson, Nathaniel P

    2006-01-01

    The flapping wings of insects and birds induce a strong flow over their body during flight. Although this flow influences the sensory biology and physiology of a flying animal, there are very little data on the characteristics of this self-generated flow field or its biological consequences. A model proposed in the companion paper estimated the induced flow over flying insects. In this study, we used a pair of hot wire anemometers to measure this flow at two locations near the body of a tethered flapping hawk moth, Manduca sexta. The axial inflow anemometer measured the airflow prior to its entry into the stroke plane, whereas the radial outflow anemometer measured the airflow after it crossed the stroke plane. The high temporal resolution of the hot wire anemometers allowed us to measure not only the mean induced flow but also subtle higher frequency disturbances occurring at 1-4 times the wing beat frequency. These data provide evidence for the predictions of a mathematical model proposed in the companion paper. Specifically, the absolute value of the measured induced flow matches the estimate of the model. Also, as predicted by the model, the induced flow varies linearly with wing beat frequency. Our experiments also show that wing flexion contributes significantly to the observed higher frequency disturbances. Thus, the hot wire anemometry technique provides a useful means to quantify the aerodynamic signature of wing flexion. The phasic and tonic components of induced flow influence several physiological processes such as convective heat loss and gas exchange in endothermic insects, as well as alter the nature of mechanosensory and olfactory stimuli to the sensory organs of a flying insect.

  7. Neural correlates of expression-independent memories in the crab Neohelice.

    PubMed

    Maza, F J; Locatelli, F F; Delorenzi, A

    2016-05-01

    The neural correlates of memory have been usually examined considering that memory retrieval and memory expression are interchangeable concepts. However, our studies in the crab Neohelice (Chasmagnathus) granulata and in other memory models have shown that memory expression is not necessary for memory to be re-activated and become labile. In order to examine putative neural correlates of memory in the crab Neohelice, we contrast changes induced by training in both animal's behavior and neuronal responses in the medulla terminalis using in vivo Ca(2+) imaging. Disruption of long-term memory by the amnesic agents MK-801 or scopolamine (5μg/g) blocks the learning-induced changes in the Ca(2+) responses in the medulla terminalis. Conversely, treatments that lead to an unexpressed but persistent memory (weak training protocol or scopolamine 0.1μg/g) do not block these learning-induced neural changes. The present results reveal a set of changes in the neural activity induced by training that correlates with memory persistence but not with the probability of this memory to be expressed in the long-term. In addition, the study constitutes the first in vivo evidence in favor of a role of the medulla terminalis in learning and memory in crustaceans, and provides a physiological evidence indicating that memory persistence and the probability of memory to be expressed might involve separate components of memory traces.

  8. Elucidation of White Matter Tracts of the Human Amygdala by Detailed Comparison between High-Resolution Postmortem Magnetic Resonance Imaging and Histology

    PubMed Central

    Mori, Susumu; Kageyama, Yusuke; Hou, Zhipeng; Aggarwal, Manisha; Patel, Jaymin; Brown, Timothy; Miller, Michael I.; Wu, Dan; Troncoso, Juan C.

    2017-01-01

    The amygdala has attracted considerable research interest because of its potential involvement in various neuropsychiatric disorders. Recently, attempts have been made using magnetic resonance imaging (MRI) to evaluate the integrity of the axonal connections to and from the amygdala under pathological conditions. Although amygdalar pathways have been studied extensively in animal models, anatomical references for the human brain are limited to histology-based resources from a small number of slice locations, orientations and annotations. In the present study, we performed high-resolution (250 μm) MRI of postmortem human brains followed by serial histology sectioning. The histology data were used to identify amygdalar pathways, and the anatomical delineation of the assigned structures was extended into 3D using the MRI data. We were able to define the detailed anatomy of the stria terminalis and amygdalofugal pathway, as well as the anatomy of the nearby basal forebrain areas, including the substantia innominata. The present results will help us understand in detail the white matter structures associated with the amygdala, and will serve as an anatomical reference for the design of in vivo MRI studies and interpretation of their data. PMID:28352217

  9. Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice

    PubMed Central

    Sica, Monica; Martini, Mariangela; Viglietti-Panzica, Carla; Panzica, GianCarlo

    2009-01-01

    Background Nitric oxide plays an important role in the regulation of male and female sexual behavior in rodents, and the expression of the nitric oxide synthase (NOS) is influenced by testosterone in the male rat, and by estrogens in the female. We have here quantitatively investigated the distribution of nNOS immunoreactive (ir) neurons in the limbic hypothalamic region of intact female mice sacrificed during different phases of estrous cycle. Results Changes were observed in the medial preoptic area (MPA) (significantly higher number in estrus) and in the arcuate nucleus (Arc) (significantly higher number in proestrus). In the ventrolateral part of the ventromedial nucleus (VMHvl) and in the bed nucleus of the stria terminalis (BST) no significant changes have been observed. In addition, by comparing males and females, we observed a stable sex dimorphism (males have a higher number of nNOS-ir cells in comparison to almost all the different phases of the estrous cycle) in the VMHvl and in the BST (when considering only the less intensely stained elements). In the MPA and in the Arc sex differences were detected only comparing some phases of the cycle. Conclusion These data demonstrate that, in mice, the expression of nNOS in some hypothalamic regions involved in the control of reproduction and characterized by a large number of estrogen receptors is under the control of gonadal hormones and may vary according to the rapid variations of hormonal levels that take place during the estrous cycle. PMID:19604366

  10. Models and mechanisms of anxiety: evidence from startle studies

    PubMed Central

    Grillon, Christian

    2009-01-01

    Rationale Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety). Objective To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety. Results The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic anxiety disorders. Conclusions Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat. PMID:18058089

  11. Resting state connectivity of the human habenula at ultra-high field.

    PubMed

    Torrisi, Salvatore; Nord, Camilla L; Balderston, Nicholas L; Roiser, Jonathan P; Grillon, Christian; Ernst, Monique

    2017-02-15

    The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants. Results show novel functional connections in humans, including functional connectivity with the septum and bed nucleus of the stria terminalis (BNST). Results also show many habenula connections previously described only in animal research, such as with the nucleus basalis of Meynert, dorsal raphe, ventral tegmental area (VTA), and periaqueductal grey (PAG). Connectivity with caudate, thalamus and cortical regions such as the anterior cingulate, retrosplenial cortex and auditory cortex are also reported. This work, which demonstrates the power of ultra-high field for mapping human functional connections, is a valuable step toward elucidating subcortical and cortical regions of the habenula network.

  12. Autoradiographic distribution of /sup 125/I-galanin binding sites in the rat central nervous system

    SciTech Connect

    Skofitsch, G.; Sills, M.A.; Jacobowitz, D.M.

    1986-11-01

    Galanin (GAL) binding sites in coronal sections of the rat brain were demonstrated using autoradiographic methods. Scatchard analysis of /sup 125/I-GAL binding to slide-mounted tissue sections revealed saturable binding to a single class of receptors with a Kd of approximately 0.2 nM. /sup 125/I-GAL binding sites were demonstrated throughout the rat central nervous system. Dense binding was observed in the following areas: prefrontal cortex, the anterior nuclei of the olfactory bulb, several nuclei of the amygdaloid complex, the dorsal septal area, dorsal bed nucleus of the stria terminalis, the ventral pallidum, the internal medullary laminae of the thalamus, medial pretectal nucleus, nucleus of the medial optic tract, borderline area of the caudal spinal trigeminal nucleus adjacent to the spinal trigeminal tract, the substantia gelatinosa and the superficial layers of the dorsal spinal cord. Moderate binding was observed in the piriform, periamygdaloid, entorhinal, insular cortex and the subiculum, the nucleus accumbens, medial forebrain bundle, anterior hypothalamic, ventromedial, dorsal premamillary, lateral and periventricular thalamic nuclei, the subzona incerta, Forel's field H1 and H2, periventricular gray matter, medial and superficial gray strata of the superior colliculus, dorsal parts of the central gray, peripeduncular area, the interpeduncular nucleus, substantia nigra zona compacta, ventral tegmental area, the dorsal and ventral parabrachial and parvocellular reticular nuclei. The preponderance of GAL-binding in somatosensory as well as in limbic areas suggests a possible involvement of GAL in a variety of brain functions.

  13. The medial amygdaloid nucleus is involved in the cardiovascular pathway activated by noradrenaline into the lateral septal area of rats.

    PubMed

    Scopinho, América A; Fortaleza, Eduardo A T; Corrêa, Fernando M A

    2012-10-01

    We have previously reported that noradrenaline (NA) microinjected into the lateral septal area (LSA) caused pressor and bradicardic responses that were mediated by vasopressin release into the circulation through the paraventricular nucleus of hypothalamus (PVN). Although PVN is the final structure involved in the cardiovascular responses caused by NA in the LSA, there is no evidence of direct connections between these areas, suggesting that some structures could be links in this pathway. In the present study, we verified the effect of reversible synaptic inactivation of the medial amygdaloid nucleus (MeA), bed nucleus of stria terminalis (BNST) or diagonal band of Broca (DBB) with Cobalt Chloride (CoCl(2) ) on the cardiovascular response to NA microinjection into the LSA of unanesthetized rats. Male Wistar rats had guide cannulae implanted into the LSA and the MeA, BNST or DBB for drug administration, and a femoral catheter for blood pressure and heart rate recordings. Local microinjection of CoCl(2) (1 mm in 100 nL) into the MeA significantly reduced the pressor and bradycardic responses caused by NA microinjection (21 nmol in 200 nL) into the LSA. In contrast, microinjection of CoCl(2) into the BNST or DBB did not change the cardiovascular responses to NA into the LSA. The results indicate that synapses within the MeA, but not in BNST or DBB, are involved in the cardiovascular pathway activated by NA microinjection into the LSA.

  14. Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks

    PubMed Central

    González, J. Antonio; Iordanidou, Panagiota; Strom, Molly; Adamantidis, Antoine; Burdakov, Denis

    2016-01-01

    The lateral hypothalamus (LH) controls energy balance. LH melanin-concentrating-hormone (MCH) and orexin/hypocretin (OH) neurons mediate energy accumulation and expenditure, respectively. MCH cells promote memory and appropriate stimulus-reward associations; their inactivation disrupts energy-optimal behaviour and causes weight loss. However, MCH cell dynamics during wakefulness are unknown, leaving it unclear if they differentially participate in brain activity during sensory processing. By fiberoptic recordings from molecularly defined populations of LH neurons in awake freely moving mice, we show that MCH neurons generate conditional population bursts. This MCH cell activity correlates with novelty exploration, is inhibited by stress and is inversely predicted by OH cell activity. Furthermore, we obtain brain-wide maps of monosynaptic inputs to MCH and OH cells, and demonstrate optogenetically that VGAT neurons in the amygdala and bed nucleus of stria terminalis inhibit MCH cells. These data reveal cell-type-specific LH dynamics during sensory integration, and identify direct neural controllers of MCH neurons. PMID:27102565

  15. Two strains of roof rats as effective models for assessing new-object reaction.

    PubMed

    Kiyokawa, Yasushi; Tanaka, Kazuyuki D; Ishii, Akiko; Mikami, Kaori; Katayama, Masatoshi; Koizumi, Ryoko; Minami, Syota; Tanikawa, Tsutomu; Takeuchi, Yukari

    2017-04-05

    Wild animals generally avoid even small and harmless novel objects and/or familiar objects moved to a novel position, which is termed "new-object reaction". Although new-object reaction appears to be a biologically important characteristic for animals, little progress has been made in understanding the neural mechanisms underlying new-object reaction. One reason might be the lack of effective experimental animals. Two strains of roof rats (Sj and Og strains) were established from wild roof rats caught in Shinjuku, Tokyo and one of the Ogasawara Islands, respectively, by a Japanese pest control company. Based on the rat caregivers' informal observations, we conducted behavioral and anatomical tests to assess the validity of Sj and Og strains for the analyses of new-object reaction. In Experiment 1, the Sj strain showed reduced food consumption compared with the Og strain when food was provided in a novel way, suggesting that the Sj strain had a stronger avoidance of novel objects compared with the Og strain. Experiment 2 demonstrated that the basolateral complex of the amygdala and bed nucleus of the stria terminalis in experimental Sj rats had a larger percentage area compared with that of experimental Og rats, indicating these nuclei might be involved in the difference observed in avoidance of novel objects between the strains. Taken together, the present study suggests that Sj and Og strains are effective experimental animals for assessing new-object reaction.

  16. Contributions of the Central Extended Amygdala to Fear and Anxiety

    PubMed Central

    2016-01-01

    It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated and used to assemble states of fear and anxiety. Imaging studies in humans and monkeys show that the Ce and BST exhibit similar functional profiles. Both regions are sensitive to a range of aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs and symptoms of fear and anxiety; both show phasic responses to short-lived threat; and both show heightened activity during sustained exposure to diffusely threatening contexts. Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat. These observations compel a reconsideration of the central extended amygdala's contributions to fear and anxiety and its role in neuropsychiatric disease. PMID:27488625

  17. Winning territorial disputes selectively enhances androgen sensitivity in neural pathways related to motivation and social aggression.

    PubMed

    Fuxjager, Matthew J; Forbes-Lorman, Robin M; Coss, Dylan J; Auger, Catherine J; Auger, Anthony P; Marler, Catherine A

    2010-07-06

    Winning aggressive disputes can enhance future fighting ability and the desire to seek out additional contests. In some instances, these effects are long lasting and vary in response to the physical location of a fight. Thus, in principle, winning aggressive encounters may cause long-term and context-dependent changes to brain areas that control the output of antagonistic behavior or the motivation to fight (or both). We examined this issue in the territorial California mouse (Peromyscus californicus) because males of this species are more likely to win fights after accruing victories in their home territory but not after accruing victories in unfamiliar locations. Using immunocytochemistry and real-time quantitative PCR, we found that winning fights either at home or away increases the expression of androgen receptors (AR) in the medial anterior bed nucleus of the stria terminalis, a key brain area that controls social aggression. We also found that AR expression in brain regions that mediate motivation and reward, nucleus accumbens (NAcc) and ventral tegmental area (VTA), increases only in response to fights in the home territory. These effects of winning were likely exclusive to the neural androgenic system because they have no detectible impact on the expression of progestin receptors. Finally, we demonstrated that the observed changes in androgen sensitivity in the NAcc and VTA are positively associated with the ability to win aggressive contests. Thus, winning fights can change brain phenotype in a manner that likely promotes future victory and possibly primes neural circuits that motivate individuals to fight.

  18. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain.

    PubMed

    van der Doelen, Rick H A; Arnoldussen, Ilse A; Ghareh, Hussein; van Och, Liselot; Homberg, Judith R; Kozicz, Tamás

    2015-02-01

    The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene × Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid release upon exposure to stress. Both endophenotypes are regulated by the neuropeptide corticotropin-releasing factor (CRF) or hormone, which is expressed by the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, and the central amygdala (CeA). Therefore, we hypothesized that altered regulation of the expression of CRF in these areas represents a major neurobiological mechanism underlying the interaction of early life stress and 5-HTT gene variation. The programming of gene transcription by Gene × Environment interactions has been proposed to involve epigenetic mechanisms such as DNA methylation. In this study, we report that early life stress and 5-HTT genotype interact to affect DNA methylation of the Crf gene promoter in the CeA of adult male rats. Furthermore, we found that DNA methylation of a specific site in the Crf promoter significantly correlated with CRF mRNA levels in the CeA. Moreover, CeA CRF mRNA levels correlated with stress coping behavior in a learned helplessness paradigm. Together, our findings warrant further investigation of the link of Crf promoter methylation and CRF expression in the CeA with behavioral changes that are relevant for psychopathology.

  19. Effects of Postnatal Estrogen Manipulations on Juvenile Alloparental Behavior

    PubMed Central

    Perry, Adam N.; Carter, C. Sue; Cushing, Bruce S.

    2015-01-01

    Sex- and species-specific patterns of estrogen receptor (ER)-α expression are established early in development, which may contribute to sexual differentiation of behavior and determine male social organization. The current study investigated the effects of ERα and ERβ activation during the second postnatal week on subsequent alloparental behavior and ERα expression in juvenile prairie voles. Male and female pups were treated daily with 17β-estradiol (E2, ERα/ERβ agonist), PPT (selective ERα agonist), DPN (selective ERβ agonist), or the oil vehicle on postnatal days (PD) 8-14. Alloparental behavior and ERα expression were examined at PD21. PPT treatment inhibited prosocial motivation in males and increased pup-directed aggression in both sexes. E2 and DPN had no apparent effect on behavior in either sex. PPT-treated males had increased ERα expression in the medial preoptic area (MPN), medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpr). DPN treatment also increased ERα expression in males, but only in the BSTpr. Female ERα expression was unaffected by treatment. These results support the hypothesis that ERα activation in early life is associated with less prosocial patterns of central ERα expression and alloparental behavior in males. The lack of an effect of E2 on behavior suggests that ERβ may antagonize the effects of ERα on alloparental behavior. The results in DPN-treated males suggest that ERα in the MEApd, and not the BSTpr, may be a primary determinant of alloparental behavior in males. PMID:26222494

  20. An Investigation of the Effects of Maternal Separation and Novelty on Central Mechanisms Mediating Pituitary-Adrenal Activity in Infant Guinea Pigs (Cavia porcellus)

    PubMed Central

    Maken, Deborah S.; Weinberg, Joanne; Cool, David R.; Hennessy, Michael B.

    2016-01-01

    In mammalian species in which the young exhibit a strong filial attachment (e.g., monkeys, guinea pigs), numerous studies have shown that even brief separation from the attachment figure potently elevates circulating concentrations of glucocorticoids and adrenocorticotropic hormone (ACTH). However, effects of separation on central regulation of this stress response are not known. Therefore, we investigated central mechanisms mediating pituitary-adrenal activation during maternal separation and novelty exposure in guinea pig (Cavia porcellus) pups. Corticotropin-releasing factor (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN), and plasma cortisol and ACTH levels, were elevated only during separation in a novel environment. C-Fos activity was elevated in the medial amygdala (MeA) and reduced in the bed nucleus of the stria terminalis (BNST) during novelty exposure, regardless of separation. On the other hand, c-Fos activity was elevated in the PVN during separation, regardless of novelty exposure. These results demonstrate independent and combined effects of separation and novelty in regions of the guinea pig CNS that regulate pituitary-adrenal activity. Moreover, they suggest that a pathway from MeA to BNST to PVN mediates responses to novelty in the guinea pig pup, as in the adult rat, though inputs from other cell populations appear required to fully account for the HPA activity observed here. PMID:21038937

  1. Childhood physical abuse predicts stressor-evoked activity within central visceral control regions.

    PubMed

    Banihashemi, Layla; Sheu, Lei K; Midei, Aimee J; Gianaros, Peter J

    2015-04-01

    Early life experience differentially shapes later stress reactivity, as evidenced by both animal and human studies. However, early experience-related changes in the function of central visceral neural circuits that control stress responses have not been well characterized, particularly in humans. The paraventricular nucleus of the hypothalamus (PVN), bed nucleus of the stria terminalis (BNST), amygdala (Amyg) and subgenual anterior cingulate cortex (sgACC) form a core visceral stress-responsive circuit. The goal of this study is to examine how childhood emotional and physical abuse relates to adulthood stressor-evoked activity within these visceral brain regions. To evoke acute states of mental stress, participants (n = 155) performed functional magnetic resonance imaging (fMRI)-adapted versions of the multi-source interference task (MSIT) and the Stroop task with simultaneous monitoring of mean arterial pressure (MAP) and heart rate. Regression analyses revealed that childhood physical abuse correlated positively with stressor-evoked changes in MAP, and negatively with unbiased, a priori extractions of fMRI blood-oxygen level-dependent signal change values within the sgACC, BNST, PVN and Amyg (n = 138). Abuse-related changes in the function of visceral neural circuits may reflect neurobiological vulnerability to adverse health outcomes conferred by early adversity.

