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Sample records for rat periventricular nucleus

  1. Somatostatin in the rat periventricular nucleus: sex differences and effect of gonadal steroids

    PubMed Central

    Van Vugt, Harmke H.; Van de Heijning, Bert J. M.

    2008-01-01

    In the rat, the sexual dimorphism in growth hormone release is driven by sex steroids, and is suggested to result mainly from differences in somatostatin (SOM) release patterns from the median eminence. We studied the effect of gonadal steroids on SOM peptide-containing cells in the periventricular nucleus (PeVN) of ovariectomized (OVX) female rats, and compared these data with data from intact male rats. Adult female rats were treated with estradiol (E2) and/or progesterone (P), 3 months (long-term) or 2 weeks (short-term) after ovariectomy (OVX). Perfusion-fixed brains were sliced and stained, and the number of SOM-immunoreactive (-ir) cells and total SOM-ir area (in μm2) were determined using computer assisted analysis. SOM-ir cells in the PeVN showed a very characteristic rostro-caudal distribution and localization in relation to the third ventricle. Both the number of SOM-ir cells and total SOM-ir area in the PeVN were higher in male compared to OVX female rats. Neither the number of SOM-ir cells, nor the total SOM-ir area in the PeVN was affected by E2 or P treatment alone. Treatment with both gonadal steroids, however, did increase total SOM-immunoreactivity. This study is the first to describe SOM cell distribution within the rat PeVN in great detail. A clear sex difference exists in SOM peptide content in the rat PeVN. In addition, E2 and P may act synergistically to affect SOM cells in the female PeVN, suggesting that both gonadal steroids may be involved in the generation of the typical feminine SOM release pattern. PMID:18421448

  2. [Effect of exogenous androgen on structures of sexually dimorphism nucleus in preoptic area and anteroventral periventricular nucleus before sexual differentiation in female rats].

    PubMed

    Huang, Man-li; Wei, Ning; Hu, Jian-bo; Xu, Yi

    2008-09-01

    To investigate the effects of androgen on sexually dimorphism nucleus in preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV) before sexual differentiation of the brain in female rats. Neonatal female SD rats (n=12) were randomly divided into two groups: androgen group and control group. Twenty-four hours after birth animals were subjected to intraperitoneal injection of 50 microl of testosterone propionate (TP,10.0 g/L) or aseptic oil as control. The rats were sacrificed 60 days after the injection and the brains were collected for crystal violet staining. LEICA Q Win system was applied in detecting the boundaries of SDN-POA and AVPV, then the volumes of SDN-POA and AVPV were calculated. The volumes of SDN-POA in androgen group were significantly larger than those in control group [(16.77+/-2.68) vs (8.99+/-1.42)mm(3)x10(-3), P<0.01], while the volumes of AVPV in androgen group were significantly smaller than those in control group [(9.14+/-1.16) vs (14.62+/-2.80)mm(3)x10(-3), P<0.01]. Exogenous androgen rendered before sexual differentiation in female rats results in enlargement of SDN-POA volumes and reduction of AVPV.

  3. Neonatal stimulation of 5-HT(2) receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area.

    PubMed

    Dakin, C L; Wilson, C A; Kalló, I; Coen, C W; Davies, D C

    2008-05-01

    Masculinization of the brain is dependent upon a perinatal surge in testosterone. It also requires a transient decrease in hypothalamic 5-HT concentration and turnover and an increase in androgen receptor (AR) expression during the second postnatal week. We have previously shown that increasing 5-HT activity over this period in male or androgenized female rats feminizes their adult behaviour and also feminizes the size of their anteroventral periventricular nucleus (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN-POA). To investigate the role of 5-HT in sexual differentiation of the brain, 5-HT activity was raised over postnatal days 8-16 in male, female and androgenized female rats by daily administration of the 5-HT(2) receptor agonist (-)[2,5 dimethoxy-4-iodophenyl]-2-amino propane hydrochloride [(-)DOI]. By postnatal day 18, the size of the AVPV and SDN-POA was sexually dimorphic; their sizes were feminized by (-)DOI treatment. In the absence of (-)DOI treatment, there were significantly more AR-immunoreactive cells in the AVPV of males, and in the SDN-POA of males and androgenized females, than in those of females on postnatal day 18. (-)DOI treatment reduced the number of AR-immunoreactive cells in the AVPV and SDN-POA of males and androgenized females, but not of females, by postnatal day 18. These results suggest that 5-HT(2) receptor activation can influence sexual differentiation of the brain by controlling AR expression.