  2. Sex differences in the vomeronasal system.

    PubMed

    Guillamón, A; Segovia, S

    1997-01-01

    In the early eighties we found sex differences in the vomeronasal organ (VNO) and hypothesized that the vomeronasal system (VNS), a complex neural network involved in the control of reproductive behavior, might be sexually dimorphic. At that time sex differences had already been described for some structures that receive VNO input, such as the medial amygdala, the medial preoptic area, the ventromedial hypothalamic nucleus, and the ventral region of the premammillary nucleus. Since then, we have shown sex differences in the accessory olfactory bulb (AOB), the bed nucleus of the accessory olfactory tract (BAOT), and the bed nucleus of the stria terminalis (BST). When new VNS connections were found, all of them ended in nuclei that present sex differences. In general, sex differences in the olfactory system show two morphological patterns: one in which males present greater morphological measures than females, and just the opposite. To explain the morphometric measures of males in the latter, it has been hypothesized that androgens serve as inhibitors. Our work on the involvement of the GABA(A) receptor in the development of AOB and maternal behavior sex differences also suggests that neonatal changes in neuronal membrane permeability to the ion Cl- differences. This might be the first animal model to help us to understand the situation in which human genetic and gonadal sex do not agree with brain and behavioral sex. Finally, we stress that sex differences in the VNS constitute a neurofunctional model for understanding sex differences in reproductive behaviors.

  3. Statistical modeling implicates neuroanatomical circuit mediating stress relief by 'comfort' food.

    PubMed

    Ulrich-Lai, Yvonne M; Christiansen, Anne M; Wang, Xia; Song, Seongho; Herman, James P

    2016-07-01

    A history of eating highly palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30 % sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such 'comfort' foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala-medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological datasets.

  4. Oxytocin receptor binding in the hypothalamus during gestation in rats.

    PubMed

    Bealer, Steven L; Lipschitz, David L; Ramoz, Gina; Crowley, William R

    2006-07-01

    Central oxytocin receptors (OTR) may be involved in adaptations of the brain oxytocin (OT) system during gestation, which are critical for systemic release of OT during parturition and lactation. We used quantitative autoradiography to determine changes in OTR binding in numerous brain sites during the course of gestation in the rat. Furthermore, to evaluate the importance of ovarian steroids in mediating pregnancy-related changes in OTR binding, we measured binding in ovariectomized animals treated with progesterone and/or estrogen, and in pregnant animals treated with exogenous progesterone during late gestation. We found that OTR binding was significantly increased in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by midgestation (day 15) compared with control. In addition, there was a further significant increase in OTR binding in these nuclei by late gestation (day 20). The bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA) also showed significant gestation-associated increases in OTR binding, which were similar during mid- and late pregnancy. Treatment with exogenous progesterone throughout pregnancy did not alter the increase in OTR binding characteristic of late gestation in any of these brain sites. Finally, estrogen treatment in ovariectomized animals resulted in increased OTR binding in the SON, BNST, and MPOA, but not the PVN. These data demonstrate that OTR binding in the hypothalamus is increased during mid- and late-gestation, compared with ovariectomized control animals, which may be mediated by increased estradiol.

  5. Repeated anabolic-androgenic steroid treatment during adolescence increases vasopressin V(1A) receptor binding in Syrian hamsters: correlation with offensive aggression.

    PubMed

    DeLeon, Katrina R; Grimes, Jill M; Melloni, Richard H

    2002-09-01

    Repeated anabolic-androgenic steroid treatment during adolescence increases hypothalamic vasopressin and facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study investigated whether anabolic-androgenic steroid exposure during this developmental period influenced vasopressin V(1A) receptor binding activity in the hypothalamus and several other brain areas implicated in aggressive behavior in hamsters. To test this, adolescent male hamsters were administered anabolic steroids or sesame oil throughout adolescence, tested for offensive aggression, and examined for differences in vasopressin V(1A) receptor binding using in situ autoradiography. When compared with control animals, aggressive, adolescent anabolic steroid-treated hamsters showed significant increases (20-200%) in the intensity of vasopressin V(1A) receptor labeling in several aggression areas, including the ventrolateral hypothalamus, bed nucleus of the stria terminalis, and lateral septum. However, no significant differences in vasopressin V(1A) receptor labeling were found in other brain regions implicated in aggressive responding, most notably the lateral zone from the medial preoptic area to anterior hypothalamus and the corticomedial amygdala. These data suggest that adolescent anabolic steroid exposure may facilitate offensive aggression by increasing vasopressin V(1A) receptor binding in several key areas of the hamster brain.

  6. Suprachiasmatic Nucleus as the Site of Androgen Action on Circadian Rhythms

    PubMed Central

    Model, Zina; Butler, Matthew P.; LeSauter, Joseph; Silver, Rae

    2015-01-01

    Androgens act widely in the body in both central and peripheral sites. Prior studies indicate that in the mouse, suprachiasmatic nucleus (SCN) cells bear androgen receptors (ARs). The SCN of the hypothalamus in mammals is the locus of a brain clock that regulates circadian rhythms in physiology and behavior. Gonadectomy results in reduced AR expression in the SCN and in marked lengthening of the period of free-running activity rhythms. Both responses are restored by systemic administration of androgens, but the site of action remains unknown. Our goal was to determine whether intracranial androgen implants targeted to the SCN are sufficient to restore the characteristic free-running period in gonadectomized male mice. The results indicate that hypothalamic implants of testosterone propionate in or very near the SCN produce both anatomical and behavioral effects, namely increased AR expression in the SCN and restored period of free-running locomotor activity. The effect of the implant on the period of the free-running locomotor rhythm is positively correlated with the amount of AR expression in the SCN. There is no such correlation of period change with amount of AR expression in other brain regions examined, namely the preoptic area, bed nucleus of the stria terminalis and premammillary nucleus. We conclude that the SCN is the site of action of androgen effects on the period of circadian activity rhythmicity. PMID:26012711

  7. Chronic social stress in puberty alters appetitive male sexual behavior and neural metabolic activity.

    PubMed

    Bastida, Christel C; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J; Wommack, Joel C; Delville, Yvon

    2014-07-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation were altered by social subjugation.

  8. Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus.

    PubMed

    Shughrue, P J; Lane, M V; Merchenthaler, I

    1996-11-01

    GLP-1 has been shown to dramatically reduce food intake in fasted rats and is thought to exert its effects by modulating neuronal function in the hypothalamus. To date, little is known about the distribution of GLP1-R and its mRNA in the rodent hypothalamus. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of GLP1-R mRNA in the rat hypothalamus. The results of these studies revealed an extensive distribution of GLP1-R mRNA throughout the rostral-caudal extent of the hypothalamus; with a dense accumulation of labeled cells in the supraoptic, paraventricular, and arcuate nuclei. Additional labeled cells were also detected in medial and lateral preoptic areas, periventricular nucleus, ventral division of the bed nucleus of the stria terminalis, lateral hypothalamus, and dorsomedial nucleus. The results of these in situ hybridization histochemical studies have provided detailed and novel information about the distribution of GLP1-R mRNA in the rat hypothalamus. In addition, this morphological data provides important information about the neuronal systems modulated by GLP-1 and their potential role in feeding behavior.

  9. Voluntary exercise facilitates pair-bonding in male prairie voles.

    PubMed

    Kenkel, William M; Carter, C Sue

    2016-01-01

    The neuropeptides oxytocin and vasopressin have been implicated in exercise, as well as monogamy and parental behavior. In this study, we compared behavioral and neuroendocrine effects of access to an exercise wheel vs. the sedentary state typical in lab animal housing. Male prairie voles (Microtus ochrogaster) were studied because of their extensive repertoire of social behaviors including pair bond formation and biparental care, which are influenced by oxytocin and vasopressin. Subjects in one group had access to a running wheel in their cage (wheel), and voluntarily ran approximately 1.5 km/day for six weeks; these animals were compared to males in standard housing conditions (n=10/group). Males allowed to exercise formed partner preferences significantly faster than controls and exhibited fewer oxytocin neurons, as measured by immunohistochemistry in the bed nucleus of the stria terminalis. We observed no differences in terms of anxiety-related behavior, or alloparental responsiveness. Males with a running wheel equipped cage gained more total body weight, and by the end of the six weeks were found to have less subcutaneous fat and larger testes as a percentage of bodyweight. The changes to gonadal regulation and pair-bonding behavior associated with voluntary exercise are discussed in terms of their possible relevance to the natural history of this species.

  10. Cyto- and chemoarchitecture of the amygdala of a monotreme, Tachyglossus aculeatus (the short-beaked echidna).

    PubMed

    Ashwell, Ken W S; Hardman, Craig D; Paxinos, George

    2005-10-01

    We have examined the cyto- and chemoarchitecture of the temporal and extended amygdala in the brain of a monotreme (the short-beaked echidna Tachyglossus aculeatus) using Nissl and myelin staining, enzyme histochemistry for acetylcholine esterase and NADPH diaphorase, immunohistochemistry for calcium binding proteins (parvalbumin, calbindin and calretinin) and tyrosine hydroxylase. While the broad subdivisions of the eutherian temporal amygdala were present in the echidna brain, there were some noticeable differences. No immunoreactivity for parvalbumin or calretinin for somata was found in the temporal amygdala of the echidna. The nucleus of the lateral olfactory tract could not be definitively identified and the medial nucleus of amygdala appeared to be very small in the echidna. Calbindin immunoreactive neurons were most frequently found in the ventrolateral part of the lateral nucleus, intraamygdaloid parts of the bed nucleus of the stria terminalis and the lateral part of the central nucleus. Neurons strongly reactive for NADPH diaphorase with filling of the dendritic tree were found mainly scattered through the cortical, central and lateral subnuclei, while neurons showing only somata reactivity for NADPH diaphorase were concentrated in the basomedial and basolateral subnuclei. Most of the components of the extended amygdala of eutherians could also be identified in the echidna. Volumetric analysis indicated that the temporal amygdala in both the platypus and echidna is small compared to the same structure in both insectivores and primates, with the central and medial components of the temporal amygdala being particularly small.

  11. Elucidation of White Matter Tracts of the Human Amygdala by Detailed Comparison between High-Resolution Postmortem Magnetic Resonance Imaging and Histology.

    PubMed

    Mori, Susumu; Kageyama, Yusuke; Hou, Zhipeng; Aggarwal, Manisha; Patel, Jaymin; Brown, Timothy; Miller, Michael I; Wu, Dan; Troncoso, Juan C

    2017-01-01

    The amygdala has attracted considerable research interest because of its potential involvement in various neuropsychiatric disorders. Recently, attempts have been made using magnetic resonance imaging (MRI) to evaluate the integrity of the axonal connections to and from the amygdala under pathological conditions. Although amygdalar pathways have been studied extensively in animal models, anatomical references for the human brain are limited to histology-based resources from a small number of slice locations, orientations and annotations. In the present study, we performed high-resolution (250 μm) MRI of postmortem human brains followed by serial histology sectioning. The histology data were used to identify amygdalar pathways, and the anatomical delineation of the assigned structures was extended into 3D using the MRI data. We were able to define the detailed anatomy of the stria terminalis and amygdalofugal pathway, as well as the anatomy of the nearby basal forebrain areas, including the substantia innominata. The present results will help us understand in detail the white matter structures associated with the amygdala, and will serve as an anatomical reference for the design of in vivo MRI studies and interpretation of their data.

  12. Cocaine- and amphetamine-related transcript is involved in the orexigenic effect of endogenous anandamide.

    PubMed

    Osei-Hyiaman, Douglas; Depetrillo, Michael; Harvey-White, Judith; Bannon, Anthony W; Cravatt, Benjamin F; Kuhar, Michael J; Mackie, Ken; Palkovits, Miklós; Kunos, George

    2005-01-01

    Endocannabinoids acting at CB1 cannabinoid receptors (CB1) increase appetite. In view of the predominant presynaptic localization of CB1 in the brain, we tested the hypothesis that the orexigenic effect of endocannabinoids involves inhibition of the release of a tonically active anorexigenic mediator, such as the peptide product of the cocaine- and amphetamine-related transcript (CART). The CB1 antagonist rimonabant inhibited food intake in food-restricted wild-type mice, but not in their CART-deficient littermates. Mice deficient in fatty acid amide hydrolase (FAAH), the enzyme responsible for the in vivo metabolism of the endocannabinoid anandamide, have reduced levels of CART-immunoreactive nerve fibers and terminals in several brain regions implicated in appetite control, including the arcuate, dorsomedial and periventricular nuclei of the hypothalamus, the amygdala, the bed nucleus of the stria terminalis and the nucleus accumbens, and treatment of FAAH(-/-) mice with rimonabant, 3 mg/kg/day for 7 days, increased CART levels toward those seen in FAAH(+/+) wild-type controls. In contrast, no difference in the density of CART-immunoreactive fibers was observed in the median eminence and the paraventricular nucleus of FAAH(+/+) and FAAH(-/-) mice. Acute treatment of wild-type mice with the cannabinoid agonist HU-210 resulted in elevated CART levels in the dorsomedial nucleus and the shell portion of the nucleus accumbens. These observations are compatible with CART being a downstream mediator of the CB1-mediated orexigenic effect of endogenous anandamide.

  13. Neurons in the brain of the male cynomolgus monkey accumulate /sup 3/H-medroxyprogesterone acetate (MPA)

    SciTech Connect

    Michael, R.P.; Bonsall, R.W.; Rees, H.D.

    1986-03-01

    MPA is a synthetic progestin with androgen-depleting activity. It is used clinically to reduce sexual motivation and aggression in male sex offenders. The mechanisms for its behavioral effects are not known. The authors used steroid autoradiography to help identify sites where MPA may act in the brain of male primates. Twenty-four hours after castration, two adult male cynomolgus macaques, weighing 4.9 and 6.6 kg, were administered 5 mCi /sup 3/H-MPA (NEN, 47.7 Ci/mmol) i.v., and were killed 1 h later. Left sides of the brains and samples of pituitary glands were frozen and 4-micron sections were cut and processed for thaw-mount autoradiography. Radioactivity was concentrated in the nuclei of many neutrons in the ventromedial hypothalamic nucleus (n.), arcuate n., medial preoptic n., and anterior hypothalamic area. Virtually no labeled cells were seen in the bed n. of stria terminalis, lateral septal n., amygdala, or pituitary gland. Right sides of the brains were analyzed by HPLC which demonstrated that 98% of the radioactivity in cell nuclei from the hypothalamus was in the form of unmetabolized /sup 3/H-MPA. The distribution of labelling in the brain following /sup 3/H-MPA administration resembled that previously seen following /sup 3/H-ORG 2058 in female cynomolgus monkeys. These data indicate that MPA has a circumscribed localization in the brain.

  14. Relationship between sexual satiety and motivation, brain androgen receptors and testosterone in male mandarin voles.

    PubMed

    He, Fengqin; Yu, Peng; Wu, Ruiyong

    2013-08-01

    Androgen receptors participate in the neuroendocrine regulation of male sexual behavior, primarily in brain areas located in the limbic system. Males of many species present a long-term inhibition of sexual behavior after several ejaculations, known as sexual satiety. It has been shown in rats that androgen receptor expression is reduced 24h after a single ejaculation, or mating to satiety, in the medial preoptic area, nucleus accumbens and ventromedial hypothalamus. The aim of this study was to analyze these processes in another animal, the mandarin vole (Microtus mandarinus). We compared differences in androgen receptor (AR) and testosterone (T) expression in various brain areas between male mandarin voles sexually satiated and those exposed to receptive females but not allowed to mate. Sexual satiety was associated with decreased AR and T expression in the lateral septal nucleus (LS), medial amygdala (MeA), medial preoptic area (mPOA) and ventromedial hypothalamic nucleus (VMH). Males exposed to receptive females showed an increase in AR and T expression in the bed nucleus of the stria terminalis (BNST), LS, MeA and VMH. Serum testosterone levels remained unchanged after 24h in males exposed to receptive females or males mated to satiety. These data suggest a relationship between sexual activity and a decrease in AR and T expression in specific brain areas, and a relationship between sexual motivation and increased AR and T expression in other brain areas, independently of testosterone levels.

  15. Targeting neurogenesis ameliorates danger assessment in a mouse model of Alzheimer's disease.

    PubMed

    Shruster, Adi; Offen, Daniel

    2014-03-15

    Alzheimer's disease (AD) affects 13% of the population over the age of 65. Behavioral and neuropsychiatric symptoms are frequent and affect 80% of patients. Adult hippocampal neurogenesis, which is impaired in AD, is involved in learning and memory. It remains unclear, however, whether increasing adult neurogenesis improves behavioral symptoms in AD. We report that in the 3xTgAD mouse model of AD, chronic Wnt3a overexpression in the ventral hippocampus dentate gyrus (DG) restored adult neurogenesis to physiological levels. The restoration of adult neurogenesis led to full recovery of danger assessment impairment and the effect was blocked by ablation of neurogenesis with X-irradiation. Finally, using a bed nucleus of stria terminalis (BNST) mRNA expression array, we found that the expression of the 5-HT1A receptor in 3xTgAD mice is selectively decreased and normalized by Wnt3a overexpression in the ventral hippocampus DG, and this normalization is neurogenesis dependent. These findings indicate that reestablishing a functional population of hippocampal newborn neurons in adult AD mice rescues behavioral symptoms, suggesting that adult neurogenesis may be a promising therapeutic target for alleviating behavioral deficits in AD patients.

  16. Distribution of the neuronal inputs to the ventral premammillary nucleus of male and female rats☆

    PubMed Central

    Cavalcante, Judney Cley; Bittencourt, Jackson Cioni; Elias, Carol Fuzeti

    2014-01-01

    The ventral premammillary nucleus (PMV) expresses dense collections of sex steroid receptors and receptors for metabolic cues, including leptin, insulin and ghrelin. The PMV responds to opposite sex odor stimulation and projects to areas involved in reproductive control, including direct innervation of gonadotropin releasing hormone neurons. Thus, the PMV is well positioned to integrate metabolic and reproductive cues, and control downstream targets that mediate reproductive function. In fact, lesions of PMV neurons blunt female reproductive function and maternal aggression. However, although the projections of PMV neurons have been well documented, little is known about the neuronal inputs received by PMV neurons. To fill this gap, we performed a systematic evaluation of the brain sites innervating the PMV neurons of male and female rats using the retrograde tracer subunit B of the cholera toxin (CTb). In general, we observed that males and females show a similar pattern of afferents. We also noticed that the PMV is preferentially innervated by neurons located in the forebrain, with very few projections coming from brainstem nuclei. The majority of inputs originated from the medial nucleus of the amygdala, the bed nucleus of the stria terminalis and the medial preoptic nucleus. A moderate to high density of afferents was also observed in the ventral subiculum, the arcuate nucleus and the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus. Our findings strengthen the concept that the PMV is part of the vomeronasal system and integrates the brain circuitry controlling reproductive functions. PMID:25084037

  17. NPY Signaling Inhibits Extended Amygdala CRF Neurons to Suppress Binge Alcohol Drinking

    PubMed Central

    Pleil, Kristen E.; Rinker, Jennifer A.; Lowery-Gionta, Emily G.; Mazzone, Christopher M.; McCall, Nora M.; Kendra, Alexis M.; Olson, David P.; Lowell, Bradford B.; Grant, Kathleen A.; Thiele, Todd E.; Kash, Thomas L.