  4. Sexually dimorphic expression of estrogen receptor β in the anteroventral periventricular nucleus of the rat preoptic area: Implication in luteinizing hormone surge

    PubMed Central

    Orikasa, Chitose; Kondo, Yasuhiko; Hayashi, Shinji; McEwen, Bruce S.; Sakuma, Yasuo

    2002-01-01

    Striking sex difference was detected in the expression of estrogen receptor (ER) β mRNA and protein by nonisotopic in situ hybridization and immunohistochemistry in the anteroventral periventricular nucleus (AVPV) of the rat preoptic area. In females more than in males, a significantly larger number of ERβ mRNA-positive cells were visualized in the medial-most portion of the AVPV within 50 μm from the ependymal lining of the third ventricle. Rats of 7, 14, 21, 35, and 60 days of age (d 1 = day of birth) showed the sex difference. Orchidectomy of male neonates or estrogen treatment of female pups reversed the brain phenotype when examined on d 14. In the AVPV of adult females, ERα immunoreactivity colocalized in 83% of ERβ mRNA-positive cells. Tyrosine hydroxylase immunoreactivity colocalized in 18% of ERβ immunoreactive cells in d 21 females. Infusion of an ERβ antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERβ-immunoreactive cells in the AVPV. These findings provide support for the hypothesis that activation of ERβ in the AVPV is an important regulatory event in the female-typical induction of luteinizing hormone surge by estrogen. PMID:11854469

  5. 17β-estradiol and progesterone regulate multiple progestin signaling molecules in the anteroventral periventricular nucleus, ventromedial nucleus and sexually dimorphic nucleus of the preoptic area in female rats.

    PubMed

    Intlekofer, K A; Petersen, S L

    2011-03-10

    Recent work identified novel progestin signaling molecules, including progesterone receptor membrane component 1 (Pgrmc1), Pgrmc2, serpine mRNA binding protein 1 (Serbp1), progestin and adiponectin receptors 7 (Paqr7) and Paqr8. These molecules mediate rapid progesterone (P(4)) effects in non-neural tissue and we recently mapped their expression in the brain. Many rapid effects of P(4) require 17β-estradiol (E(2)) and P(4) priming; therefore, we examined the effects of ovarian hormones on the expression of these non-classical progestin signaling molecules. We focused specifically on the anteroventral periventricular nucleus (AVPV), the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the ventrolateral portion of the ventromedial nucleus (VMNvl). These brain nuclei are important for female reproduction. Ovariectomized adult female rats were implanted with capsules containing sesame oil or E(2), and injected 48 h later with sesame oil or P(4). Brains were collected 8 h later and RNA was isolated from the AVPV, SDN-POA and VMNvl. We assessed the effects of ovarian hormones on mRNA levels using quantitative polymerase chain reaction (QPCR). In the AVPV, Serbp1 mRNA levels were increased by P(4) in the presence of E(2), and Paqr8 was downregulated by P(4) alone. In the SDN-POA, combined E(2) and P(4) increased Pgrmc1 and Serbp1 mRNA levels, and E(2) alone increased Paqr8 mRNA levels. Finally, in the VMNvl, P(4) increased mRNA levels encoding Pgrmc1, Pgrmc2 and Serbp1, and the combination of E(2) and P(4) increased Pgrmc1 and Serbp1 mRNA levels. Paqr7 was not regulated by E(2) or P(4) in any brain region examined. In summary, we showed that ovarian hormones regulate novel progestin signaling molecules in brain regions important for the neuroendocrine control of reproduction. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Oestrogen-independent circadian clock gene expression in the anteroventral periventricular nucleus in female rats: Possible role as an integrator for circadian and ovarian signals timing the LH surge

    PubMed Central

    Smarr, Benjamin L.; Gile, Jennifer J.; de la Iglesia, Horacio O.

    2013-01-01

    Periodic ovulation in rats, mice and hamsters is the result of a surge in LH that depends on circadian gating signals emerging from the master circadian clock within the suprachiasmatic nucleus (SCN) and rising ovarian oestrogen levels. These two signals converge into the anteroventral periventricular nucleus (AVPV) and lead to the release of kisspeptin, which is responsible for surges of GnRH and, in turn, of LH release. How the AVPV integrates circadian and reproductive signals remains unclear. Here we show that the female rat AVPV itself shows circadian oscillations in the expression of the clock genes PER1 and BMAL1, which lie at the core circadian clockwork of mammals. In ovariectomized (OVX) females treated with estradiol (E2) these oscillations are in synchrony with the AVPV rhythmic expression of the KISS1 gene and the gene that codes for the arginine-vasopressin (AVP) receptor AVPr1a. Whereas clock gene oscillations are independent of oestrogen levels, circadian expression of Kiss1 and Avpr1a (also referred to as V1a) mRNA are respectively blunted and absent in ovariectomized animals without E2 replacement. Because AVP is believed to be a critical SCN transmitter to gate the LH surge, our data suggest that a there is a circadian oscillator located in the AVPV, and that such a putative oscillator could time, in an oestrogen dependent manner, the sensitivity to circadian signals emerging from the SCN and the release of kisspeptin. PMID:24028332

  7. Release of Norepinephrine in the Preoptic Area Activates Anteroventral Periventricular Nucleus Neurons and Stimulates the Surge of Luteinizing Hormone

    PubMed Central

    Poletini, Maristela O.; Leite, Cristiane M.; Bernuci, Marcelo P.; Kalil, Bruna; Mendonça, Leonardo B.D.; Carolino, Ruither O. G.; Helena, Cleyde V. V.; Bertram, Richard; Franci, Celso R.; Anselmo-Franci, Janete A.

    2013-01-01

    The role of norepinephrine (NE) in regulation of LH is still controversial. We investigated the role played by NE in the positive feedback of estradiol and progesterone. Ovarian-steroid control over NE release in the preoptic area (POA) was determined using microdialysis. Compared with ovariectomized (OVX) rats, estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning but increased release coincident with the afternoon surge of LH. OVX rats treated with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release than OVX+E rats, and amplification of the LH surge. The effect of NE on LH secretion was confirmed using reverse microdialysis. The LH surge and c-Fos expression in anteroventral periventricular nucleus neurons were significantly increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase-immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the A1. The selective lesion of LC terminals, by intracerebroventricular N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons, respectively, and this is associated with the increased release of NE in the POA and the magnitude of the LH surge. NE stimulates LH secretion, at least in part, through activation of anteroventral periventricular neurons. These findings contribute to elucidation of the role played by NE during the positive feedback of ovarian steroids. PMID:23150494

  8. Release of norepinephrine in the preoptic area activates anteroventral periventricular nucleus neurons and stimulates the surge of luteinizing hormone.

    PubMed

    Szawka, Raphael E; Poletini, Maristela O; Leite, Cristiane M; Bernuci, Marcelo P; Kalil, Bruna; Mendonça, Leonardo B D; Carolino, Ruither O G; Helena, Cleyde V V; Bertram, Richard; Franci, Celso R; Anselmo-Franci, Janete A

    2013-01-01

    The role of norepinephrine (NE) in regulation of LH is still controversial. We investigated the role played by NE in the positive feedback of estradiol and progesterone. Ovarian-steroid control over NE release in the preoptic area (POA) was determined using microdialysis. Compared with ovariectomized (OVX) rats, estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning but increased release coincident with the afternoon surge of LH. OVX rats treated with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release than OVX+E rats, and amplification of the LH surge. The effect of NE on LH secretion was confirmed using reverse microdialysis. The LH surge and c-Fos expression in anteroventral periventricular nucleus neurons were significantly increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase-immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the A1. The selective lesion of LC terminals, by intracerebroventricular N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons, respectively, and this is associated with the increased release of NE in the POA and the magnitude of the LH surge. NE stimulates LH secretion, at least in part, through activation of anteroventral periventricular neurons. These findings contribute to elucidation of the role played by NE during the positive feedback of ovarian steroids.

  9. GHRP-6-induced changes in electrical activity of single cells in the arcuate, ventromedial and periventricular nucleus neurones [correction of nuclei] of a hypothalamic slice preparation in vitro.

    PubMed

    Hewson, A K; Viltart, O; McKenzie, D N; Dyball, R E; Dickson, S L

    1999-12-01

    Previously, we demonstrated that systemic injection of the growth hormone secretagogue, growth hormone-releasing peptide (GHRP)-6, selectively activated cells in the hypothalamic arcuate nucleus, as reflected by increased electrical activity and induction of the immediate early gene c-fos. The growth hormone secretagogue receptor distribution is not confined to the arcuate nucleus, suggesting that additional sites of action may exist. In the present study we characterized the electrophysiological responses of cells in the arcuate nucleus, ventromedial nucleus and periventricular nucleus in an in-vitro hypothalamic slice preparation, following bath application of GHRP-6. Additionally, since central somatostatin administration has been shown to attenuate the induction of the c-fos gene by GHRP-6, we sought to determine whether the arcuate cells activated by GHRP-6 are also somatostatin-sensitive. Male Wistar rats (100-150 g body weight (BW)) were anaesthetized (urethane; 1.2 g/kg BW) and the brains removed. Coronal sections (400 microm thickness) were cut through a block of hypothalamus and were transferred to a slice chamber perfused with artificial cerebrospinal fluid. Forty-one arcuate nucleus cells were tested with bath application of 15 microm GHRP-6 for 10 min, 16 of which were tested subsequently (>30 min later) with application of 10 microM somatostatin. Following GHRP-6 administration, 19 cells (46. 3%) showed a significant increase in firing rate during the 15-min period after GHRP-6 application (P<0.001), 17 cells (41.5%) did not respond and the remaining five cells (12.2%) were significantly inhibited. Six of the eight arcuate nucleus cells that were excited by GHRP-6 were significantly inhibited by somatostatin. By contrast, five of the six arcuate nucleus cells that were unresponsive to GHRP-6 were also unresponsive to somatostatin. In the ventromedial nucleus, of 19 cells tested, eight cells (42.1%) were excited by GHRP-6, eight cells (42.1%) were

  10. Electrical and morphological characteristics of anteroventral periventricular nucleus kisspeptin and other neurons in the female mouse.