    2015-01-01

    Summary paragraph Binge alcohol drinking is a tremendous public health problem because it leads to the development of numerous pathologies including alcohol abuse, and anxiety1–4. It is thought to do so by hijacking brain systems that regulate stress and reward, including neuropeptide Y (NPY) and corticotropin–releasing factor (CRF). The central actions of NPY and CRF play opposing functional roles in the regulation of emotional and reward–seeking behaviors; therefore, dysfunctional interactions between these peptidergic systems could play a role in the development of these pathologies. Here, we used converging physiological, pharmacological, and chemogenetic approaches to identify a precise neural mechanism in the bed nucleus of the stria terminalis (BNST), a limbic brain region involved in pathological reward and anxiety behaviors, underlying the interactions between NPY and CRF in the regulation of binge alcohol drinking in both mice and monkeys. We found that NPY Y1 receptor (Y1R) activation in the BNST suppressed binge alcohol drinking by enhancing inhibitory synaptic transmission specifically in CRF neurons via a novel, Gi-mediated, PKA-dependent postsynaptic mechanism. Further, chronic alcohol drinking led to persistent alterations in Y1R function in the BNST of both mice and monkeys, highlighting the enduring, conserved nature of this effect across mammalian species. Together, these data provide both a cellular locus and signaling framework for the development of novel therapeutics for treatment of neuropsychiatric diseases, including alcohol use disorders. PMID:25751534

  18. The controversial existence of the human superior fronto-occipital fasciculus: Connectome-based tractographic study with microdissection validation.

    PubMed

    Meola, Antonio; Comert, Ayhan; Yeh, Fang-Cheng; Stefaneanu, Lucia; Fernandez-Miranda, Juan C

    2015-12-01

    The superior fronto-occipital fasciculus (SFOF), a long association bundle that connects frontal and occipital lobes, is well-documented in monkeys but is controversial in human brain. Its assumed role is in visual processing and spatial awareness. To date, anatomical and neuroimaging studies on human and animal brains are not in agreement about the existence, course, and terminations of SFOF. To clarify the existence of the SFOF in human brains, we applied deterministic fiber tractography to a template of 488 healthy subjects and to 80 individual subjects from the Human Connectome Project (HCP) and validated the results with white matter microdissection of post-mortem human brains. The imaging results showed that previous reconstructions of the SFOF were generated by two false continuations, namely between superior thalamic peduncle (STP) and stria terminalis (ST), and ST and posterior thalamic peduncle. The anatomical microdissection confirmed this finding. No other fiber tracts in the previously described location of the SFOF were identified. Hence, our data suggest that the SFOF does not exist in the human brain.

  19. PACAP in the BNST Produces Anorexia and Weight Loss in Male and Female Rats

    PubMed Central

    Kocho-Schellenberg, Margaret; Lezak, Kimberly R; Harris, Olivia M; Roelke, Erin; Gick, Niklas; Choi, Inyop; Edwards, Shaquille; Wasserman, Emily; Toufexis, Donna J; Braas, Karen M; May, Victor; Hammack, Sayamwong E

    2014-01-01

    Recent gene association studies have implicated pituitary adenylate cyclase-activating peptide (PACAP) systems in several psychiatric disorders associated with stressor exposure, and we have argued that many of the behavioral consequences of repeated stressor exposure may depend on the expression of PACAP in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of the activation of stress systems can be anorexia and subsequent weight loss, and both the activation of central PACAP systems as well as neuronal activity in the BNST have also been associated with anorexic states in rodents. Hence, we investigated the regulation of food and water intake and weight loss following BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake in the first 24 h following infusion. Because different BNST subregions differentially regulate stress responding, we further examined the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion resulted in weight loss. PACAP38 infused into the lateral ventricles did not alter weight, suggesting that the effects of BNST-infused PACAP were not mediated by leakage into the ventricular system. These data suggest that PACAP receptor activation in posterior BNST subregions can produce anorexia and weight loss, and corroborate growing data implicating central PACAP activation in mediating the consequences of stressor exposure. PMID:24434744

  20. Photoperiod affects estrogen receptor α, estrogen receptor β and aggressive behavior

    PubMed Central

    Trainor, Brian C.; Rowland, Michael R.; Nelson, Randy J.

    2007-01-01

    Estrogens have important effects on male and female social behavior. Despite growing knowledge of the anatomy and behavioral effects of the two predominant estrogen receptor subtypes in mammals (ERα and ERβ), relatively little is known about how these receptors respond to salient environmental stimuli. Many seasonally breeding species respond to changing photoperiods that predict seasonal changes in resource availability. We characterized the effects of photoperiod on aggressive behavior in two species of Peromyscus that exhibit gonadal regression in short days. P. polionotus (old field mice) were more aggressive than P. maniculatus (deer mice) and both species were more aggressive in short days. We used immunocytochemistry and real-time polymerase chain reaction to characterize the effects of photoperiod on ERα and ERβ expression. In both species ERα-immunoreactive staining in the posterior bed nucleus of the stria terminalis (BNST) was increased in short vs. long days. Both species had reduced ERβ-immunoreactive expression in the posterior BNST in short days. In the medial amygdala ERβ immunoreactivity was increased in long days for both species. Using real-time polymerase chain reaction on punch samples that included the BNST, we observed that ERα mRNA was increased and ERβ mRNA was decreased in short days. These data suggest that the effects of photoperiod on ERα and ERβ expression may thus have important behavioral consequences. PMID:17614949

  1. Striatum on the anxiety map: Small detours into adolescence

    PubMed Central

    Lago, Tiffany; Davis, Andrew; Grillon, Christian; Ernst, Monique

    2016-01-01

    Adolescence is the most sensitive period for the development of pathological anxiety. Moreover, specific neural changes associated with the striatum might be related to adolescent vulnerability to anxiety. Up to now, the study of anxiety has primarily focused on the amygdala, bed nucleus of the stria terminalis (BNST), hippocampus and ventromedial prefrontal cortex (vmPFC), while the striatum has typically not been considered as part of the anxiety system. This review proposes the addition of the striatum, a complex, multi-component structure, to the anxiety network by underscoring two lines of research. First, the co-occurrence of the adolescent striatal development with the peak vulnerability of adolescents to anxiety disorders might potentially reflect a causal relationship. Second, the recognition of the role of the striatum in fundamental behavioral processes that do affect anxiety supports the putative importance of the striatum in anxiety. These behavioral processes include (1) attention, (2) conditioning/prediction error, and (3) motivation. This review proposes a simplistic schematic representation of the anxiety circuitry that includes the striatum, and aims to promote further work in this direction, as the role of the striatum in shaping an anxiety phenotype during adolescence could have critical implications for understanding and preventing the peak onset of anxiety disorders during this period. PMID:27276526

  2. Neural correlates of the mother-to-infant social transmission of fear.

    PubMed

    Chang, Da-Jeong; Debiec, Jacek

    2016-06-01

    Although clinical and basic studies show that parental trauma, fear, and anxiety may be transmitted to offspring, the neurobiology of this transmission is still not well understood. We recently demonstrated in an animal model that infant rats acquire threat responses to a distinct cue when a mother expresses fear to this cue in their presence. This ability to acquire maternal fear through social learning is present at birth and, as we previously reported, depends on the pup's amygdala. However, the remaining neural mechanisms underlying social fear learning (SFL) in infancy remain elusive. Here, by using [(14) C]2-deoxyglucose autoradiography, we show that the mother-to-infant transmission of fear in preweaning rats is associated with a significant increase of activity in the subregions of the lateral septum, nucleus accumbens, bed nucleus of stria terminalis, retrosplenial cortex, paraventricular nucleus of the thalamus, mediodorsal and intralaminar thalamic nuclei, medial and the lateral preoptic nuclei of the hypothalamus, and the lateral periaqueductal gray. In contrast to studies of adult SFL demonstrating the role of the anterior cingulate cortex and possibly the insular cortex or research of infant classical fear conditioning showing the role of the posterior piriform cortex, no changes of activation in these areas were observed. Our results indicate that the pup's exposure to maternal fear activates a number of areas involved in processing threat, stress, or pain. This pattern of activation suggests a unique set of neural mechanisms underlying SFL in the developing brain.

  3. Autoradiographic localization of /sup 3/H-dihydrotestosterone in the preoptic area, hypothalamus, and amygdala of a male rhesus monkey

    SciTech Connect

    Michael, R.P.; Rees, H.D.

    1982-06-14

    In a preliminary study, autoradiography was used to localize target cells for /sup 3/H-dihydrotestosterone (DHT), a non-aromatizable androgen, in the brain of the rhesus monkey. One castrated male was injected intravenously with 2 mCi of /sup 3/H-DHT (0.42 ..mu..g/kg), and was killed one hour later. Neurons that concentrated radioactivity in their nuclei were located in widespread areas of the brain, which included the medial and suprachiasmatic preoptic nuclei, bed nucleus of the stria terminalis, lateral septal nucleus, anterior hypothalamic area, ventromedial, arcuate, dorsomedial, and paraventricular hypothalamic nuclei, ventral premammillary nucleus, and medial, cortical, basal accessory, and lateral amygdaloid nuclei. These results indicate that the topographic distribution of androgen target neurons is considerably wider than that observed in a study using /sup 3/H-testosterone (T) in the male rhesus monkey. However, further work is needed to elucidate these differences before attempting correlations between behavioral activity and androgen receptors in the brain.

  4. Ontogeny of cells containing estrogen receptor-like immunoreactivity in the Brazilian opossum brain.

    PubMed

    Fox, C A; Ross, L R; Jacobson, C D

    1991-11-19

    In this study, we have used the Brazilian short-tailed opossum (Monodelphis domestica) as a model to study the ontogeny of estrogen receptors in the mammalian brain. Monodelphis is a small, pouchless marsupial which breeds well under laboratory conditions and whose young are born in an immature sexually undifferentiated state. The Abbott H222 monoclonal rat estrogen receptor antibody (gift of Abbott Laboratories) was utilized in an indirect immunohistochemical procedure to detect estrogen receptors in developing opossum brains. Estrogen receptors were first expressed in the dorsomedial and ventromedial hypothalamus of the opossum 10 days after birth (10PN). Most regions that contained estrogen receptor-like immunoreactivity (ER LI) in the adult opossum contained ER LI at 15 PN. These areas include the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, periventricular preoptic area and hypothalamus, amygdala, dorsomedial and ventromedial hypothalamic nuclei, arcuate nucleus, ventral premammillary nucleus, and the midbrain central grey. The number of cells that contain ER LI increased through 60PN in all regions that will contain ER LI in the adult opossum. These results indicate that estrogen receptors are present in early development of the Monodelphis brain and may mark the beginning of a critical period for sexual differentiation of the opossum brain.

  5. Waiting for spiders: brain activation during anticipatory anxiety in spider phobics.

    PubMed

    Straube, Thomas; Mentzel, Hans-Joachim; Miltner, Wolfgang H R

    2007-10-01

    Anticipatory anxiety during expectation of phobogenic stimuli is an integral part of abnormal behaviour in phobics. The neural basis of anticipatory anxiety in specific phobia is unknown. Using functional magnetic resonance imaging (fMRI), we explored brain activation in subjects with spider phobia and in non-phobic subjects, while participants anticipated the presentation of either neutral or phobogenic visual stimuli. Subjective ratings indicated that anticipation of phobia-related stimuli was associated with increased anxiety in phobics but not in healthy subjects. FMRI results showed increased activation of the dorsal anterior cingulate cortex (ACC), insula, thalamus, and visual areas in phobics compared to controls during anticipation of phobia-relevant versus anticipation of neutral stimulation. Furthermore, for this contrast, we found also increased activation of the bed nucleus of the stria terminalis (BNST). This particular finding supports models, which propose, based on animal experiments, a critical involvement of the BNST in anticipatory anxiety. Finally, correlation analysis revealed that subjective anxiety of phobics correlated significantly with activation in rostral and dorsal ACC and the anterior medial prefrontal cortex. Thus, activation in different ACC regions and the medial prefrontal cortex seems to be specifically associated with the severity of experienced anticipatory anxiety in subjects with spider phobia.

  6. Vasopressin Innervation of the Mouse (Mus musculus) Brain and Spinal Cord

    PubMed Central

    Rood, Benjamin D.; De Vries, Geert J.

    2014-01-01

    The neuropeptide vasopressin (AVP) has been implicated in the regulation of numerous physiological and behavioral processes. Although mice have become an important model for studying this regulation, there is no comprehensive description of AVP distribution in the mouse brain and spinal cord. With C57BL/6 mice, we used immunohistochemistry to corroborate the location of AVP-containing cells and to define the location of AVP-containing fibers throughout the mouse central nervous system. We describe AVP-immunoreactive (-ir) fibers in midbrain, hindbrain, and spinal cord areas, which have not previously been reported in mice, including innervation of the ventral tegmental area, dorsal and median raphe, lateral and medial parabrachial, solitary, ventrolateral periaqueductal gray, and interfascicular nuclei. We also provide a detailed description of AVP-ir innervation in heterogenous regions such as the amygdala, bed nucleus of the stria terminalis, and ventral forebrain. In general, our results suggest that, compared with other species, the mouse has a particularly robust and widespread distribution of AVP-ir fibers, which, as in other species, originates from a number of different cell groups in the telencephalon and diencephalon. Our data also highlight the robust nature of AVP innervation in specific regulatory nuclei, such as the ventral tegmental area and dorsal raphe nucleus among others, that are implicated in the regulation of many behaviors. PMID:21456024

  7. Effects of juvenile isolation and morphine treatment on social interactions and opioid receptors in adult rats: behavioural and autoradiographic studies.

    PubMed

    Van den Berg, C L; Van Ree, J M; Spruijt, B M; Kitchen, I

    1999-09-01

    The consequences of juvenile isolation and morphine treatment during the isolation period on (social) behaviour and mu-, delta- and kappa-opioid receptors in adulthood were investigated by using a social interaction test and in vitro autoradiography in rats. Juvenile isolation reduced social exploration in adults. Morphine treatment counteracted this reduction in isolated rats, but decreased social exploration in nonisolated rats. Self-grooming and nonsocial exploration were enhanced after juvenile isolation. Morphine treatment had no effect on self-grooming, but suppressed nonsocial exploration in isolated rats. With respect to the opioid receptors, juvenile isolation resulted in regiospecific increases in mu-binding sites with a 58% increase in the basolateral amygdala and a 33% increase in the bed nucleus of stria terminalis. Morphine treatment in isolated rats reversed this upregulation in both areas. The number of delta-binding sites did not differ between the experimental groups. A general upregulation of kappa-binding sites was observed after juvenile isolation, predominantly in the cortical regions, the hippocampus and the substantia nigra. Morphine treatment did not affect the upregulation of kappa-receptors. The results show that juvenile isolation during the play period causes long-term effects on social and nonsocial behaviours and on the number of mu- and kappa- but not delta-opioid receptors in distinct brain areas. The number of mu-receptors in the basolateral amygdala appears to be negatively correlated with the amount of social exploration in adult rats.

  8. Secretagogin is a Ca2+-binding protein identifying prospective extended amygdala neurons in the developing mammalian telencephalon

    PubMed Central

    Mulder, Jan; Spence, Lauren; Tortoriello, Giuseppe; DiNieri, Jennifer A.; Uhlén, Mathias; Shui, Bo; Kotlikoff, Michael I.; Yanagawa, Yuchio; Aujard, Fabienne; Hökfelt, Tomas; Hurd, Yasmin L.; Harkany, Tibor

    2010-01-01

    The Ca2+-binding proteins (CBPs) calbindin D28k, calretinin and parvalbumin are phenotypic markers of functionally diverse subclasses of neurons in the adult brain. The developmental dynamics of CBP expression are precisely timed: calbindin and calretinin are present in prospective cortical interneurons from mid-gestation, while parvalbumin only becomes expressed during the early postnatal period in rodents. Secretagogin (scgn) is a CBP cloned from pancreatic β and neuroendocrine cells. We hypothesized that scgn may be expressed by particular neuronal contingents during prenatal development of the mammalian telencephalon. We find that scgn is expressed in neurons transiting in the subpallial differentiation zone by embryonic day (E) 11 in mouse. From E12, scgn+ cells commute towards the extended amygdala and colonize the bed nucleus of stria terminalis, interstitial nucleus of the posterior limb of the anterior commissure, dorsal substantia innominata (SI), and the central and medial amygdaloid nuclei. Scgn+ neurons can acquire a cholinergic phenotype in the SI or differentiate into GABA cells in the central amygdala. We also uncover phylogenetic differences in scgn expression since this CBP defines not only neurons destined to the extended amygdala but also cholinergic projection cells and cortical pyramidal cells in the fetal non-human primate and human brains, respectively. Overall, our findings emphasize the developmentally shared origins of neurons populating the extended amygdala, and suggest that secretagogin can be relevant to the generation of functional modalities in specific neuronal circuitries. PMID:20529129

  9. Withdrawal-associated increases and decreases in functional neural connectivity associated with altered emotional regulation in alcoholism.

    PubMed

    O'Daly, Owen G; Trick, Leanne; Scaife, Jess; Marshall, Jane; Ball, David; Phillips, Mary L; Williams, Stephen S C; Stephens, David N; Duka, Theodora

    2012-09-01

    Alcoholic patients who have undergone multiple detoxifications/relapses show altered processing of emotional signals. We performed functional magnetic resonance imaging during performance of implicit and explicit versions of a task in which subjects were presented with morphs of fearful facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n=12) or singly detoxified patients (SDTx; n=17), and social drinker controls (n=31). Alcoholic patients were less able than controls to recognize fearful expressions, and showed lower activation in prefrontal areas, including orbitofrontal cortex and insula, which mediate emotional processing. The decrease in activation was greater in MDTx patients who also showed decreased connectivity between insula and prefrontal areas, and between amygdala and globus pallidus. In the explicit condition, the strength of connectivity between insula and areas involved in regulation of emotion (inferior frontal cortex and frontal pole) was negatively correlated with both the number of detoxifications and dependency (measured by the severity of alcohol dependency (SADQ) and control over drinking score (Impaired Control questionnaire, ICQ)). In contrast, increased connectivity was found between insula and the colliculus neuronal cluster, and between amygdala and stria terminalis bed nucleus. In the implicit condition, number of detoxifications and ICQ score correlated positively with connectivity between amygdala and prefrontal cortical areas involved in attentional and executive processes. Repeated episodes of detoxification from alcohol are associated with altered function both in fear perception pathways and in cortical modulation of emotions. Such changes may confer increased sensitivity to emotional stress and impaired social competence, contributing to relapse.