    PubMed

    Ducret, Eric; Gaidamaka, Galina; Herbison, Allan E

    2010-05-01

    Neurons in the rodent anteroventral periventricular nucleus (AVPV) play a key role in integrating circadian and gonadal steroid hormone information in the control of fertility. In particular, estradiol-sensitive kisspeptin neurons located in the AVPV, and adjacent structures [together termed the rostral periventricular area of the third ventricle (RP3V)], are critical for puberty onset and the preovulatory LH surge. The present study aimed to establish the morphological and electrical firing characteristics of RP3V neurons, including kisspeptin neurons, in the adult female mouse. Cell-attached electrical recordings, followed by juxtacellular dye filling, of 129 RP3V neurons in the acute brain slice preparation revealed these cells to exhibit multipolar (53%), bipolar (43%), or unipolar (4%) dendritic morphologies along with silent (16%), irregular (41%), bursting (25%), or tonic (34%) firing patterns. Postrecording immunocytochemistry identified 17 of 100 filled RP3V cells as being kisspeptin neurons, all of which exhibited complex multipolar dendritic trees and significantly (P < 0.05) higher bursting or high tonic firing rates compared with nonkisspeptin neurons. The firing pattern of RP3V neurons fluctuated across the estrous cycle with a significant (P < 0.05) switch from irregular to tonic firing patterns found on proestrus. A similar nonsignificant trend was found for kisspeptin neurons. All RP3V neurons responded to gamma-aminobutyric acid and glutamate, about 10% to RFamide-related peptide-3, about 5% to vasopressin, 0% to vasoactive intestinal peptide, and 0% to kisspeptin. These studies provide a morphological and electrical description of AVPV/RP3V neurons and demonstrate their cycle-dependent firing patterns along with an unexpected lack of acute response to the circadian neuropeptides.

  11. 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.

  12. 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

  13. Periventricular Leukomalacia

    MedlinePlus

    ... tissue. The periventricular area-the area around the spaces in the brain called ventricles-contains nerve fibers ... tissue. The periventricular area-the area around the spaces in the brain called ventricles-contains nerve fibers ...

  14. Kisspeptin expression features in the arcuate and anteroventral periventricular nuclei of hypothalamus of letrozole-induced polycystic ovarian syndrome in rats.

    PubMed

    Aliabadi, Elham; Namavar, Mohammad Reza; Mortezaee, Keywan; Toolee, Heidar; Keshtgar, Sara; Mirkhani, Hossein; Akbari, Mohammad; Rastegar, Tayebeh; Solhjoo, Somayeh

    2017-09-05

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the reproductive system characterized by polycystic ovaries and androgen excess. Letrozole is a nonsteroidal aromatase inhibitor that is used in experimental research to induce PCOS. Kisspeptin is an essential protein in regulation of cyclicity. Kisspeptin receptor is expressed in the hypothalamus and pituitary glands, and kisspeptin containing neurons are affected from sex steroid hormones. We aimed to investigate the number of kisspeptin-positive cells in the arcuate (Arc) and anteroventral periventricular nuclei (AVPV) of hypothalamus in the letrozole-induced PCOS. 40 female Wistar rats were divided into the proestrus control, diestrus control, proestrus vehicle, diestrus vehicle and letrozole. Animals were sacrificed after 3 weeks, and sera, ovary and brain samples were harvested for further evaluations. Letrozole group had high weight gain, high numbers of ovarian follicular cysts, high levels of luteinizing hormone and testosterone and increase number of kisspeptin-positive cells in the Arc nucleus, as compared with the control groups (P ≤ 0.05 vs. proestrus control and proestrus vehicle). Letrozole group showed a decrease in the number of kisspeptin-positive cells in the AVPV nucleus (P ≤ 0.05 vs. proestrus control and proestrus vehicle). Our findings show that the number of kisspeptin-positive cells may be affected from letrozole, and that the changes in the number of these cells may be in favor of the appearance of PCOS features in this group.

  15. Assessment of Epigenetic Contributions to Sexually-Dimorphic Kiss1 Expression in the Anteroventral Periventricular Nucleus of Mice

    PubMed Central

    Semaan, Sheila J.; Dhamija, Sangeeta; Kim, Joshua; Ku, Eric C.