  10. Parabrachial-hypothalamic interactions are required for normal conditioned taste aversions

    PubMed Central

    Dayawansa, Samantha; Ruch, Stacey

    2013-01-01

    Rats with bilateral excitotoxic lesions of the parabrachial nuclei (PBN) fail to acquire a conditioned taste aversion (CTA), yet they retain the ability to express a CTA learned prior to incurring the damage. Rats with bilateral electrolytic lesions of the lateral hypothalamus (LH) also have CTA learning deficits. The PBN have reciprocal neural connections with the LH. This suggests that these CTA deficits may be functionally related. Electrolytic lesions damage fibers of passage, as well as intrinsic neurons. Thus, these LH lesions might also interrupt reciprocal connections between the PBN and other ventral forebrain areas, such as the amygdala and bed nucleus of the stria terminalis. To distinguish the source of the LH-lesion deficit, we tested for CTA first after bilateral excitotoxic lesions of LH and subsequently with a second set of animals that had asymmetric excitotoxic PBN and LH lesions. The rats with bilateral excitotoxic LH lesions showed deficits when acquiring a postlesion CTA. The asymmetrical PBN-LH lesions not only slowed acquisition of a CTA but also sped up extinction. This implies that interaction between the two structures, at minimum, facilitates CTA learning and may have a role in its consolidation. PMID:24259462

  11. The effects of prenatal sex steroid hormones on sexual differentiation of the brain

    PubMed Central

    Karaismailoğlu, Serkan; Erdem, Ayşen

    2013-01-01

    Most of the anatomical, physiological and neurochemical gender-related differences in the brain occur prenatally. The sexual differences in the brain are affected by sex steroid hormones, which play important roles in the differentiation of neuroendocrine system and behavior. Testosterone, estrogen and dihydrotestosterone are the main steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The structural and behavioral differences in the female and male brains are observed in many animal species; however, these differences are variable between species. Animal and human (in vivo imaging and postmortem) studies on sex differences in the brain have shown many differences in the local distribution of the cortex, the gray-white matter ratio, corpus callosum, anterior commissure, hypothalamus, bed nucleus of the stria terminalis, limbic system and neurotransmitter systems. This review aims to evaluate the anatomical, physiological and neurochemical differences in the female and male brains and to assess the effect of prenatal exposure to sex steroid hormones on the developing brain. PMID:24592097

  12. Loss of environmental enrichment increases vulnerability to cocaine addiction.

    PubMed

    Nader, Joëlle; Chauvet, Claudia; Claudia, Chauvet; Rawas, Rana El; Favot, Laure; Jaber, Mohamed; Thiriet, Nathalie; Solinas, Marcello

    2012-06-01

    Life experiences, especially during critical periods of maturation, such as adolescence, can dramatically affect vulnerability to diseases at adulthood. Early exposure to positive environmental conditions such as environmental enrichment (EE) has been shown to reduce the occurrence and the intensity of neurological and psychiatric disorders including drug addiction. However, whether or not exposure to EE during early stages of life would protect from addiction when, at adulthood, individuals may find themselves in non-enriched conditions has not been investigated. Here we show that switching mice from EE to non-enriched standard environments not only results in the loss of the preventive effects of EE but also increases the rewarding effects of cocaine. This enhanced vulnerability is associated with emotional distress and with increased levels in the mRNA levels of corticotropin releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST), as well as with increases in CREB phosphorylation in the BNST and in the shell of the nucleus accumbens. The increased sensitivity to the rewarding effects of cocaine is completely blocked by the CRF antagonist antalarmin, confirming a major role of the CRF system in the negative consequences of this environmental switch. These results indicate that positive life conditions during early stages of life, if they are not maintained at adulthood, may have negative emotional consequences and increase the risks to develop drug addiction.

  13. Comparison of the locomotor activating effects of bicuculline infusions into the preoptic area and ventral pallidum

    PubMed Central

    Zahm, Daniel S.; Schwartz, Zachary M.; Lavezzi, Heather N.; Yetnikoff, Leora; Parsley, Kenneth P.

    2013-01-01

    Ambulatory locomotion in the rodent is robustly activated by unilateral infusions into the basal forebrain of type A gamma-aminobutyric acid (GABAA) receptor antagonists, such as bicuculline and picrotoxin. The present study was carried out to better localize the neuroanatomical substrate(s) underlying this effect. To accomplish this, differences in total locomotion accumulated during a 20 minute test period following bicuculline versus saline infusions in male Sprague-Dawley rats were calculated, rank ordered and mapped on a diagram of basal forebrain transposed from immunoprocessed sections. The most robust locomotor activation was elicited by bicuculline infusions clustered in rostral parts of the preoptic area. Unilateral infusions of bicuculline into the ventral pallidum produced an unanticipatedly diminutive activation of locomotion, which led us to evaluate bilateral ventral pallidal infusions, and these also produced only a small activation of locomotion, and, interestingly, a non-significant trend toward suppression of rearing. Subjects with bicuculline infused bilaterally into the ventral pallidum also exhibited persistent bouts of abnormal movements. Bicuculline infused unilaterally into other forebrain structures, including the bed nucleus of stria terminalis, caudate-putamen, globus pallidus, sublenticular extended amygdala and sublenticular substantia innominata, did not produce significant locomotor activation. Our data identify the rostral preoptic area as the main substrate for the locomotor activating effects of basal forebrain bicuculline infusions. In contrast, slight activation of locomotion and no effect on rearing accompanied unilateral and bilateral ventral pallidal infusions. Implications of these findings for forebrain processing of reward are discussed. PMID:23423460

  14. Song environment affects singing effort and vasotocin immunoreactivity in the forebrain of male Lincoln's sparrows.

    PubMed

    Sewall, Kendra B; Dankoski, Elyse C; Sockman, Keith W

    2010-08-01

    Male songbirds often establish territories and attract mates by singing, and some song features can reflect the singer's condition or quality. The quality of the song environment can change, so male songbirds should benefit from assessing the competitiveness of the song environment and appropriately adjusting their own singing behavior and the neural substrates by which song is controlled. In a wide range of taxa, social modulation of behavior is partly mediated by the arginine vasopressin or vasotocin (AVP/AVT) systems. To examine the modulation of singing behavior in response to the quality of the song environment, we compared the song output of laboratory-housed male Lincoln's sparrows (Melospiza lincolnii) exposed to 1 week of chronic playback of songs categorized as either high or low quality, based on song length, complexity, and trill performance. To explore the neural basis of any facultative shifts in behavior, we also quantified the subjects' AVT immunoreactivity (AVT-IR) in three forebrain regions that regulate sociosexual behavior: the medial bed nucleus of the stria terminalis (BSTm), the lateral septum (LS), and the preoptic area. We found that high-quality songs increased singing effort and reduced AVT-IR in the BSTm and LS, relative to low-quality songs. The effect of the quality of the song environment on both singing effort and forebrain AVT-IR raises the hypothesis that AVT within these brain regions plays a role in the modulation of behavior in response to competition that individual males may assess from the prevailing song environment.

  15. Dissociated functional pathways for appetitive and consummatory reproductive behaviors in male Syrian hamsters.

    PubMed

    Been, Laura E; Petrulis, Aras

    2012-02-01

    In many species, including Syrian hamsters, the generation of male reproductive behavior depends critically on the perception of female odor cues from conspecifics in the environment. The behavioral response to these odors is mediated by a network of steroid-sensitive ventral forebrain nuclei including the medial amygdala (MA), posterior bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA). Previous studies have demonstrated that each of these three nuclei is required for appropriate sexual behavior and that MA preferentially sends female odor information directly to BNST and MPOA. It is unknown, however, how the functional connections between MA and BNST and/or MPOA are organized to generate different aspects of reproductive behavior. Therefore, the following experiments used the asymmetrical pathway lesion technique to test the role of the functional connections between MA and BNST and/or MPOA in odor preference and copulatory behaviors. Lesions that functionally disconnected MA from MPOA eliminated copulatory behavior but did not affect odor preference. In contrast, lesions that functionally disconnected MA from BNST eliminated preference for volatile female odors but did not affect preference for directly contacted odors or copulatory behavior. These results therefore demonstrate a double dissociation in the functional connections required for attraction to volatile sexual odors and copulation and, more broadly, suggest that appetitive and consummatory reproductive behaviors are mediated by distinct neural pathways.

  16. Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model.

    PubMed

    Corre, Christina; Friedel, Miriam; Vousden, Dulcie A; Metcalf, Ariane; Spring, Shoshana; Qiu, Lily R; Lerch, Jason P; Palmert, Mark R

    2016-03-01

    Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.

  17. Brain stress systems in the amygdala and addiction.

    PubMed

    Koob, George F

    2009-10-13

    Dysregulation of the brain emotional systems that mediate arousal and stress is a key component of the pathophysiology of drug addiction. Drug addiction is a chronically relapsing disorder characterized by a compulsion to seek and take drugs and the development of dependence and manifestation of a negative emotional state when the drug is removed. Activation of brain stress systems is hypothesized to be a key element of the negative emotional state produced by dependence that drives drug-seeking through negative reinforcement mechanisms. The focus of the present review is on the role of two key brain arousal/stress systems in the development of dependence. Emphasis is placed on the neuropharmacological actions of corticotropin-releasing factor (CRF) and norepinephrine in extrahypothalamic systems in the extended amygdala, including the central nucleus of the amygdala, bed nucleus of the stria terminalis, and a transition area in the shell of the nucleus accumbens. Compelling evidence argues that these brain stress systems, a heretofore largely neglected component of dependence and addiction, play a key role in engaging the transition to dependence and maintaining dependence once it is initiated. Understanding the role of the brain stress and anti-stress systems in addiction not only provides insight into the neurobiology of the "dark side" of addiction but also provides insight into the organization and function of basic brain emotional circuitry that guides motivated behavior.

  18. Contributions of the paraventricular thalamic nucleus in the regulation of stress, motivation, and mood

    PubMed Central

    Hsu, David T.; Kirouac, Gilbert J.; Zubieta, Jon-Kar; Bhatnagar, Seema

    2014-01-01

    The purpose of this review is to describe how the function and connections of the paraventricular thalamic nucleus (Pa) may play a role in the regulation of stress and negative emotional behavior. Located in the dorsal midline thalamus, the Pa is heavily innervated by serotonin, norepinephrine, dopamine (DA), corticotropin-releasing hormone, and orexins (ORX), and is the only thalamic nucleus connected to the group of structures comprising the amygdala, bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAcc), and infralimbic/subgenual anterior cingulate cortex (sgACC). These neurotransmitter systems and structures are involved in regulating motivation and mood, and display abnormal functioning in several psychiatric disorders including anxiety, substance use, and major depressive disorders (MDD). Furthermore, rodent studies show that the Pa is consistently and potently activated following a variety of stressors and has a unique role in regulating responses to chronic stressors. These observations provide a compelling rationale for investigating the Pa in the link between stress and negative emotional behavior, and for including the Pa in the neural pathways of stress-related psychiatric disorders. PMID:24653686

  19. In vivo magnetic resonance imaging of the human limbic white matter

    PubMed Central

    Mori, Susumu; Aggarwal, Manisha

    2014-01-01

    The limbic system mediates memory, behavior, and emotional output in the human brain, and is implicated in the pathology of Alzheimer’s disease and a wide spectrum of related neurological disorders. In vivo magnetic resonance imaging (MRI) of structural components comprising the limbic system and their interconnections via white matter pathways in the human brain has helped define current understanding of the limbic model based on the classical circuit proposed by Papez. MRI techniques, including diffusion MR imaging, provide a non-invasive method to characterize white matter tracts of the limbic system, and investigate pathological changes that affect these pathways in clinical settings. This review focuses on delineation of the anatomy of major limbic tracts in the human brain, namely, the cingulum, the fornix and fimbria, and the stria terminalis, based on in vivo MRI contrasts. The detailed morphology and intricate trajectories of these pathways that can be identified using relaxometry-based and diffusion-weighted MRI provide an important anatomical reference for evaluation of clinical disorders commonly associated with limbic pathology. PMID:25505883

  20. Autoradiographic localization of (/sup 125/I-Tyr4)bombesin-binding sites in rat brain

    SciTech Connect

    Zarbin, M.A.; Kuhar, M.J.; O'Donohue, T.L.; Wolf, S.S.; Moody, T.W.

    1985-02-01

    The binding of (/sup 125/I-Tyr/sub 4/)bombesin to rat brain slices was investigated. Radiolabeled (Tyr/sub 4/)bombesin bound with high affinity (K/sub d/ . 4 nM) to a single class of sites (B/sub max/ . 130 fmol/mg of protein); the ratio of specific to nonspecific binding was 6/1. Also, pharmacology studies indicated that the C-terminal of bombesin was important for the high affinity binding activity. Autoradiographic studies indicated that the (/sup 125/I-Tyr4)bombesin-binding sites were discretely distributed in certain gray but not white matter regions of rat brain. Highest grain densities were present in the olfactory bulb and tubercle, nucleus accumbens, suprachiasmatic and periventricular nuclei of the hypothalamus, central medial thalamic nucleus, medial amygdaloid nucleus, hippocampus, dentate gyrus, subiculum, nucleus of the solitary tract, and substantia gelatinosa. Moderate grain densities were present in the parietal cortex, deep layers of the neocortex, rhinal cortex, caudate putamen, stria terminalis, locus ceruleus, parabrachial nucleus, and facial nucleus. Low grain densities were present in the globus pallidus, lateral thalamus, and midbrain. Negligible grain densities were present in the cerebellum, corpus callosum, and all regions treated with 1 microM unlabeled bombesin. The discrete regional distribution of binding suggests that endogenous bombesin-like peptides may function as important regulatory agents in certain brain loci.

  1. BNST neurocircuitry in humans

    PubMed Central

    Avery, Suzanne N.; Clauss, Jacqueline A.; Winder, Danny G.; Woodward, Neil; Heckers, Stephan; Blackford, Jennifer Urbano

    2014-01-01

    Anxiety and addiction disorders are two of the most common mental disorders in the United States, and are typically chronic, disabling, and comorbid. Emerging evidence suggests the bed nucleus of the stria terminalis (BNST) mediates both anxiety and addiction through connections with other brain regions, including the amygdala and nucleus accumbens. Although BNST structural connections have been identified in rodents and a limited number of structural connections have been verified in non-human primates, BNST connections have yet to be described in humans. Neuroimaging is a powerful tool for identifying structural and functional circuits in vivo. In this study, we examined BNST structural and functional connectivity in a large sample of humans. The BNST has structural and functional connections with multiple subcortical regions, including limbic, thalamic, and basal ganglia structures, confirming structural findings in rodents. We describe two novel connections in the human brain that have not been previously reported in rodents or non-human primates, including structural connections with the temporal pole, and functional connections with the paracingulate gyrus. The findings of this study provide a map of the BNST’s structural and functional connectivity across brain in healthy humans. In large part, the BNST neurocircuitry in humans is similar to findings from rodents and non-human primates; however, several connections are unique to humans. Future explorations of BNST neurocircuitry in anxiety and addiction disorders have the potential to reveal novel mechanisms underlying these disabling psychiatric illnesses. PMID:24444996

  2. Region-specific testosterone modulation of the vasotocin-immunoreactive system in male dark-eyed junco, Junco hyemalis.

    PubMed

    Plumari, L; Plateroti, S; Deviche, P; Panzica, G C

    2004-02-27

    The nonapeptide vasotocin (VT) is the avian equivalent of the mammalian antidiuretic hormone vasopressin and is believed to control aggressive and reproductive behaviors. Brain VT distribution has been described in several domesticated avian species. We previously demonstrated that VT distribution in the brain of a free-ranging male passerine, the dark-eyed Junco, Junco hyemalis, resembles that in domesticated birds. A preliminary study also suggested that the VT-immunoreactive (VT-ir) system of juncos is regulated by testosterone (T), as is the case of galliforms. To test this hypothesis, we investigated the effects of castration and T replacement on brain VT-ir innervation in adult male juncos. Castration reduced VT-ir innervation in the lateral septum (SL), the medial preoptic nucleus, the nucleus of the stria terminalis and the intercollicularis nucleus. These effects of castration were largely reversed by T treatment at high physiological doses, but significantly so only for the SL. Given the demonstrated behavioral role of the above VT-ir-containing brain regions, the results suggest that these regions may be sites of action of VT on reproductive behaviors.

  3. PACAP in the BNST produces anorexia and weight loss in male and female rats.

    PubMed

    Kocho-Schellenberg, Margaret; Lezak, Kimberly R; Harris, Olivia M; Roelke, Erin; Gick, Niklas; Choi, Inyop; Edwards, Shaquille; Wasserman, Emily; Toufexis, Donna J; Braas, Karen M; May, Victor; Hammack, Sayamwong E

    2014-06-01

    Recent gene association studies have implicated pituitary adenylate cyclase-activating peptide (PACAP) systems in several psychiatric disorders associated with stressor exposure, and we have argued that many of the behavioral consequences of repeated stressor exposure may depend on the expression of PACAP in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of the activation of stress systems can be anorexia and subsequent weight loss, and both the activation of central PACAP systems as well as neuronal activity in the BNST have also been associated with anorexic states in rodents. Hence, we investigated the regulation of food and water intake and weight loss following BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake in the first 24 h following infusion. Because different BNST subregions differentially regulate stress responding, we further examined the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion resulted in weight loss. PACAP38 infused into the lateral ventricles did not alter weight, suggesting that the effects of BNST-infused PACAP were not mediated by leakage into the ventricular system. These data suggest that PACAP receptor activation in posterior BNST subregions can produce anorexia and weight loss, and corroborate growing data implicating central PACAP activation in mediating the consequences of stressor exposure.

  4. Ventral premammillary nucleus as a critical sensory relay to the maternal aggression network

    PubMed Central

    Motta, Simone C.; Guimarães, Cibele Carla; Furigo, Isadora Clivatti; Sukikara, Marcia Harumi; Baldo, Marcus V. C.; Lonstein, Joseph S.; Canteras, Newton S.

    2013-01-01

    Maternal aggression is under the control of a wide variety of factors that prime the females for aggression or trigger the aggressive event. Maternal attacks are triggered by the perception of sensory cues from the intruder, and here we have identified a site in the hypothalamus of lactating rats that is highly responsive to the male intruder—the ventral premammillary nucleus (PMv). The PMv is heavily targeted by the medial amygdalar nucleus, and we used lesion and immediate-early gene studies to test our working hypothesis that the PMv signals the presence of a male intruder and transfers this information to the network organizing maternal aggression. PMv-lesioned dams exhibit significantly reduced maternal aggression, without affecting maternal care. The Fos analysis revealed that PMv influences the activation of hypothalamic and septal sites shown to be mobilized during maternal aggression, including the medial preoptic nucleus (likely to represent an important locus to integrate priming stimuli critical for maternal aggression), the caudal two-thirds of the hypothalamic attack area (comprising the ventrolateral part of the ventromedial hypothalamic nucleus and the adjacent tuberal region of the lateral hypothalamic area, critical for the expression of maternal aggression), and the ventral part of the anterior bed nuclei of the stria terminalis (presently discussed as being involved in controlling neuroendocrine and autonomic responses accompanying maternal aggression). These findings reveal an important role for the PMv in detecting the male intruder and how this nucleus modulates the network controlling maternal aggression. PMID:23918394

  5. The Human BNST: Functional Role in Anxiety and Addiction

    PubMed Central

    Avery, S N; Clauss, J A; Blackford, J U

    2016-01-01

    The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region—the bed nucleus of the stria terminalis (BNST)—in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment. PMID:26105138

  6. Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal.

    PubMed

    Fox, Megan E; Rodeberg, Nathan T; Wightman, R Mark

    2017-02-01

    Dysregulated catecholamine signaling has long been implicated in drug abuse. Although much is known about adaptations following chronic drug administration, little work has investigated how a single drug exposure paired with withdrawal influences catecholamine signaling in vivo. We used fast-scan cyclic voltammetry in freely moving rats to measure real-time catecholamine overflow during acute morphine exposure and naloxone-precipitated withdrawal in two regions associated with the addiction cycle: the dopamine-dense nucleus accumbens (NAc) and norepinephrine-rich ventral bed nucleus of the stria terminalis (vBNST). We compared dopamine transients in the NAc with norepinephrine concentration changes in the vBNST, and correlated release with specific withdrawal-related behaviors. Morphine increased dopamine transients in the NAc, but did not elicit norepinephrine responses in the vBNST. Conversely, dopamine output was decreased during withdrawal, while norepinephrine was released in the vBNST during specific withdrawal symptoms. Both norepinephrine and withdrawal symptoms could be elicited in the absence of morphine by administering naloxone with an α2 antagonist. The data support reciprocal roles for dopamine and norepinephrine signaling during drug exposure and withdrawal. The data also support the allostasis model and show that negative-reinforcement may begin working after a single exposure/withdrawal episode.

  7. Endogenous CNS expression of neurotensin and neurotensin receptors is altered during the postpartum period in outbred mice.

    PubMed

    Driessen, Terri M; Zhao, Changjiu; Whittlinger, Anna; Williams, Horecia; Gammie, Stephen C

    2014-01-01

    Neurotensin (NT) is a neuropeptide identical in mice and humans that is produced and released in many CNS regions associated with maternal behavior. NT has been linked to aspects of maternal care and previous studies have indirectly suggested that endogenous NT signaling is altered in the postpartum period. In the present study, we directly examine whether NT and its receptors exhibit altered gene expression in maternal relative to virgin outbred mice using real time quantitative PCR (qPCR) across multiple brain regions. We also examine NT protein levels using anti-NT antibodies and immunohistochemistry in specific brain regions. In the medial preoptic area (MPOA), which is critical for maternal behaviors, mRNA of NT and NT receptor 3 (Sort1) were significantly up-regulated in postpartum mice compared to virgins. NT mRNA was also elevated in postpartum females in the bed nucleus of the stria terminalis dorsal. However, in the lateral septum, NT mRNA was down-regulated in postpartum females. In the paraventricular nucleus of the hypothalamus (PVN), Ntsr1 expression was down-regulated in postpartum females. Neurotensin receptor 2 (Ntsr2) expression was not altered in any brain region tested. In terms of protein expression, NT immunohistochemistry results indicated that NT labeling was elevated in the postpartum brain in the MPOA, lateral hypothalamus, and two subregions of PVN. Together, these findings indicate that endogenous changes occur in NT and its receptors across multiple brain regions, and these likely support the emergence of some maternal behaviors.

  8. The CRH1 antagonist GSK561679 increases human fear but not anxiety as assessed by startle.

    PubMed

    Grillon, Christian; Hale, Elizabeth; Lieberman, Lynne; Davis, Andrew; Pine, Daniel S; Ernst, Monique

    2015-03-13

    Fear to predictable threat and anxiety to unpredictable threat reflect distinct processes mediated by different brain structures, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), respectively. This study tested the hypothesis that the corticotropin-releasing factor (CRF1) antagonist GSK561679 differentially reduces anxiety but increases fear in humans. A total of 31 healthy females received each of four treatments: placebo, 50 mg GSK561679 (low-GSK), 400 mg GSK561679 (high-GSK), and 1 mg alprazolam in a crossover design. Participants were exposed to three conditions during each of the four treatments. The three conditions included one in which predictable aversive shocks were signaled by a cue, a second during which shocks were administered unpredictably, and a third condition without shock. Fear and anxiety were assessed using the acoustic startle reflex. High-GSK had no effect on startle potentiation during unpredictable threat (anxiety) but increased startle potentiation during the predictable condition (fear). Low-GSK did not affect startle potentiation across conditions. Consistent with previous findings, alprazolam reduced startle potentiation during unpredictable threat but not during predictable threat. The increased fear by high-GSK replicates animal findings and suggests a lift of the inhibitory effect of the BNST on the amygdala by the CRF1 antagonist.

  9. Microstructural White Matter Abnormalities and Cognitive Dysfunction in Subcortical Ischemic Vascular Disease: an Atlas-Based Diffusion Tensor Analysis Study.

    PubMed

    Lin, Lin; Xue, Yunjing; Duan, Qing; Sun, Bin; Lin, Hailong; Chen, Xiaodan; Luo, Ling; Wei, Xiaofan; Zhang, Zhongping

    2015-06-01

    Recent studies in subcortical ischemic vascular disease (SIVD) suggest the involvement of white matter (WM) abnormalities underlying the pathogenesis of cognitive function impairment. Here, we performed magnetic resonance diffusion tensor imaging (DTI) on detecting WM damage and to investigate the correlations between DTI measures and cognitive dysfunction in SIVD patients. Fifty right-handed SIVD patients were recruited and divided into vascular cognitive impairment on dementia (VCIND) group and normal cognition (NC) group. Twenty-two VCIND patients and 28 NC patients underwent DTI scanning and neuropsychological assessment. Atlas-based analysis (ABA) was performed on each subject for extracting FA and MD measures from supratentorial tracts. Among VCIND, as compared to NC patients, decreased FA and increased MD were observed in all projection fibers (bilateral anterior, posterior limb, and retrolenticular part of internal capsule, anterior, superior, and posterior corona radiata and posterior thalamic radiation), association fibers (bilateral sagittal stratum, external capsule, cingulum, fornix, and stria terminalis, superior longitudinal fasciculus, superior fronto-occipital fasciculus, and uncinate fasciculus), and commissural fibers (genu, body, splenium, and bilateral tapetum of corpus callosum). Furthermore, we also found that MoCA scores correlated with DTI values in all supratentorial WM tracts. The results suggested that SIVD patients demonstrated abnormal WM connectivity in all supratentorial regions. Moreover, the severity of damage in WM tracts correlated with cognitive dysfunction.

  10. Cloning and expression of a novel neuropeptide Y receptor.

    PubMed

    Weinberg, D H; Sirinathsinghji, D J; Tan, C P; Shiao, L L; Morin, N; Rigby, M R; Heavens, R H; Rapoport, D R; Bayne, M L; Cascieri, M A; Strader, C D; Linemeyer, D L; MacNeil, D J

    1996-07-12

    The neuropeptide Y family of peptides, which includes neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP), are found in the central and peripheral nervous system and display a wide array of biological activities. These actions are believed to be mediated through pharmacologically distinct G protein-coupled receptors, and, to date, three members of the NPY receptor family have been cloned. In this study we describe the cloning and expression of a novel NPY receptor from mouse genomic DNA. This receptor, designated NPY Y5, shares 60% amino acid identity to the murine NPY Y1 receptor. The pharmacology of this novel receptor resembles that of the NPY Y1 receptor and is distinct from that described for the NPY Y2, Y3, and Y4 receptors. In situ hybridization of mouse brain sections reveals expression of this receptor within discrete regions of the hypothalamus including the suprachiasmatic nucleus, anterior hypothalamus, bed nucleus stria terminalis, and the ventromedial nucleus with no localization apparent elsewhere in the brain.

  11. Chronic social subordination stress modulates glutamic acid decarboxylase (GAD) 67 mRNA expression in central stress circuits

    PubMed Central

    Makinson, Ryan; Lundgren, Kerstin H.; Seroogy, Kim B.; Herman, James P.

    2015-01-01

    Chronic social subordination is a well-known precipitant of numerous psychiatric and physiological health concerns. In this study, we examine the effects of chronic social stress in the visible burrow system (VBS) on the expression of glutamic acid decarboxylase (GAD) 67 and brain-derived neurotropic factor (BDNF) mRNA in forebrain stress circuitry. Male rats in the VBS system form a dominance hierarchy, whereby subordinate males exhibit neuroendocrine and physiological profiles characteristic of chronic exposure to stress. We found that social subordination decreases GAD67 mRNA in the peri-paraventricular nucleus region of the hypothalamus and the interfascicular nucleus of the bed nucleus of the stria terminalis (BNST), and increases in GAD67 mRNA in the hippocampus, medial prefrontal cortex, and dorsal medial hypothalamus. Expression of BDNF mRNA increased in the dorsal region of the BNST, but remained unchanged in all other regions examined. Results from this study indicate that social subordination is associated with several region-specific alterations in GAD67 mRNA expression in central stress circuits, whereas changes in the expression of BDNF mRNA are limited to the BNST. PMID:26066725

  12. Voluntary Exercise Facilitates Pair-Bonding in Male Prairie Voles

    PubMed Central

    Kenkel, William M; Carter, C. Sue

    2015-01-01

    The neuropeptides oxytocin and vasopressin have been implicated in exercise, as well as monogamy and parental behavior. In this study, we compared behavioral and neuroendocrine effects of access to an exercise wheel versus the sedentary state typical in lab animal housing. Male prairie voles (Microtus ochrogaster) were studied because of their extensive repertoire of social behaviors including pair bond formation and biparental care, which are influenced by oxytocin and vasopressin. Subjects in one group had access to a running wheel in their cage (Wheel), and voluntarily ran approximately 1.5 km/day for six weeks; these animals were compared to males in standard housing conditions (n = 10 / group). Males allowed to exercise formed partner preferences significantly faster than controls and exhibited fewer oxytocin neurons, as measured by immunohistochemistry in the bed nucleus of the stria terminalis. We observed no differences in terms of anxiety-related behavior, or alloparental responsiveness. Males with a running wheel equipped cage gained more total body weight, and by the end of the six weeks were found to have less subcutaneous fat and larger testes as a percentage of bodyweight. The changes to gonadal regulation and pair-bonding behavior associated with voluntary exercise are discussed in terms of their possible relevance to the natural history of this species. PMID:26409174

  13. In three brain regions central to maternal behaviour, neither male nor female Phodopus dwarf hamsters show changes in oestrogen receptor alpha distribution with mating or parenthood.

    PubMed

    Timonin, M E; Cushing, B S; Wynne-Edwards, K E

    2008-12-01

    Oestrogen receptor (ER)alpha immunoreactivity in three brain regions relevant to maternal behaviour (medial preoptic area, bed nucleus of the stria terminalis and medial amygdala) was measured in two species of dwarf hamster that both mate during a postpartum oestrous but differ in expression of paternal behaviour. Male and female Phodopus campbelli and Phodopus sungorus were sampled as sexually naive adults, following mating to satiety, and as new parents. In all brain regions, females expressed higher levels of ER alpha than males. Species did not have an effect on ER alpha distribution except in the medial amygdala, where P. sungorus females had higher expression levels than all other groups. Behavioural status was not associated with altered ER alpha expression. These results were not expected for females and suggest that a primary activational role for oestrogen, acting through ER alpha in these regions, does not generalize to maternal behaviour in Phodopus. In males, these results are consistent with previous manipulations of the ER alpha ligand, oestrogen, and suggest that paternal behaviour in P. campbelli is likely to be regulated by developmental effects of oestrogen on the brain during early life (similar to Microtus ochrogaster), rather than through activation by oestrogen at the time of fatherhood (similar to Peromyscus californicus).

  14. Chronic social isolation enhances reproduction in the monogamous prairie vole (Microtus ochrogaster).

    PubMed

    Perry, Adam N; Carter, C Sue; Cushing, Bruce S

    2016-06-01

    Chronic stressors are generally considered to disrupt reproduction and inhibit mating. Here we test the hypothesis that a chronic stressor, specifically social isolation, can facilitate adaptive changes that enhance/accelerate reproductive effort. In general, monogamous species display high levels of prosociality, delayed sexual maturation, and greater parental investment in fewer, higher quality offspring compared with closely related polygynous species. We predicted that chronic social isolation would promote behavioral and neurochemical patterns in prairie voles associated with polygyny. Male and female prairie voles were isolated for four weeks and changes in mating behavior, alloparental care, estrogen receptor (ER) α expression and tyrosine hydroxylase (TH) expression in brain regions regulating sociosexual behavior were examined. In males, isolation accelerated copulation, increased ERα in the medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpm), and reduced TH expression in the MEApd and BSTpm, but had no effect on alloparental behavior. In females, isolation resulted in more rapid estrus induction and reduced TH expression in the MEApd and BSTpm, but had no effect on estradiol sensitivity or ERα expression. The results support the hypothesis that ERα expression in the MEApd and BSTpm is a critical determinant of male copulatory behavior and/or mating system. The lack of change in alloparental behavior suggests that changes in prosocial behavior are selective and regulated by different mechanisms. The results also suggest that TH in the MEApd and BSTpm may play a critical role in determining mating behavior in both sexes.

  15. Effects of postnatal estrogen manipulations on juvenile alloparental behavior.

    PubMed

    Perry, Adam N; Sue Carter, C; Cushing, Bruce S

    2015-09-01

    Sex- and species-specific patterns of estrogen receptor (ER)-α expression are established early in development, which may contribute to sexual differentiation of behavior and determine male social organization. The current study investigated the effects of ERα and ERβ activation during the second postnatal week on subsequent alloparental behavior and ERα expression in juvenile prairie voles. Male and female pups were treated daily with 17β-estradiol (E2, ERα/ERβ agonist), PPT (selective ERα agonist), DPN (selective ERβ agonist), or the oil vehicle on postnatal days (PD) 8-14. Alloparental behavior and ERα expression were examined at PD21. PPT treatment inhibited prosocial motivation in males and increased pup-directed aggression in both sexes. E2 and DPN had no apparent effect on behavior in either sex. PPT-treated males had increased ERα expression in the medial preoptic area (MPN), medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpr). DPN treatment also increased ERα expression in males, but only in the BSTpr. Female ERα expression was unaffected by treatment. These results support the hypothesis that ERα activation in early life is associated with less prosocial patterns of central ERα expression and alloparental behavior in males. The lack of an effect of E2 on behavior suggests that ERβ may antagonize the effects of ERα on alloparental behavior. The results in DPN-treated males suggest that ERα in the MEApd, and not the BSTpr, may be a primary determinant of alloparental behavior in males.

  16. Intraspecific variation in estrogen receptor alpha and the expression of male sociosexual behavior in two populations of prairie voles.

    PubMed

    Cushing, Bruce S; Razzoli, Maria; Murphy, Anne Z; Epperson, Pamela M; Le, Wei-Wei; Hoffman, Gloria E

    2004-08-06

    Estrogen (E) regulates a variety of male sociosexual behaviors. We hypothesize that there is a relationship between the distribution of estrogen receptor alpha (ERalpha) and the degree of male social behavior. To test this hypothesis, ERalpha immunoreactivity (IR) was compared in prairie voles (Microtus ochrogaster) from Illinois (IL), which are highly social, and Kansas (KN), which are less social. The expression of androgen receptors (AR) in males also was compared between populations. The expression of ERalpha and AR were compared in brains from KN and IL males and females using immunocytochemistry (ICC). There were significant intrapopulational differences, with males expressing less ERalpha-IR than females in the medial preoptic area, ventromedial nucleus, ventrolateral portion of the hypothalamus, and bed nucleus of the stria terminalis (BST). IL males also displayed less ERalpha-IR in the medial amygdala (MeA) than IL females. While IL males expressed significantly less ERalpha-IR in the BST and MeA than KN males, there was no difference in AR-IR. Differences in the pattern of ERalpha-IR between KN and IL males were behaviorally relevant, as low levels of testosterone (T) were more effective in restoring sexual activity in castrated KN males than IL males. The lack of difference in AR combined with lower expression of ERalpha-IR in IL males suggests that behavioral differences in response to T are associated with aromatization of T to E and that reduced sensitivity to E may facilitate prosocial behavior in males.

  17. Chemosignals and hormones in the neural control of mammalian sexual behavior.

    PubMed

    Petrulis, Aras

    2013-10-01

    Males and females of most mammalian species depend on chemosignals to find, attract and evaluate mates and, in most cases, these appetitive sexual behaviors are strongly modulated by activational and organizational effects of sex steroids. The neural circuit underlying chemosensory-mediated pre- and peri-copulatory behavior involves the medial amygdala (MA), the bed nucleus of the stria terminalis (BNST), medial preoptic area (MPOA) and ventromedial hypothalamus (VMH), each area being subdivided into interconnected chemoreceptive and hormone-sensitive zones. For males, MA-BNST connections mediate chemoinvestigation whereas the MA-MPOA pathway regulates copulatory initiation. For females, MA-MPOA/BNST connections also control aspects of precopulatory behavior whereas MA-VMH projections control both precopulatory and copulatory behavior. Significant gaps in understanding remain, including the role of VMH in male behavior and MPOA in female appetitive behavior, the function of cortical amygdala, the underlying chemical architecture of this circuit and sex differences in hormonal and neurochemical regulation of precopulatory behavior.

  18. The role of the androgen receptor in CNS masculinization.

    PubMed

    Garcia-Falgueras, Alicia; Pinos, Helena; Collado, Paloma; Pasaro, Eduardo; Fernandez, Rosa; Jordan, Cynthia L; Segovia, Santiago; Guillamon, Antonio

    2005-02-21

    The medial posterior region of the bed nucleus of the stria terminalis (BSTMP) and the locus coeruleus (LC) show opposite patterns of sexual dimorphism. The BSTMP in males is greater in volume and number of neurons than in females (male > female) while in the LC, the opposite is true (female > male). To investigate the possible role of the androgen receptor (AR) in the masculinization of these two structures, males with the testicular feminization mutation (Tfm) were compared to their control littermate males. No differences were seen in the number of neurons of the BSTMP between Tfm and their control littermate males, while in the LC, Tfm males have a greater number of neurons than their control littermate males. These results show that the AR is involved in the control of neuron number in the LC but not in the BSTMP. Results based on the LC suggest that when females have a larger brain area than males, masculinization in males may be achieved through the AR, with androgens perhaps decreasing cell survival.

  19. The expression of brain sexual dimorphism in artificial selection of rat strains.

    PubMed

    Garcia-Falgueras, Alicia; Pinos, Helena; Collado, Paloma; Pasaro, Eduardo; Fernandez, Rosa; Segovia, Santiago; Guillamon, Antonio

    2005-08-09

    Central nervous system sex differences have two morphological patterns. In one pattern, males show larger measurements (volume, number of neurons) than females (male > female; m > f) and, in the other, the opposite is true (female > male; f > m). The bed nucleus of the stria terminalis (BST) is a unique model for the study of sex differences because it has dimorphic and isomorphic subdivisions, with the former showing the two sexually differentiated morphological patterns. Meanwhile, other CNS structures, like the locus coeruleus (LC), present the f > m pattern. The philogenetic maintenance of the two patterns of sexual differentiation can help to disentangle the functional meaning of sex differences. Laboratory rat strains, whether albino or pigmented, descend from the Wistar strain through artificial selection. The present work compares the BST and LC of Wistar and Long-Evans rats. The medial posterior subdivision of the BST (BSTMP) is sexually dimorphic (m > f pattern) in the original (Wistar) and derived (Long-Evans) strains, while the lateral anterior and medial anterior subdivisions of the BST and the LC only present sex differences (f > m pattern) in the ancestor Wistar strain. Isomorphic BST regions are the same in both strains. The fact that the BSTMP, which is implicated in male copulatory behavior, is sexually dimorphic in both strains, as well as in other species, including humans, indicates the relevance of this structure in male sexual behavior in mammals.