    2012-01-01

    The Kiss1 gene, which encodes kisspeptin and is critical for reproduction, is sexually differentiated in the hypothalamic anteroventral periventricular (AVPV)/rostral periventricular (PeN) nuclei. Specifically, female rodents have higher AVPV/PeN Kiss1 expression than males, but how this Kiss1 sex difference is induced in early development is poorly understood. Here, we explored the contribution of epigenetic mechanisms to the establishment of the AVPV/PeN Kiss1 sex difference, focusing on histone deacetylation and DNA methylation. First, we utilized postnatal pharmacological blockade of histone deacetylation and analyzed Kiss1 expression in the AVPV/PeN. Postnatal disruption of histone deacetylase modestly increased AVPV Kiss1 cell number in both sexes but did not alter the Kiss1 sex difference. Next, we assessed whether the level of CpG methylation, which can influence transcription factor binding and gene expression, in the murine Kiss1 gene differs between males and females. We found significant sex differences in methylation at several CpG sites in the putative promoter and first intron of the Kiss1 gene in the AVPV/PeN, but not in the arcuate (which lacks adult Kiss1 sex differences), suggesting that differential methylation of the Kiss1 gene may influence sexually-dimorphic Kiss1 expression in the AVPV/PeN. Transgenic impairment of methyl CpG-binding protein-2 function did not eliminate the Kiss1 sex difference, indicating that other methylation factors are involved. Interestingly, CpG methylation in the AVPV/PeN was lower in males than females, suggesting that transcriptional repressors may contribute to the AVPV/PeN Kiss1 sex difference, a possibility supported by in silico identification of putative repressor binding sites near some of the sexually-dimorphic CpG. PMID:22374971

  16. Molecular characterization of circumventricular organs and third ventricle ependyma in the rat: potential markers for periventricular tumors.

    PubMed

    Szathmari, Alexandru; Champier, Jacques; Ghersi-Egea, Jean-François; Jouvet, Anne; Watrin, Chantal; Wierinckx, Anne; Fèvre Montange, Michelle

    2013-02-01

    Circumventricular organs (CVOs) are specialized ventricular structures around the third and fourth ventricles of the brain. In humans, these structures are present during the fetal period and some become vestigial after birth. Some of these organs, such as the pineal gland (PG), subcommissural organ (SCO), and organum vasculosum of the lamina terminalis, might be the sites of origin of periventricular tumors, notably pineal parenchymal tumors, papillary tumor of the pineal region and chordoid glioma. In contrast to the situation in humans, CVOs are present in the adult rat and can be dissected by laser capture microdissection (LCM). In this study, we used LCM and microarrays to analyze the transcriptomes of three CVOs, the SCO, the subfornical organ (SFO), and the PG and the third ventricle ependyma in the adult rat, in order to better characterize these organs at the molecular level. Several genes were expressed only, or mainly, in one of these structures, for example, Erbb2 and Col11a1 in the ependyma, Epcam and Claudin-3 (CLDN3) in the SCO, Ren1 and Slc22a3 in the SFO and Tph, Aanat and Asmt in the PG. The expression of these genes in periventricular tumors should be examined as evidence for a possible origin from the CVOs. Furthermore, we performed an immunohistochemical study of CLDN3, a membrane protein involved in forming cellular tight junctions and found that CLDN3 expression was restricted to the apical pole of ependymocytes in the SCO. This microarray study provides new evidence regarding the possible origin of some rare periventricular tumors.

  17. Periventricular heterotopia.

    PubMed

    Lu, Jie; Sheen, Volney

    2005-09-01

    Periventricular heterotopia (PH) is clinically diagnosed on the basis of the radiographic characteristics of heterotopic nodules composed of disorganized neurons along the lateral ventricles of the brain. Epilepsy is the main presenting symptom of patients with PH. Behaviorally, patients generally are of normal intelligence, although there have been associated findings of learning disabilities, namely, dyslexia. Two genes responsible for PH have been identified: FilaminA, which encodes for the protein filamin A, and ARFGEF2, which encodes for the vesical transport-regulating protein ARFGEF2. The much more common X-linked dominant form of this disorder is due to filamin A, affects females, and is typically lethal in males. A much rarer autosomal recessive form due to ARFGEF2 mutations leads to microcephaly and developmental delay in addition to PH. Cell motility, adhesion defects, and weakening along the neuroepithelial lining may result from defects in these genes during cortical development and contribute to PH, but the mechanisms are not clear yet. Treatment of PH is largely symptomatic, following basic principles for epilepsy management and genetic counseling.

  18. Relative Importance of the Arcuate and Anteroventral Periventricular Kisspeptin Neurons in Control of Puberty and Reproductive Function in Female Rats

    PubMed Central

    Hu, M. H.; Li, X. F.; McCausland, B.; Li, S. Y.; Gresham, R.; Kinsey-Jones, J. S.; Gardiner, J. V.; Sam, A. H.; Bloom, S. R.; Poston, L.; Lightman, S. L.; Murphy, K. G.

    2015-01-01

    Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation, respectively. Using bilateral microinjections of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or AVPV of female rats at postnatal day 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity, and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32% reduction of kisspeptin in the ARC had no effect on the onset of puberty but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signaling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity. PMID:25875299

  19. Relative Importance of the Arcuate and Anteroventral Periventricular Kisspeptin Neurons in Control of Puberty and Reproductive Function in Female Rats.

    PubMed

    Hu, M H; Li, X F; McCausland, B; Li, S Y; Gresham, R; Kinsey-Jones, J S; Gardiner, J V; Sam, A H; Bloom, S R; Poston, L; Lightman, S L; Murphy, K G; O'Byrne, K T

    2015-07-01

    Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation, respectively. Using bilateral microinjections of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or AVPV of female rats at postnatal day 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity, and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32% reduction of kisspeptin in the ARC had no effect on the onset of puberty but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signaling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity.

  20. Electron microscopic analysis of synaptic inputs from the median preoptic nucleus and adjacent regions to the supraoptic nucleus in the rat.

    PubMed

    Armstrong, W E; Tian, M; Wong, H

    1996-09-16

    The median preoptic nucleus (MnPo) is critical for normal fluid balance, mediating osmotically evoked drinking and neurohypophysial hormone secretion. The influence of the MnPo on vasopressin and oxytocin release is in part through direct connections to the supraoptic and paraventricular nucleus. In the present investigation the synaptic contacts between the MnPo and supraoptic neurons were investigated in rats by ultrastructural examination of terminals labeled anterogradely with the tracers Phaseolus vulgaris-leucoagglutinin or biotinylated dextran. At the light microscopic level, labeled fibers within the supraoptic nucleus branched frequently, were punctuated by varicosities, and were distributed throughout the nucleus without preference for the known distributions of oxytocin and vasopressin neurons. At the ultrastructural level, synapses were associated with many of these varicosities. The ratio of labeled axodendritic to axosomatic synapses encountered was roughly consistent with a uniform innervation of dendrites and somata. The great majority of synapses were characterized by symmetrical contacts. Similar results were found for a few injections made in the organum vasculosum of the lamina terminalis, just rostral to the MnPo, and in the immediately adjacent periventricular preoptic area. Coupled with other recent anatomical and electrophysiological evidence, these results suggest there is a strong monosynaptic pathway from structures along the ventral lamina terminalis to the supraoptic nucleus.

  1. Recombinant human erythropoietin offers neuroprotection through inducing endogenous erythropoietin receptor and neuroglobin in a neonatal rat model of periventricular white matter damage.

    PubMed

    Zhu, Lihua; Huang, Li; Wen, Quan; Wang, Ting; Qiao, Lixing; Jiang, Li

    2017-03-27

    Recombinant human erythropoietin (rh-EPO) has been reported to have protective effects against brain injury. The purpose of this study was to evaluate the levels of erythropoietin receptor (EPOR) and neuroglobin (Ngb) in a neonatal rat model of periventricular white matter damage (PWMD), and to identify the relationship between the two proteins. On postnatal day 3 (P3), rats underwent permanent ligation of the right common carotid artery followed by 6% O2 for 4h (HI) or sham operation and normoxic exposure (sham). Immediately after HI, rats received a single intraperitoneal injection of rh-EPO (5U/g) or saline. We assessed the expression level of Ngb and EPOR on postnatal days 5, 7, 10 and 14. EPOR in the HI rats was initially increased as compared to the sham rats at P5. Subsequently, EPOR expression decreased, but was maintained at a higher level than in sham rats from P7 to P14. In rh-EPO treated rats, the increase in EPOR was greater than in HI rats at P5. However, EPOR levels decreased sharply from P7 to P14. In HI rats, Ngb was increased compared to the sham rats from P5 to P14. Ngb levels were further upregulated after rh-EPO administration from P5 to P10 compared to HI rats. However, this upregulation decreased at P14. In conclusion, this study shows that EPOR and Ngb were upregulated, and both of them act as important coordinated neuroprotectors in rh-EPO treatment of PWMD. However, the two proteins exhibit different expression patterns.

  2. Calretinin Neurons in the Rat Suprachiasmatic Nucleus.

    PubMed

    Moore, Robert Y

    2016-08-01

    The hypothalamic suprachiasmatic nucleus (SCN), a circadian pacemaker, is present in all mammalian brains. It has a complex organization of peptide-containing neurons that is similar among species, but calcium-binding proteins are expressed variably. Neurons containing calretinin have been described in the SCN in a number of species but not with association to circadian function. The objective of the present study is to characterize a calretinin neuron (CAR) group in the rat anterior hypothalamus anatomically and functionally with a detailed description of its location and a quantitative analysis of neuronal calretinin immunoreactivity at 3 times of day, 0600, 1400, and 1900 h, from animals in either light-dark or constant dark conditions. CAR neurons occupy a region in the dorsal and lateral SCN with a circadian rhythm in CAR immunoreactivity with a peak at 0600 h and a rhythm in cytoplasmic CAR distribution with a peak at 1400 h. CAR neurons should be viewed as an anatomical and functional component of the rat SCN that expands the definition from observations with cell stains. CAR neurons are likely to modulate temporal regulation of calcium in synaptic transmission.