  20. KiSS-1 expression and metastin-like immunoreactivity in the rat brain.

    PubMed

    Brailoiu, G Cristina; Dun, Siok L; Ohsawa, Masahiro; Yin, Deling; Yang, Jun; Chang, Jaw Kang; Brailoiu, Eugen; Dun, Nae J

    2005-01-17

    Metastin, the gene product of metastasis suppressor gene KiSS-1, is the endogenous ligand for the G-protein-coupled receptor GPR54 (or AXOR12, or OT7T175). The expression of KiSS-1 gene and peptide and the distribution of metastin were studied in the rat central nervous system by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical methods. KiSS-1 gene and peptide expression was higher in the hypothalamus than in the brainstem and spinal cord. In the brain, metastin-like immunoreactivity (irMT) was found mainly in three groups of cells: dorsomedial hypothalamic nucleus, nucleus of the solitary tract, and caudal ventrolateral medulla. Immunoreactive fibers of varying density were noted in bed nucleus of stria terminalis, septal nuclei, nucleus accumbens, caudate putamen, diagonal band, amygdala, hypothalamus, zona incerta, thalamus, periaqueductal gray, raphe nuclei, lateral parabrachial nucleus, locus coeruleus, spinal trigeminal tract, rostral ventrolateral medulla, and medullary reticular nucleus. Preabsorption of the antiserum with metastin peptide fragment (45-54)-NH2 (1 microg/ml) resulted in no staining in any of the sections. The biological activity of metastin was assessed by monitoring intracellular calcium [Ca2+]i in cultured hippocampal neurons, which are known to express GPR54. Metastin increased [Ca2+]i in a population of cultured hippocampal neurons. The results show that metastin is biologically active in rat central neurons, and its anatomical distribution suggests a possible role in nociception and autonomic and neuroendocrine functions.

  1. Distribution of vasopressin in the forebrain of spotted hyenas.

    PubMed

    Rosen, Greta J; De Vries, Geert J; Villalba, Constanza; Weldele, Mary L; Place, Ned J; Coscia, Elizabeth M; Glickman, Steve E; Forger, Nancy G

    2006-09-01

    The extreme virilization of the female spotted hyena raises interesting questions with respect to sexual differentiation of the brain and behavior. Females are larger and more aggressive than adult, non-natal males and dominate them in social encounters; their external genitalia also are highly masculinized. In many vertebrates, the arginine vasopressin (VP) innervation of the forebrain, particularly that of the lateral septum, is associated with social behaviors such as aggression and dominance. Here, we used immunohistochemistry to examine the distribution of VP cells and fibers in the forebrains of adult spotted hyenas. We find the expected densely staining VP immunoreactive (VP-ir) neurons in the paraventricular and supraoptic nuclei, as well as an unusually extensive distribution of magnocelluar VP-ir neurons in accessory regions. A small number of VP-ir cell bodies are present in the suprachiasmatic nucleus and bed nucleus of the stria terminalis; however, there are extensive VP-ir fiber networks in presumed projection areas of these nuclei, for example, the subparaventricular zone and lateral septum, respectively. No significant sex differences were detected in the density of VP-ir fibers in any area examined. In the lateral septum, however, marked variability was observed. Intact females exhibited a dense fiber network, as did two of the four males examined; the two other males had almost no VP-ir septal fibers. This contrasts with findings in many other vertebrate species, in which VP innervation of the lateral septum is consistently greater in males than in females.

  2. Neuroimaging the temporal dynamics of human avoidance to sustained threat.

    PubMed

    Schlund, Michael W; Hudgins, Caleb D; Magee, Sandy; Dymond, Simon

    2013-11-15

    Many forms of human psychopathology are characterized by sustained negative emotional responses to threat and chronic behavioral avoidance, implicating avoidance as a potential transdiagnostic factor. Evidence from both nonhuman neurophysiological and human neuroimaging studies suggests a distributed frontal-limbic-striatal brain network supports avoidance. However, our understanding of the temporal dynamics of the network to sustained threat that prompts sustained avoidance is limited. To address this issue, 17 adults were given extensive training on a modified free-operant avoidance task in which button pressing avoided money loss during a sustained threat period. Subsequently, subjects underwent functional magnetic resonance imaging while completing the avoidance task. In our regions of interest, we observed phasic, rather than sustained, activation during sustained threat in dorsolateral and inferior frontal regions, anterior and dorsal cingulate, ventral striatum and regions associated with emotion, including the amygdala, insula, substantia nigra and bed nucleus of the stria terminalis complex. Moreover, trait levels of experiential avoidance were negatively correlated with insula, hippocampal and amygdala activation. These findings suggest knowledge that one can consistently avoid aversive outcomes is not associated with decreased threat-related responses and that individuals with greater experiential avoidance exhibit reduced reactivity to initial threat. Implications for understanding brain mechanisms supporting human avoidance and psychological theories of avoidance are discussed.

  3. Jet-Induced Star Formation

    SciTech Connect

    van Breugel, W; Fragile, C; Anninos, P; Murray, S

    2003-12-16

    Jets from radio galaxies can have dramatic effects on the medium through which they propagate. We review observational evidence for jet-induced star formation in low ('FR-I') and high ('FR-II') luminosity radio galaxies, at low and high redshifts respectively. We then discuss numerical simulations which are aimed to explain a jet-induced starburst ('Minkowski's Object') in the nearby FR-I type radio galaxy NGC 541. We conclude that jets can induce star formation in moderately dense (10 cm{sup -3}), warm (10{sup 4} K) gas; that this may be more common in the dense environments of forming, active galaxies; and that this may provide a mechanism for 'positive' feedback from AGN in the galaxy formation process.

  4. Persistent nicorandil induced oral ulceration

    PubMed Central

    Healy, C M; Smyth, Y; Flint, S R

    2004-01-01

    Four patients with nicorandil induced ulceration are described, and the literature on the subject is reviewed. Nicorandil induced ulcers are very painful and distressing for patients. Clinically they appear as large, deep, persistent ulcers that have punched out edges. They are poorly responsive to topical steroids and usually require alteration of nicorandil treatment. The ulceration tends to occur at high doses of nicorandil and all four cases reported here were on doses of 40 mg per day or greater. In these situations reduction of nicorandil dose may be sufficient to promote ulcer healing and prevent further recurrence. However, nicorandil induced ulcers have been reported at doses as low as 10 mg daily and complete cessation of nicorandil may be required. PMID:15201264

  5. Validating induced seismicity forecast models—Induced Seismicity Test Bench

    NASA Astrophysics Data System (ADS)

    Király-Proag, Eszter; Zechar, J. Douglas; Gischig, Valentin; Wiemer, Stefan; Karvounis, Dimitrios; Doetsch, Joseph

    2016-08-01

    Induced earthquakes often accompany fluid injection, and the seismic hazard they pose threatens various underground engineering projects. Models to monitor and control induced seismic hazard with traffic light systems should be probabilistic, forward-looking, and updated as new data arrive. In this study, we propose an Induced Seismicity Test Bench to test and rank such models; this test bench can be used for model development, model selection, and ensemble model building. We apply the test bench to data from the Basel 2006 and Soultz-sous-Forêts 2004 geothermal stimulation projects, and we assess forecasts from two models: Shapiro and Smoothed Seismicity (SaSS) and Hydraulics and Seismics (HySei). These models incorporate a different mix of physics-based elements and stochastic representation of the induced sequences. Our results show that neither model is fully superior to the other. Generally, HySei forecasts the seismicity rate better after shut-in but is only mediocre at forecasting the spatial distribution. On the other hand, SaSS forecasts the spatial distribution better and gives better seismicity rate estimates before shut-in. The shut-in phase is a difficult moment for both models in both reservoirs: the models tend to underpredict the seismicity rate around, and shortly after, shut-in.

  6. Diapir-Induced Reorientation of Enceladus

    NASA Technical Reports Server (NTRS)

    Pappalardo, Robert T.; Nimno, Francis

    2006-01-01

    A viewgraph presentation on the diapir-induced reorientation of Enceladus is shown. The contents include: 1) Activity on Enceladus; 2) Miranda's Coronae: Origin above Diapirs; 3) Reorientation of Miranda; 4) Planetary Reorientation; 5) Modeling Diapir-Induced Reorientation; 6) Diapir-Induced Reorientation: Results; 7) Tectonic Implications of Reorientation; 8) Additional Tests of Reorientation; 9) Diapir-Induced Reorientation of Enceladus: Conclusions; and 10) Diapir-Induced Reorientation: Future Work

  7. Plasma rotation induced by RF

    SciTech Connect

    Chan, V. S.; Chiu, S. C.; Lin-Liu, Y. R. [General Atomics, P.O. Box 85608, San Diego, California 92186-5698; Omelchenko, Y. A. [General Atomics, P.O. Box 85608, San Diego, California 92186-5698

    1999-09-20

    Plasma rotation has many beneficial effects on tokamak operation including stabilization of MHD and microturbulence to improve the beta limit and confinement. Contrary to present-day tokamaks, neutral beams may not be effective in driving rotation in fusion reactors; hence the investigation of radiofrequency (RF) induced plasma rotation is of great interest and potential importance. This paper reviews the experimental results of RF induced rotation and possible physical mechanisms, suggested by theories, to explain the observations. This subject is only in the infancy of its research and many challenging issues remained to be understood and resolved. (c) 1999 American Institute of Physics.

  8. Induced radioactivity in LDEF components

    NASA Technical Reports Server (NTRS)

    Harmon, B. A.; Fishman, G. J.; Parnell, T. A.; Laird, C. E.

    1992-01-01

    A systematic study of the induced radioactivity of the Long Duration Exposure Facility (LDEF) is being carried out in order to gather information about the low earth orbit radiation environment and its effects on materials. The large mass of the LDEF spacecraft, its stabilized configuration, and long mission duration have presented an opportunity to determine space radiation-induced radioactivities with a precision not possible before. Data presented include preliminary activities for steel and aluminum structural samples, and activation subexperiment foils. Effects seen in the data show a clear indication of the trapped proton anisotropy in the South Atlantic Anomaly and suggest contributions from different sources of external radiation fluxes.

  9. Graphene with geometrically induced vorticity.

    PubMed

    Pachos, Jiannis K; Stone, Michael; Temme, Kristan

    2008-04-18

    At half filling, the electronic structure of graphene can be modeled by a pair of free two-dimensional Dirac fermions. We explicitly demonstrate that in the presence of a geometrically induced gauge field an everywhere-real Kekulé modulation of the hopping matrix elements can correspond to a nonreal Higgs field with nontrivial vorticity. This provides a natural setting for fractionally charged vortices with localized zero modes. For fullerenelike molecules we employ the index theorem to demonstrate the existence of six low-lying states that do not depend strongly on the Kekulé-induced mass gap.

  10. Efavirenz-induced exfoliative dermatitis.

    PubMed

    Zhang, Jiu-Cong; Sun, Yong-Tao

    2013-01-01

    Individuals with a human immunodeficiency virus (HIV) infection are at higher risk of developing adverse drug reactions. Multiple drugs are usually prescribed to patients with HIV infection for preventing the replication of HIV and for the treatment of the associated opportunistic infections. We report here the first case of an HIV-1-infected patient who developed an exfoliative dermatitis induced by efavirenz, a non-nucleoside reverse transcriptase inhibitor. Physicians should be aware of the possible occurrence of efavirenz-induced skin eruptions from the start of antiviral treatment of HIV infection.

  11. Method for induced polarization logging

    SciTech Connect

    Vinegar, H.J.; Waxman, M.H.

    1987-04-14

    A method is described for generating a log of the formation phase shift, resistivity and spontaneous potential of an earth formation from data obtained from the earth formation with a multi-electrode induced polarization logging tool. The method comprises obtaining data samples from the formation at measurement points equally spaced in time of the magnitude and phase of the induced voltage and the magnitude and phase of the current supplied by a circuit through a reference resistance R/sub 0/ to a survey current electrode associated with the tool.

  12. An induced junction photovoltaic cell

    NASA Technical Reports Server (NTRS)

    Call, R. L.

    1974-01-01

    Silicon solar cells operating with induced junctions rather than diffused junctions have been fabricated and tested. Induced junctions were created by forming an inversion layer near the surface of the silicon by supplying a sheet of positive charge above the surface. Measurements of the response of the inversion layer cell to light of different wavelengths indicated it to be more sensitive to the shorter wavelengths of the sun's spectrum than conventional cells. The greater sensitivity occurs because of the shallow junction and the strong electric field at the surface.

  13. Conflict-Induced Perceptual Filtering

    ERIC Educational Resources Information Center

    Wendt, Mike; Luna-Rodriguez, Aquiles; Jacobsen, Thomas

    2012-01-01

    In a variety of conflict paradigms, target and distractor stimuli are defined in terms of perceptual features. Interference evoked by distractor stimuli tends to be reduced when the ratio of congruent to incongruent trials is decreased, suggesting conflict-induced perceptual filtering (i.e., adjusting the processing weights assigned to stimuli…

  14. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  15. Oxaliplatin-induced lung fibrosis

    PubMed Central

    Shah, Arpan; Udwadia, Zarir F.; Almel, Sachin

    2009-01-01

    Oxaliplatin has been approved for use as an adjuvant treatment in stage III colorectal carcinoma by the US-FDA. The majority of toxicity caused by this drug is manageable. However, rare, isolated cases of pulmonary fibrosis induced by this drug have been reported in literature. We report one such case of rapidly evolving pulmonary fibrosis following treatment with oxaliplatin. PMID:20838550

  16. Radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Kronenberg, A.

    1994-01-01

    Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.

  17. Adrafinil-induced orofacial dyskinesia.

    PubMed

    Thobois, Stéphane; Xie, Jing; Mollion, Helena; Benatru, Isabelle; Broussolle, Emmanuel

    2004-08-01

    We describe the first case of orofacial abnormal movements induced by adrafinil, a vigilance promoting agent of the same pharmacological class as modafinil. The dyskinesias did not spontaneously recover despite adrafinil withdrawal for a 4-month period. They were secondly dramatically improved by tetrabenazine, a presynaptic dopaminergic depleting drug which was introduced after the 4-month adrafinil-free period.

  18. Adolescents and Exercise Induced Asthma

    ERIC Educational Resources Information Center

    Hansen, Pamela; Bickanse, Shanna; Bogenreif, Mike; VanSickle, Kyle

    2008-01-01

    This article defines asthma and exercise induced asthma, and provides information on the triggers, signs, and symptoms of an attack. It also gives treatments for these conditions, along with prevention guidelines on how to handle an attack in the classroom or on the practice field. (Contains 2 tables and 1 figure.)

  19. [Readers' position against induced abortion].

    PubMed

    1981-08-25

    Replies to the request by the Journal of Nursing on readers' positions against induced abortion indicate there is a definite personal position against induced abortion and the assistance in this procedure. Some writers expressed an emotional "no" against induced abortion. Many quoted arguments from the literature, such as a medical dictionary definition as "a premeditated criminally induced abortion." The largest group of writers quoted from the Bible, the tenor always being: "God made man, he made us with his hands; we have no right to make the decision." People with other philosophies also objected. Theosophical viewpoint considers reincarnation and the law of cause and effect (karma). This philosophy holds that induced abortion impedes the appearance of a reincarnated being. The fundamental question in the abortion problem is, "can the fetus be considered a human life?" The German anatomist Professor E. Bleckschmidt points out that from conception there is human life, hence the fertilized cell can only develop into a human being and is not merely a piece of tissue. Professional nursing interpretation is that nursing action directed towards killing of a human being (unborn child) is against the nature and the essence of the nursing profession. A different opinion states that a nurse cares for patients who have decided for the operation. The nurse doesn't judge but respects the individual's decision. Some proabortion viewpoints considered the endangering of the mother's life by the unborn child, and the case of rape. With the arguments against abortion the question arises how to help the woman with unwanted pregnancy. Psychological counseling is emphasized as well as responsible and careful assistance. Referral to the Society for Protection of the Unborn Child (VBOK) is considered as well as other agencies. Further reader comments on this subject are solicited.

  20. An inducible offense: carnivore morph tadpoles induced by tadpole carnivory

    PubMed Central

    Levis, Nicholas A; de la Serna Buzón, Sofia; Pfennig, David W

    2015-01-01

    Phenotypic plasticity is commonplace, and plasticity theory predicts that organisms should often evolve mechanisms to detect and respond to environmental cues that accurately predict future environmental conditions. Here, we test this prediction in tadpoles of spadefoot toads, Spea multiplicata. These tadpoles develop into either an omnivore ecomorph, which is a dietary generalist, or a carnivore ecomorph, which specializes on anostracan shrimp and other tadpoles. We investigated a novel proximate cue – ingestion of Scaphiopus tadpoles – and its propensity to produce carnivores by rearing tadpoles on different diets. We found that diets containing tadpoles from the genus Scaphiopus produced more carnivores than diets without Scaphiopus tadpoles. We discuss why Scaphiopus tadpoles are an excellent food source and why it is therefore advantageous for S. multiplicata tadpoles to produce an inducible offense that allows them to better utilize this resource. In general, such inducible offenses provide an excellent setting for investigating the proximate and evolutionary basis of phenotypic plasticity. PMID:25897380

  1. Diuretic-induced hypokalaemia inducing torsades de pointes.

    PubMed

    Chvilicek, J P; Hurlbert, B J; Hill, G E

    1995-12-01

    Torsades de pointes (TP), an unique polymorphous type of ventricular tachycardia, is associated with either an acquired or congenitally prolonged QT interval. Several reports have demonstrated TP to follow an acquired prolonged QT interval secondary to chronic hypocalcaemia, hypomagnesaemia, or hypokalaemia. We report a rapid onset, acute extracellular hypokalaemia not associated with other electrolyte disturbances inducing a prolonged QT interval followed by TP. This is the first case report of a rapid onset isolated acute extracellular hypokalaemia inducing TP. Since anaesthetists are involved in therapies that will rapidly reduce extracellular potassium (diuretic, catecholamine, and/or insulin administration, hyperventilation), this cae report serves as a warning that such therapy may have the risk of arrhythmia induction.

  2. Distinguishing warming-induced drought from drought-induced warming

    NASA Astrophysics Data System (ADS)

    Roderick, M. L.; Yin, D.

    2015-12-01

    It is usually observed that temperatures, especially maximum temperatures are higher during drought. A very widely held public perception is that the increase in temperature is a cause of drought. This represents the warming-induced drought scenario. However, the agricultural and hydrologic scientific communities have a very different interpretation with drought being the cause of increasing temperature. In essence, those communities assume the warming is a surface feedback and their interpretation is for drought-induced warming. This is a classic cause-effect problem that has resisted definitive explanation due to the lack of radiative observations at suitable spatial and temporal scales. In this presentation we first summarise the observations and then use theory to untangle the cause-effect relationships that underlie the competing interpretations. We then show how satellite data (CERES, NASA) can be used to disentangle the cause-effect relations.

  3. Does a parthenogenesis-inducing Wolbachia induce vestigial cytoplasmic incompatibility?

    NASA Astrophysics Data System (ADS)

    Kraaijeveld, Ken; Reumer, Barbara M.; Mouton, Laurence; Kremer, Natacha; Vavre, Fabrice; van Alphen, Jacques J. M.

    2011-03-01

    Wolbachia is a maternally inherited bacterium that manipulates the reproduction of its host. Recent studies have shown that male-killing strains can induce cytoplasmic incompatibility (CI) when introgressed into a resistant host. Phylogenetic studies suggest that transitions between CI and other Wolbachia phenotypes have also occurred frequently, raising the possibility that latent CI may be widespread among Wolbachia. Here, we investigate whether a parthenogenesis-inducing Wolbachia strain can also induce CI. Parthenogenetic females of the parasitoid wasp Asobara japonica regularly produce a small number of males that may be either infected or not. Uninfected males were further obtained through removal of the Wolbachia using antibiotics and from a naturally uninfected strain. Uninfected females that had mated with infected males produced a slightly, but significantly more male-biased sex ratio than uninfected females that had mated with uninfected males. This effect was strongest in females that mated with males that had a relatively high Wolbachia titer. Quantitative PCR indicated that infected males did not show higher ratios of nuclear versus mitochondrial DNA content. Wolbachia therefore does not cause diploidization of cells in infected males. While these results are consistent with CI, other alternatives such as production of abnormal sperm by infected males cannot be completely ruled out. Overall, the effect was very small (9%), suggesting that if CI is involved it may have degenerated through the accumulation of mutations.