  3. Progress in periventricular leukomalacia.

    PubMed

    Deng, Wenbin; Pleasure, Jeanette; Pleasure, David

    2008-10-01

    Periventricular leukomalacia (PVL) is the predominant form of brain injury and the leading known cause of cerebral palsy and cognitive deficits in premature infants. The number of low-birth-weight infants who survive to demonstrate these neurologic deficts is increasing. Magnetic resonance imaging-based neuroimaging techniques provide greater diagnostic sensitivity for PVL than does head ultrasonography and often document the involvement of telencephalic gray matter and long tracts in addition to periventricular white matter. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia. Premyelinating oligodendroglia are highly vulnerable to death caused by glutamate, free radicals, and proinflammatory cytokines. Studies in animal models of PVL suggest that pharmacologic interventions that target these toxic molecules will be useful in diminishing the severity of PVL.

  4. Prophylactic ethamsylate for periventricular haemorrhage.

    PubMed Central

    Cooke, R W; Morgan, M E

    1984-01-01

    Drug prophylaxis with ethamsylate for periventricular haemorrhage in very low birthweight infants significantly reduced the incidence of periventricular haemorrhage in survivors. A reduction in abnormalities at follow up and in insertion of ventriculoperitoneal shunts was also noted. PMID:6696506

  5. Projections to the rostral reticular thalamic nucleus in the rat.

    PubMed

    Cornwall, J; Cooper, J D; Phillipson, O T

    1990-01-01

    Afferent pathways to the rostral reticular thalamic nucleus (Rt) in the rat were studied using anterograde and retrograde lectin tracing techniques, with sensitive immunocytochemical methods. The analysis was carried out to further investigate previously described subregions of the reticular thalamic nucleus, which are related to subdivisions of the dorsal thalamus, in the paraventricular and midline nuclei and three segments of the mediodorsal thalamic nucleus. Cortical inputs to the rostral reticular nucleus were found from lamina VI of cingulate, orbital and infralimbic cortex. These projected with a clear topography to lateral, intermediate and medial reticular nucleus respectively. Thalamic inputs were found from lateral and central segments of the mediodorsal nucleus to the lateral and intermediate rostral reticular nucleus respectively and heavy paraventricular thalamic inputs were found to the medial reticular nucleus. In the basal forebrain, afferents were found from the vertical and horizontal limbs of the diagonal band, substantia innominata, ventral pallidum and medial globus pallidus. Brainstem projections were identified from ventrolateral periaqueductal grey and adjacent sites in the mesencephalic reticular formation, laterodorsal tegmental nucleus, pedunculopontine nucleus, medial pretectum and ventral tegmental area. The results suggest a general similarity in the organisation of some brainstem Rt afferents in rat and cat, but also show previously unsuspected inputs. Furthermore, there appear to be at least two functional subdivisions of rostral Rt which is reflected by their connections with cortex and thalamus. The studies also extend recent findings that the ventral striatum, via inputs from the paraventricular thalamic nucleus, is included in the circuitry of the rostral Rt, providing further evidence that basal ganglia may function in concert with Rt. Evidence is also outlined with regard to the possibility that rostral Rt plays a significant

  6. Periventricular leukomalacia long-term prognosis may be improved by treatment with UDP-glucose, GDNF, and memantine in neonatal rats.

    PubMed

    Mao, Feng-Xia; Li, Wen-Juan; Chen, Hui-Jin; Qian, Long-Hua; Buzby, Jeffrey S

    2012-11-27

    The therapeutic effects of UDP-glucose (UDPG), an endogenous agonist of GPR17 that may promote the self-repair of white matter, glial cell line-derived neurotrophic factor (GDNF), a neurotrophic factor correlated with the growth and survival of nerve cells, and memantine, an antagonist of NMDA receptors, were evaluated for functional improvement of neonatal rats with experimental periventricular leukomalacia (PVL). Five day-old neonatal rat pups were subjected to an ischemia-induced model of PVL. The pups were then randomly divided into sham, PVL, PVL plus UDPG, PVL plus GDNF, and PVL plus memantine groups. All pups were weighed and the age at first eye opening recorded. Pathological changes and myelin sheath formation in the white matter were assessed under both light and electron microscopy on day 7 and 21 after induction of PVL. Values of escape latency (EL) and swimming distance (SD) in Morris water maze test, and the modified inclined plane scores in Rivlin inclined plane test were recorded for rats on day 26. Pups in the PVL group were found to be significantly lower in weight (p<0.05), delayed in age at first eye opening (p<0.01), and impaired in their inclined plane (p<0.01) and Morris water maze (p<0.01) performance compared with those in the sham, UDPG, GDNF and memantine groups. Histopathological grading of the white matter classified all pups in the PVL group with significantly more severe injury (p<0.01), and the number and thickness of their myelin sheaths were significantly less (p<0.01), compared to the UDPG, GDNF, memantine, or sham groups. These results indicate that treatment with UDPG, GDNF, and memantine may significantly improve long-term prognosis in neonatal rats with cerebral white matter injury, characteristic of PVL.