  4. Fluid injection and induced seismicity

    NASA Astrophysics Data System (ADS)

    Kendall, Michael; Verdon, James

    2016-04-01

    The link between fluid injection, or extraction, and induced seismicity has been observed in reservoirs for many decades. In fact spatial mapping of low magnitude events is routinely used to estimate a stimulated reservoir volume. However, the link between subsurface fluid injection and larger felt seismicity is less clear and has attracted recent interest with a dramatic increase in earthquakes associated with the disposal of oilfield waste fluids. In a few cases, hydraulic fracturing has also been linked to induced seismicity. Much can be learned from past case-studies of induced seismicity so that we can better understand the risks posed. Here we examine 12 case examples and consider in particular controls on maximum event size, lateral event distributions, and event depths. Our results suggest that injection volume is a better control on maximum magnitude than past, natural seismicity in a region. This might, however, simply reflect the lack of baseline monitoring and/or long-term seismic records in certain regions. To address this in the UK, the British Geological Survey is leading the deployment of monitoring arrays in prospective shale gas areas in Lancashire and Yorkshire. In most cases, seismicity is generally located in close vicinity to the injection site. However, in some cases, the nearest events are up to 5km from the injection point. This gives an indication of the minimum radius of influence of such fluid injection projects. The most distant events are never more than 20km from the injection point, perhaps implying a maximum radius of influence. Some events are located in the target reservoir, but most occur below the injection depth. In fact, most events lie in the crystalline basement underlying the sedimentary rocks. This suggests that induced seismicity may not pose a leakage risk for fluid migration back to the surface, as it does not impact caprock integrity. A useful application for microseismic data is to try and forecast induced seismicity

  5. Toxin-induced hepatic injury.

    PubMed

    Lopez, Annette M; Hendrickson, Robert G

    2014-02-01

    Toxins such as pharmaceuticals, herbals, foods, and supplements may lead to hepatic damage. This damage may range from nonspecific symptoms in the setting of liver test abnormalities to acute hepatic failure. The majority of severe cases of toxin-induced hepatic injury are caused by acetaminophen and ethanol. The most important step in the patient evaluation is to gather an extensive history that includes toxin exposure and exclude common causes of liver dysfunction. Patients whose hepatic dysfunction progresses to acute liver failure may benefit from transfer to a transplant service for further management. Currently, the mainstay in management for most exposures is discontinuing the offending agent. This manuscript will review the incidence, pathophysiology, diagnosis and management of the different forms of toxin-induced hepatic injury and exam in-depth the most common hepatic toxins.

  6. Disorder induced Floquet Topological Insulators

    NASA Astrophysics Data System (ADS)

    Bhattacharjee, Paraj; Lindner, Netanel; Rechtsman, Mikael; Refael, Gil

    2014-03-01

    We investigate the possibility of realizing a disorder induced topological state in two dimensional periodically driven systems. This phenomenon is akin to the topological Anderson insulator (TAI) in equilibrium systems. We focus on graphene band structures, where in the presence of the driving electromagnetic field, but in the absence of disorder, the system starts off in a trivial state due to the presence of a sublattice potential. We show that by adding on-site disorder a topological state is induced in this system. We numerically compute the average Bott index (the analog of the Chern number for disordered systems) to show that starting from a trivial phase, topological behavior can be observed at finite disorder strength. In the topological phase, we detect chiral edge states by a numerical time evolution of wavepackets at the edge of the system. We propose an experimental set-up in photonic lattices to observe this phenomenon.

  7. Aloe-induced Toxic Hepatitis

    PubMed Central

    Yang, Ha Na; Kim, Young Mook; Kim, Byoung Ho; Sohn, Kyoung Min; Choi, Myung Jin; Choi, Young Hee

    2010-01-01

    Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity. PMID:20191055

  8. Drug-induced Liver Injury

    PubMed Central

    David, Stefan; Hamilton, James P

    2011-01-01

    Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. PMID:21874146

  9. Abacavir-induced liver toxicity.

    PubMed

    Pezzani, Maria Diletta; Resnati, Chiara; Di Cristo, Valentina; Riva, Agostino; Gervasoni, Cristina

    2016-01-01

    Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine.

  10. Cadmium-induced testicular injury

    SciTech Connect

    Siu, Erica R.; Mruk, Dolores D.; Porto, Catarina S.; Cheng, C. Yan

    2009-08-01

    Cadmium (Cd) is an environmental toxicant and an endocrine disruptor in humans and rodents. Several organs (e.g., kidney, liver) are affected by Cd and recent studies have illustrated that the testis is exceedingly sensitive to Cd toxicity. More important, Cd and other toxicants, such as heavy metals (e.g., lead, mercury) and estrogenic-based compounds (e.g., bisphenols) may account for the recent declining fertility in men among developed countries by reducing sperm count and testis function. In this review, we critically discuss recent data in the field that have demonstrated the Cd-induced toxicity to the testis is probably the result of interactions of a complex network of causes. This is likely to involve the disruption of the blood-testis barrier (BTB) via specific signal transduction pathways and signaling molecules, such as p38 mitogen-activated protein kinase (MAPK). We also summarize current studies on factors that confer and/or regulate the testis sensitivity to Cd, such as Cd transporters and metallothioneins, the impact of Cd on the testis as an endocrine disruptor and oxidative stress inducer, and how it may disrupt the Zn{sup 2+} and/or Ca{sup 2+} mediated cellular events. While much work is needed before a unified mechanistic pathway of Cd-induced testicular toxicity emerges, recent studies have helped to identify some of the likely mechanisms and/or events that take place during Cd-induced testis injury. Furthermore, some of the recent studies have shed lights on potential therapeutic or preventive approaches that can be developed in future studies by blocking or minimizing the destructive effects of Cd to testicular function in men.

  11. The fluctuation induced Hall effect

    SciTech Connect

    Shen, W.; Prager, S.C.

    1993-02-01

    The fluctuation induced Hall term, {le}{approximately}{ovr J} {times} {approximately}{ovr B}{ge}, has been measured in the MST reversed field pinch. The term is of interest as a possible source of current self-generation (dynamo). It is found to be non-negligible, but small in that it can account for less than 25% of the dynamo driven current.

  12. The fluctuation induced Hall effect

    SciTech Connect

    Shen, W.; Prager, S.C.

    1993-02-01

    The fluctuation induced Hall term, [le][approximately][ovr J] [times] [approximately][ovr B][ge], has been measured in the MST reversed field pinch. The term is of interest as a possible source of current self-generation (dynamo). It is found to be non-negligible, but small in that it can account for less than 25% of the dynamo driven current.

  13. Etanercept-induced cystic acne.

    PubMed

    Kashat, Maria; Caretti, Katherine; Kado, Jessica

    2014-07-01

    Tumor necrosis factor α antagonists are potent biologics used to treat a variety of autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn disease, psoriasis, and psoriatic arthritis. These medications are known to have many side effects (eg, infusion reactions, cytopenia, risk for infection, heart failure); however, only a few cases of acne vulgaris have been associated with the use of these biologics, particularly infliximab and adalimumab. We report a rare case of etanercept-induced cystic acne.

  14. Nanostructure-induced DNA condensation

    NASA Astrophysics Data System (ADS)

    Zhou, Ting; Llizo, Axel; Wang, Chen; Xu, Guiying; Yang, Yanlian

    2013-08-01

    The control of the DNA condensation process is essential for compaction of DNA in chromatin, as well as for biological applications such as nonviral gene therapy. This review endeavours to reflect the progress of investigations on DNA condensation effects of nanostructure-based condensing agents (such as nanoparticles, nanotubes, cationic polymer and peptide agents) observed by using atomic force microscopy (AFM) and other techniques. The environmental effects on structural characteristics of nanostructure-induced DNA condensates are also discussed.

  15. Cadmium-induced Testicular Injury*

    PubMed Central

    Siu, Erica R.; Mruk, Dolores D.; Porto, Catarina S.; Cheng, C. Yan

    2009-01-01

    Cadmium (Cd) is an environmental toxicant and an endocrine disruptor in humans. Several organs (e.g., kidney, liver) are affected by Cd and recent studies have illustrated that the testis is exceedingly sensitive to Cd toxicity. More important, Cd and other toxicants, such as heavy metals (e.g., lead, mercury) and estrogenic-based compounds (e.g., bisphenols) may account for the recent declining fertility in men among developed countries by reducing sperm count and testis function. In this review, we critically discuss recent data in the field that have demonstrated the Cd-induced toxicity to the testis is probably the result of interactions of a complex network of causes. This is likely to involve the disruption of the blood-testis barrier (BTB) via specific signal transduction pathways and signaling molecules, such as p38 mitogen-activated protein kinase (MAPK). We also summarize current studies on factors that confer the testis sensitivity to Cd, such as Cd transporters and metallothioneins, and the impact of Cd on the testis as an endocrine disruptor, oxidative stress inducer and how it may disrupt the Zn+2 and/or Ca+2 mediated cellular events. While much work is needed before a unified mechanistic pathway of Cd-induced testicular toxicity is emerged, recent studies have helped to identify some of the likely mechanisms and/or events that take place during Cd-induced testis injury. Furthermore, some of the recent studies have shed lights on potential therapeutic or preventive approaches that can be developed in future studies by blocking or minimizing the destructive effects of Cd to testicular function in men. PMID:19236889

  16. Propulsion Induced Effects Test Program

    NASA Technical Reports Server (NTRS)

    Cappuccio, Gelsomina; Won, Mark; Bencze, Dan

    1999-01-01

    The objective of this milestone is to assess the propulsion/airframe integration characteristics of the Technology Concept Airplane and design variations through computational analysis and experimental subsonic through supersonic wind tunnel testing. The Milestone will generate a comprehensive CFD and wind tunnel data base of the baseline, and design variations. Emphasis will be placed on establishing the propulsion induced effects on the flight performance of the Technology Concept Airplane with all appropriate wind tunnel corrections.

  17. Acyclovir-induced thrombotic microangiopathy

    PubMed Central

    Goli, R.; Mukku, K. K.; Devaraju, S. B. R.; Uppin, M. S.

    2017-01-01

    Acyclovir is a commonly used antiviral drug. Acute kidney injury (AKI) due to intratubular crystal precipitation and interstitial nephritis is well known. Here we present a case of acyclovir induced AKI in a 61 year old male with herpes zoster, which presented like thrombotic microangiopathy with acute interstitial nephritis. This is the first case report on acyclovir causing thrombotic microaniopathy with partial improvement in renal function after plasmapharesis. PMID:28356666

  18. Drug-Induced Sleep Endoscopy.

    PubMed

    Charakorn, Natamon; Kezirian, Eric J

    2016-12-01

    Drug-induced sleep endoscopy (DISE) is an upper airway evaluation technique in which fiberoptic examination is performed under conditions of unconscious sedation. Unique information obtained from this 3-dimensional examination of the airway potentially provides additive benefits to other evaluation methods to guide treatment selection. This article presents recommendations regarding DISE technique and the VOTE Classification system for reporting DISE findings and reviews the evidence concerning DISE test characteristics and the association between DISE findings and treatment outcomes.

  19. Local Anesthetic-Induced Neurotoxicity

    PubMed Central

    Verlinde, Mark; Hollmann, Markus W.; Stevens, Markus F.; Hermanns, Henning; Werdehausen, Robert; Lirk, Philipp

    2016-01-01

    This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk factors for perioperative nerve injury include regional block technique, patient risk factors, and local anesthetic-induced neurotoxicity. Surgery can lead to nerve damage by use of tourniquets or by direct mechanical stress on nerves, such as traction, transection, compression, contusion, ischemia, and stretching. Current literature suggests that the majority of perioperative nerve injuries are unrelated to regional anesthesia. Besides the blockade of sodium channels which is responsible for the anesthetic effect, systemic local anesthetics can have a positive influence on the inflammatory response and the hemostatic system in the perioperative period. However, next to these beneficial effects, local anesthetics exhibit time and dose-dependent toxicity to a variety of tissues, including nerves. There is equivocal experimental evidence that the toxicity varies among local anesthetics. Even though the precise order of events during local anesthetic-induced neurotoxicity is not clear, possible cellular mechanisms have been identified. These include the intrinsic caspase-pathway, PI3K-pathway, and MAPK-pathways. Further research will need to determine whether these pathways are non-specifically activated by local anesthetics, or whether there is a single common precipitating factor. PMID:26959012

  20. Chemotherapy-induced peripheral neuropathy.

    PubMed

    Fehrenbacher, Jill C

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is common in patients receiving anticancer treatment and can affect survivability and long-term quality of life of the patient following treatment. The symptoms of CIPN primarily include abnormal sensory discrimination of touch, vibration, thermal information, and pain. There is currently a paucity of pharmacological agents to prevent or treat CIPN. The lack of efficacious therapeutics is due, at least in part, to an incomplete understanding of the mechanisms by which chemotherapies alter the sensitivity of sensory neurons. Although the clinical presentation of CIPN can be similar with the various classes of chemotherapeutic agents, there are subtle differences, suggesting that each class of drugs might induce neuropathy via different mechanisms. Multiple mechanisms have been proposed to underlie the development and maintenance of neuropathy; however, most pharmacological agents generated from preclinical experiments have failed to alleviate the symptoms of CIPN in the clinic. Further research is necessary to identify the specific mechanisms by which each class of chemotherapeutics induces neuropathy.

  1. Induced radioactivity in LDEF components

    NASA Technical Reports Server (NTRS)

    Harmon, B. A.; Fishman, G. J.; Parnell, T. A.; Laird, C. E.

    1991-01-01

    The systematics of induced radioactivity on the Long Duration Exposure Facility (LDEF) were studied in a wide range of materials using low level background facilities for detection of gamma rays. Approx. 400 samples of materials processed from structural parts of the spacecraft, as well as materials from onboard experiments, were analyzed at national facilities. These measurements show the variety of radioisotopes that are produced with half-lives greater than 2 wks, most of which are characteristic of proton induced reactions above 20 MeV. For the higher activity, long lived isotopes, it was possible to map the depth and directional dependences of the activity. Due to the stabilized configuration of the LDEF, the induced radioactivity data clearly show contributions from the anisotropic trapped proton flux in the South Atlantic Anomaly. This effect is discussed, along with evidence for activation by galactic protons and thermal neutrons. The discovery of Be-7 was made on leading side parts of the spacecraft, although this was though not to be related to the in situ production of radioisotopes from external particle fluxes.

  2. [Drug-induced oral ulcerations].

    PubMed

    Madinier, I; Berry, N; Chichmanian, R M

    2000-06-01

    Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

  3. Efficient treatment of induced dipoles

    PubMed Central

    Simmonett, Andrew C.; Pickard, Frank C.; Shao, Yihan; Cheatham, Thomas E.; Brooks, Bernard R.

    2015-01-01

    Most existing treatments of induced dipoles in polarizable molecular mechanics force field calculations use either the self-consistent variational method, which is solved iteratively, or the “direct” approximation that is non-iterative as a result of neglecting coupling between induced dipoles. The variational method is usually implemented using assumptions that are only strictly valid under tight convergence of the induced dipoles, which can be computationally demanding to enforce. In this work, we discuss the nature of the errors that result from insufficient convergence and suggest a strategy that avoids such problems. Using perturbation theory to reintroduce the mutual coupling into the direct algorithm, we present a computationally efficient method that combines the precision of the direct approach with the accuracy of the variational approach. By analyzing the convergence of this perturbation series, we derive a simple extrapolation formula that delivers a very accurate approximation to the infinite order solution at the cost of only a few iterations. We refer to the new method as extrapolated perturbation theory. Finally, we draw connections to our previously published permanent multipole algorithm to develop an efficient implementation of the electric field and Thole terms and also derive some necessary, but not sufficient, criteria that force field parameters must obey. PMID:26298123

  4. Chromium-induced kidney disease

    SciTech Connect

    Wedeen, R.P. ); Qian, Lifen )

    1991-05-01

    Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of {beta}{sub 2}-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome palters and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chromic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced chromic renal disease cannot be interpreted as evidence of the absence of such injury.

  5. Field induced gap infrared detector

    NASA Technical Reports Server (NTRS)

    Elliott, C. Thomas (Inventor)

    1990-01-01

    A tunable infrared detector which employs a vanishing band gap semimetal material provided with an induced band gap by a magnetic field to allow intrinsic semiconductor type infrared detection capabilities is disclosed. The semimetal material may thus operate as a semiconductor type detector with a wavelength sensitivity corresponding to the induced band gap in a preferred embodiment of a diode structure. Preferred semimetal materials include Hg(1-x)Cd(x)Te, x is less than 0.15, HgCdSe, BiSb, alpha-Sn, HgMgTe, HgMnTe, HgZnTe, HgMnSe, HgMgSe, and HgZnSe. The magnetic field induces a band gap in the semimetal material proportional to the strength of the magnetic field allowing tunable detection cutoff wavelengths. For an applied magnetic field from 5 to 10 tesla, the wavelength detection cutoff will be in the range of 20 to 50 micrometers for Hg(1-x)Cd(x)Te alloys with x about 0.15. A similar approach may also be employed to generate infrared energy in a desired band gap and then operating the structure in a light emitting diode or semiconductor laser type of configuration.

  6. Statistical Seismology and Induced Seismicity

    NASA Astrophysics Data System (ADS)

    Tiampo, K. F.; González, P. J.; Kazemian, J.

    2014-12-01

    While seismicity triggered or induced by natural resources production such as mining or water impoundment in large dams has long been recognized, the recent increase in the unconventional production of oil and gas has been linked to rapid rise in seismicity in many places, including central North America (Ellsworth et al., 2012; Ellsworth, 2013). Worldwide, induced events of M~5 have occurred and, although rare, have resulted in both damage and public concern (Horton, 2012; Keranen et al., 2013). In addition, over the past twenty years, the increase in both number and coverage of seismic stations has resulted in an unprecedented ability to precisely record the magnitude and location of large numbers of small magnitude events. The increase in the number and type of seismic sequences available for detailed study has revealed differences in their statistics that previously difficult to quantify. For example, seismic swarms that produce significant numbers of foreshocks as well as aftershocks have been observed in different tectonic settings, including California, Iceland, and the East Pacific Rise (McGuire et al., 2005; Shearer, 2012; Kazemian et al., 2014). Similarly, smaller events have been observed prior to larger induced events in several occurrences from energy production. The field of statistical seismology has long focused on the question of triggering and the mechanisms responsible (Stein et al., 1992; Hill et al., 1993; Steacy et al., 2005; Parsons, 2005; Main et al., 2006). For example, in most cases the associated stress perturbations are much smaller than the earthquake stress drop, suggesting an inherent sensitivity to relatively small stress changes (Nalbant et al., 2005). Induced seismicity provides the opportunity to investigate triggering and, in particular, the differences between long- and short-range triggering. Here we investigate the statistics of induced seismicity sequences from around the world, including central North America and Spain, and

  7. Ion beam induced luminescence: Relevance to radiation induced bystander effects

    NASA Astrophysics Data System (ADS)

    Ahmad, S. B.; McNeill, F. E.; Byun, S. H.; Prestwich, W. V.; Seymour, C.; Mothersill, C. E.

    2012-10-01

    The aim of this work is quantify the light emitted as a result of charged particle interaction in materials which may be of relevance to radiation induced "bystander effects" studies. We have developed a system which employs single photon counting to measure the light emitted from samples irradiated under vacuum by a charged particle beam. The system uses a fast photomultiplier tube with a peak cathode response at 420 nm. It has been tested in a proof-of-principle experiment using polystyrene targets. Light output, as a result of irradiation, was measured. The luminescence yield appears to have a non-linear behavior with the incident ion fluence: it rises exponentially to an asymptotic value. The target was irradiated with beam energies varying from 1 to 2 MeV and showed saturation at or before an incident fluence rate of 3 × 1013 H+/cm2 s. The average saturation value for the photon output was found to be 40 × 106 cps. Some measurements were performed using filters to study the emission at specific wavelengths. In the case of filtered light measurements, the photon output was found to saturate at 28 × 103, 10 × 106, and 35 × 106 cps for wavelengths of 280 ± 5 nm, 320 ± 5 nm and 340 ± 5 nm respectively. The light output reaches a maximum value because of damage induced in the polymer. Our measurements indicate a "damage cross section" of the order of 10-14 cm2. The average radiant intensity was found to increase at wavelengths of 280 and 320 nm when the proton energy was increased. This was not found to occur at 340 nm. In conclusion, the light emission at specific wavelengths was found to depend upon the incident proton fluence and the proton energy. The wavelengths of the emitted light measured in this study have significance for the understanding of radiation induced bystander effects.

  8. Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in rats.

    PubMed

    Liu, Hong; Ding, Da-lian; Jiang, Hai-yan; Wu, Xue-wen; Salvi, Richard; Sun, Hong

    2011-10-01

    It is well known that ethacrynic acid (EA) can potentiate the ototoxicity of aminoglycoside antibiotics (AmAn) such as kanamycin (KM), if they were applied at the same time. Currently, to create the model of EA-KM-induced cochlear lesion in rats, adult rats received a single injection of EA (75 mg/kg, intravenous injection), or followed immediately by KM (500 mg/kg, intramuscular injection). The hearing function was assessed by auditory brainstem response (ABR) measurement in response to click and/or tone bursts at 4, 8, 12, 16, 20, 24, and 32 kHz. The static microcirculation status in the stria vascularis after a single EA injection was evaluated with eosin staining. The pathological changes in cochlear and vestibular hair cells were also quantified after co-administration of EA and KM. After a single EA injection, blood flow in vessels supplying the stria vascularis rapidly diminished. However, the blood supply to the cochlear lateral wall partially recovered 5 h after EA treatment. Threshold changes in ABR were basically parallel to the microcirculation changes in stria vascularis after single EA treatment. Importantly, disposable co-administration of EA and KM resulted in a permanent hearing loss and severe damage to the cochlear hair cells, but spared the vestibular hair cells. Since the cochlear lateral wall is the important part of the blood-cochlea barrier, EA-induced anoxic damage to the epithelium of stria vascularis may enhance the entry of KM to the cochlea. Thus, experimental animal model of selective cochlear damage with normal vestibular systems can be reliably created through co-administration of EA and KM.

  9. Homocysteine induces inflammatory transcriptional signaling in monocytes.

    PubMed

    Meng, Shu; Ciment, Stephen; Jan, Michael; Tran, Tran; Pham, Hung; Cueto, Ramon; Yang, Xiao-Feng; Wang, Hong

    2013-01-01

    Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. Here, we studied transcriptional regulation in homocysteine (Hcy)-induced gene expression in monocytes (MC). We identified 11 Hcy-induced genes, 17 anti-inflammatory cytokine interleukin 10-induced, 8 pro-inflammatory cytokine interferon gamma (IFN gamma)-induced and 8 pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha)-induced genes through literature search. Binding frequency of 36 transcription factors (TFs) implicated in inflammation and MC differentiation were analyzed within core promoter regions of identified genes, and classified into 3 classes based on the significant binding frequency to the promoter of Hcy-induced genes. Class 1 TFs exert high significant binding frequency in Hcy-induced genes. Class 2 and 3 TFs have low and no significant binding frequency, respectively. Class 1 TF binding occurrence in Hcy-induced genes is similar to that in IFN gamma -induced genes, but not that in TNF alpha -induced. We conclude that Hcy is a pro-inflammatory amino acid and induces inflammatory transcriptional signal pathways mediated by class 1 TF. We term class 1 TF as putative Hcy-responsive TFs.

  10. Homocysteine induces inflammatory transcriptional signaling in monocytes

    PubMed Central

    Meng, Shu; Ciment, Stephen; Jan, Michael; Tran, Tran; Pham, Hung; Cueto, Ramón; Yang, Xiao-Feng; Wang, Hong

    2013-01-01

    Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. This study is to investigate transcriptional mechanism underlying homocysteine (Hcy)-induced and monocytes (MC)-derived inflammatory response. We identified 11 Hcy-induced genes, 17 anti-inflammatory cytokine interleukin 10-induced, 8 pro-inflammatory cytokine interferon γ (IFNγ)-induced and 8 pro-inflammatory cytokine tumor necrosis factor α (TNFα)-induced genes through literature search. Binding frequency of 36 transcription factors (TFs) implicated in inflammation and MC differentiation were analyzed within core promoter regions of identified genes, and classified into 3 classes based on the significant binding frequency to the promoter of Hcy-induced genes. Class 1 TFs exert high significant binding frequency in Hcy-induced genes. Class 2 and 3 TFs have low and no significant binding frequency, respectively. Class 1 TF binding occurrence in Hcy-induced genes is similar to that in IFNγ-induced genes, but not that in TNFα-induced. We conclude that Hcy is a pro-inflammatory amino acid and induces inflammatory transcriptional signal pathways mediated by class 1 TF. We term class 1 TF, which includes heat shock factor, MC enhancer factor-2, nuclear factor of activated T-cells, nuclear factor kappa light chain enhancer of activated B cells and Krueppel-like factor 4, as putative Hcy-responsive TFs. PMID:23276953

  11. High homocysteine induces betaine depletion

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J.

    2015-01-01

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI—LC–MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. PMID:26182429

  12. High homocysteine induces betaine depletion.

    PubMed

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J

    2015-04-28

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte.

  13. Vibrational excitation induces double reaction.

    PubMed

    Huang, Kai; Leung, Lydie; Lim, Tingbin; Ning, Zhanyu; Polanyi, John C

    2014-12-23

    Electron-induced reaction at metal surfaces is currently the subject of extensive study. Here, we broaden the range of experimentation to a comparison of vibrational excitation with electronic excitation, for reaction of the same molecule at the same clean metal surface. In a previous study of electron-induced reaction by scanning tunneling microscopy (STM), we examined the dynamics of the concurrent breaking of the two C-I bonds of ortho-diiodobenzene physisorbed on Cu(110). The energy of the incident electron was near the electronic excitation threshold of E0=1.0 eV required to induce this single-electron process. STM has been employed in the present work to study the reaction dynamics at the substantially lower incident electron energies of 0.3 eV, well below the electronic excitation threshold. The observed increase in reaction rate with current was found to be fourth-order, indicative of multistep reagent vibrational excitation, in contrast to the first-order rate dependence found earlier for electronic excitation. The change in mode of excitation was accompanied by altered reaction dynamics, evidenced by a different pattern of binding of the chemisorbed products to the copper surface. We have modeled these altered reaction dynamics by exciting normal modes of vibration that distort the C-I bonds of the physisorbed reagent. Using the same ab initio ground potential-energy surface as in the prior work on electronic excitation, but with only vibrational excitation of the physisorbed reagent in the asymmetric stretch mode of C-I bonds, we obtained the observed alteration in reaction dynamics.

  14. Sad music induces pleasant emotion.

    PubMed

    Kawakami, Ai; Furukawa, Kiyoshi; Katahira, Kentaro; Okanoya, Kazuo

    2013-01-01

    In general, sad music is thought to cause us to experience sadness, which is considered an unpleasant emotion. As a result, the question arises as to why we listen to sad music if it evokes sadness. One possible answer to this question is that we may actually feel positive emotions when we listen to sad music. This suggestion may appear to be counterintuitive; however, in this study, by dividing musical emotion into perceived emotion and felt emotion, we investigated this potential emotional response to music. We hypothesized that felt and perceived emotion may not actually coincide in this respect: sad music would be perceived as sad, but the experience of listening to sad music would evoke positive emotions. A total of 44 participants listened to musical excerpts and provided data on perceived and felt emotions by rating 62 descriptive words or phrases related to emotions on a scale that ranged from 0 (not at all) to 4 (very much). The results revealed that the sad music was perceived to be more tragic, whereas the actual experiences of the participants listening to the sad music induced them to feel more romantic, more blithe, and less tragic emotions than they actually perceived with respect to the same music. Thus, the participants experienced ambivalent emotions when they listened to the sad music. After considering the possible reasons that listeners were induced to experience emotional ambivalence by the sad music, we concluded that the formulation of a new model would be essential for examining the emotions induced by music and that this new model must entertain the possibility that what we experience when listening to music is vicarious emotion.

  15. Metabolic Stress Induced by Arginine Deprivation Induces Autophagy Cell Death in Prostate Cancer

    DTIC Science & Technology

    2010-08-01

    Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis. Cancer Research, 69(2):700-708...TITLE: Metabolic stress induced by arginine deprivation induces autophagy cell death in prostate cancer PRINCIPAL INVESTIGATOR: Richard Bold, MD...4. TITLE AND SUBTITLE Metabolic stress induced by arginine deprivation induces autophagy cell 5a. CONTRACT NUMBER death in prostate cancer 5b

  16. Spallation-induced fission reactions

    NASA Astrophysics Data System (ADS)

    Benlliure, J.; Rodríguez-Sánchez, J. L.

    2017-03-01

    During the last decade spallation-induced fission reactions have received particular attention because of their impact in the design of spallation-neutron sources or radioactive beam facilities, but also in the understanding of the fission process at high excitation energy. In this paper, we review the main progress brought by modern experimental techniques, in particular those based in the inverse kinematic, as well as the achievements in modelling these reactions. We will also address future possibilities for improving the investigation of fission dynamics.

  17. Sertraline-induced ventricular tachycardia.

    PubMed

    Patel, Nishit H; Golwala, Harsh; Stavrakis, Stavros; Schechter, Eliot

    2013-01-01

    Sertraline is a selective serotonin reuptake inhibitor, which is a commonly used drug for major depressive disorder. Most frequently reported adverse effects of sertraline in patients receiving 50-150 mg/d are dry mouth, headache, diarrhea, nausea, vomiting, sweating, and dizziness. We hereby report one of the few cases of sertraline-induced ventricular tachycardia, which has been for the first time objectively assessed by the Naranjo scale. We therefore urge the primary care physicians and the cardiologists to keep sertraline as a possible precipitating factor for evaluation of ventricular tachycardia.

  18. Auditory hallucinations induced by trazodone.

    PubMed

    Shiotsuki, Ippei; Terao, Takeshi; Ishii, Nobuyoshi; Hatano, Koji

    2014-04-03

    A 26-year-old female outpatient presenting with a depressive state suffered from auditory hallucinations at night. Her auditory hallucinations did not respond to blonanserin or paliperidone, but partially responded to risperidone. In view of the possibility that her auditory hallucinations began after starting trazodone, trazodone was discontinued, leading to a complete resolution of her auditory hallucinations. Furthermore, even after risperidone was decreased and discontinued, her auditory hallucinations did not recur. These findings suggest that trazodone may induce auditory hallucinations in some susceptible patients.

  19. Auditory hallucinations induced by trazodone

    PubMed Central

    Shiotsuki, Ippei; Terao, Takeshi; Ishii, Nobuyoshi; Hatano, Koji

    2014-01-01

    A 26-year-old female outpatient presenting with a depressive state suffered from auditory hallucinations at night. Her auditory hallucinations did not respond to blonanserin or paliperidone, but partially responded to risperidone. In view of the possibility that her auditory hallucinations began after starting trazodone, trazodone was discontinued, leading to a complete resolution of her auditory hallucinations. Furthermore, even after risperidone was decreased and discontinued, her auditory hallucinations did not recur. These findings suggest that trazodone may induce auditory hallucinations in some susceptible patients. PMID:24700048

  20. Cocaine-induced mesenteric ischaemia.

    PubMed

    Osorio, J; Farreras, N; Ortiz De Zárate L; Bachs, E

    2000-01-01

    We report a 33-year-old man with distal ileum infarction after intravenous abuse of cocaine. He underwent resection of a gangrenous bowel segment and survived. We review the literature regarding intestinal ischaemia related to cocaine. To date, 19 cases have been published. Like most previously reported cases, our patient was young and had no previous history of arteriosclerosis. He suffered cocaine-induced rhabdomyolysis and acute renal failure. Mesenteric ischaemia should be considered in the differential diagnosis of acute or chronic abdominal pain in cocaine consumers.

  1. Fluoroquinolone-induced Achilles tendinitis.

    PubMed

    Tam, P K; Ho, Carmen T K

    2014-12-01

    We report a case of Achilles tendinitis after intake of ciprofloxacin for treatment of respiratory tract infection. Fluoroquinolone-induced tendinopathy is an uncommon but increasingly recognised adverse effect of this antibiotic class. Most of the cases occur in the Achilles tendon and may lead to tendon rupture. Possible predisposing risk factors include use of steroid, patients with renal impairment or renal transplant, old age, and being an athlete. The drug should be stopped once this condition is suspected. Symptomatic treatment should be given and orthopaedic referral is desirable if tendon rupture occurs.

  2. [Pregnancy-induced haemolytic anaemia].

    PubMed

    Karagiozova, J; Masseva, A; Ivanov, St; Marinov, B; Kulinska, R; Boiadjiev, D; Jordanova, D

    2014-01-01

    This is the clinical case of a primiparous eight month pregnant female, presenting with symptoms of pregnancy-induced acute haemolytic anaemia (haemolytic aneamia provoked by an immune mechanism, intra- and extra-erythrocyte defects, and HELLP syndrome were excluded). The anaemia progressed to become life-threatening for both the pregnant women and the foetus, which brought the following questions into consideration: diagnosis of anaemia during pregnancy; dosing of corticosteroid therapy; possibility of giving birth to a viable foetus and prognosis for next pregnancies. Owing to the inter-disciplinary efforts, the life and health of this pregnant woman were preserved, but the foetus was lost.

  3. Metronidazole-Induced Cerebellar Toxicity

    PubMed Central

    Agarwal, Amit; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

    2016-01-01

    Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy. PMID:27127600

  4. Airway management: induced tension pneumoperitoneum

    PubMed Central

    Ahmed, Khedher; Amine, El Ghali Mohamed; Abdelbaki, Azouzi; Jihene, Ayachi; Khaoula, Meddeb; Yamina, Hamdaoui; Mohamed, Boussarsar

    2016-01-01

    Pneumoperitoneum is not always associated with hollow viscus perforation. Such condition is called non-surgical or spontaneous pneumoperitoneum. Intrathoracic causes remain the most frequently reported mechanism inducing this potentially life threatening complication. This clinical condition is associated with therapeutic dilemma. We report a case of a massive isolated pneumoperitoneum causing acute abdominal hypertension syndrome, in a 75 year female, which occurred after difficult airway management and mechanical ventilation. Emergent laparotomy yielded to full recovery. The recognition of such cases for whom surgical management can be avoided is primordial to avoid unnecessary laparotomy and its associated morbidity particularly in the critically ill.

  5. HYPOGLYCEMIA INDUCED BY ANTIDIABETIC SULFONYLUREAS.

    PubMed

    Confederat, Luminiţa; Constantin, Sandra; Lupaşcu, Florentina; Pânzariu, Andreea; Hăncianu, Monica; Profire, Lenuţa

    2015-01-01

    Diabetes mellitus is a major health problem due to its increasing prevalence and life-threatening complications. Antidiabetic sulfonylureas represent the first-line drugs in type 2 diabetes even though the most common associated risk is pharmacologically-induced hypoglycemia. In the development of this side effect are involved several factors including the pharmacokinetic and pharmacodynamic profile of the drug, patient age and behavior, hepatic or renal dysfunctions, or other drugs associated with a high risk of interactions. If all these are controlled, the risk-benefit balance can be equal to other oral antidiabetic drugs.

  6. Ion-induced nuclear radiotherapy

    DOEpatents

    Horn, Kevin M.; Doyle, Barney L.

    1996-01-01

    Ion-induced Nuclear Radiotherapy (INRT) is a technique for conducting radiosurgery and radiotherapy with a very high degree of control over the spatial extent of the irradiated volume and the delivered dose. Based upon the concept that low energy, ion induced atomic and nuclear reactions can be used to produce highly energetic reaction products at the site of a tumor, the INRT technique is implemented through the use of a conduit-needle or tube which conducts a low energy ion beam to a position above or within the intended treatment area. At the end of the conduit-needle or tube is a specially fabricated target which, only when struck by the ion beam, acts as a source of energetic radiation products. The inherent limitations in the energy, and therefore range, of the resulting reaction products limits the spatial extent of irradiation to a pre-defined volume about the point of reaction. Furthermore, since no damage is done to tissue outside this irradiated volume, the delivered dose may be made arbitrarily large. INRT may be used both as a point-source of radiation at the site of a small tumor, or as a topical bath of radiation to broad areas of diseased tissue.

  7. Chemotherapy-induced hair loss.

    PubMed

    Trüeb, R M

    2010-01-01

    Chemotherapy-induced hair loss occurs with an estimated incidence of 65%. Forty-seven percent of female patients consider hair loss to be the most traumatic aspect of chemotherapy and 8% would decline chemotherapy due to fears of hair loss. At present, no approved pharmacologic intervention exists to circumvent this side-effect of anticancer treatment, though a number of agents have been investigated on the basis of the current understanding of the underlying pathobiology. Among the agents that have been evaluated, topical minoxidil was able to reduce the severity or shorten the duration, but it did not prevent hair loss. The major approach to minimize chemotherapy-induced hair loss is by scalp cooling, though most published data on this technique are of poor quality. Fortunately, the condition is usually reversible, and appropriate hair and scalp care along with temporarily wearing a wig may represent the most effective coping strategy. However, some patients may show changes in color and/or texture of regrown hair, and in limited cases the reduction in density may persist.

  8. [Autoimmune hepatitis induced by isotretionine].

    PubMed

    Guzman Rojas, Patricia; Gallegos Lopez, Roxana; Ciliotta Chehade, Alessandra; Scavino, Yolanda; Morales, Alejandro; Tagle, Martín

    2016-01-01

    We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto’s hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (®Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirrubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis.

  9. Preference pulses induced by reinforcement.

    PubMed

    Hachiga, Yosuke; Sakagami, Takayuki; Silberberg, Alan

    2014-11-01

    Eight rats responded on concurrent Variable-Ratio 20 Extinction schedules for food reinforcement. The assignment of variable-ratio reinforcement to a left or right lever varied randomly following each reinforcer, and was cued by illumination of a stimulus light above that lever. Postreinforcement preference levels decreased substantially and reliably over time when the lever that just delivered reinforcement was now in extinction; however, if that lever was once again associated with variable ratio, this decrease in same-lever preference tended to be small, and for some subjects, not in evidence. The changes in preference level to the extinction lever were well described by a modified version of Killeen, Hanson, and Osborne's (1978) induction model. Consistent with this model's attribution of preference change to induction, we attribute preference change in this report to a brief period of reinforcer-induced arousal that energizes responding to the lever that delivered the last reinforcer. After a few seconds, this induced responding diminishes, and the operant responding that remains comes under the control of the stimulus light cuing the lever providing variable-ratio reinforcement.

  10. Radiation-induced cardiovascular effects

    NASA Astrophysics Data System (ADS)

    Tapio, Soile

    Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in