  7. Afferent projections to the deep mesencephalic nucleus in the rat

    SciTech Connect

    Veazey, R.B.; Severin, C.M.

    1982-01-10

    Afferent projections to the deep mesencephalic nucleus (DMN) of the rat were demonstrated with axonal transport techniques. Potential sources for projections to the DMN were first identified by injecting the nucleus with HRP and examining the cervical spinal cord, brain stem, and cortex for retrogradely labeled neurons. Areas consistently labeled were then injected with a tritiated radioisotope, the tissue processed for autoradiography, and the DMN examined for anterograde labeling. Afferent projections to the medial and/or lateral parts of the DMN were found to originate from a number of spinal, bulbar, and cortical centers. Rostral brain centers projecting to both medial and lateral parts of the DMN include the ipsilateral motor and somatosensory cortex, the entopeduncular nucleus, and zona incerta. at the level of the midbrain, the ipsilateral substantia nigra and contralateral DMN likewise project to the DMN. Furthermore, the ipsilateral superior colliculus projects to the DMN, involving mainly the lateral part of the nucleus. Afferents from caudal centers include bilateral projections from the sensory nucleus of the trigeminal complex and the nucleus medulla oblongata centralis, as well as from the contralateral dentate nucleus. The projections from the trigeminal complex and nucleus medullae oblongatae centralis terminate in the intermediate and medial parts of the DMN, whereas projections from the contralateral dentate nucleus terminate mainly in its lateral part. In general, the afferent connections of the DMN arise from diverse areas of the brain. Although most of these projections distribute throughout the entire extent of the DMN, some of them project mainly to either medial or lateral parts of the nucleus, thus suggesting that the organization of the DMN is comparable, at least in part, to that of the reticular formation of the pons and medulla, a region in which hodological differences between medial and lateral subdivisions are known to exist.

  8. Collateral projections from the lateral parabrachial nucleus to the paraventricular thalamic nucleus and the central amygdaloid nucleus in the rat.

    PubMed

    Liang, Shao-Hua; Yin, Jun-Bin; Sun, Yi; Bai, Yang; Zhou, Kai-Xiang; Zhao, Wen-Jun; Wang, Wei; Dong, Yu-Lin; Li, Yun-Qing

    2016-08-26

    Combined the retrograde double tracing with immunofluorescence histochemical staining, we examined the neurons in the lateral parabrachial nucleus (LPB) sent collateral projections to the paraventricular thalamic nucleus (PVT) and central amygdaloid nucleus (CeA) and their roles in the nociceptive transmission in the rat. After the injection of Fluoro-gold (FG) into the PVT and tetramethylrhodamine-dextran (TMR) into the CeA, respectively, FG/TMR double-labeled neurons were observed in the LPB. The percentages of FG/TMR double-labeled neurons to the total number of FG- or TMR-labeled neurons were 6.18% and 9.09%, respectively. Almost all of the FG/TMR double-labeled neurons (95%) exhibited calcitonin gene-related peptide (CGRP) immunoreactivity. In the condition of neuropathic pain, 94% of these neurons showed FOS immunoreactivity. The present data indicates that some of CGRP-expressing neurons in the LPB may transmit nociceptive information toward the PVT and CeA by way of axon collaterals.

  9. Nucleus incertus inactivation impairs spatial learning and memory in rats.

    PubMed

    Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh

    2015-02-01

    Nucleus incertus (NI) is a pontine nucleus which releases mainly GABA and relaxin-3 in rats. Its suggested functions include response to stress, arousal, and modulation of hippocampal theta rhythm. Since the role of NI in learning and memory has not been well characterized, therefore the involvement of this nucleus in spatial learning and memory and the aftermath hippocampal levels of c-fos and pCREB were evaluated. NI was targeted by implanting cannula in male rats. For reference memory, NI was inactivated by lidocaine (0.4 μl, 4%) at three stages of acquisition, consolidation and retrieval in Morris water maze paradigm. For working memory, NI was inactivated in acquisition and retrieval phases. Injection of lidocaine prior to the first training session of reference memory significantly increased the distance moved, suggesting that inactivation of NI delays acquisition in this spatial task. Inactivation also interfered with the retrieval phase of spatial reference memory, as the time in target quadrant for lidocaine group was less, and the escape latency was higher compared to the control group. However, no difference was observed in the consolidation phase. In the working memory task, with inter-trial intervals of 75 min, the escape latency was higher when NI was inactivated in the retrieval phase. In addition, c-fos and pCREB/CREB levels decreased in NI-inhibited rats. This study suggests that nucleus incertus might participate in acquisition of spatial reference, and retrieval of both spatial reference and working memory. Further studies should investigate possible roles of NI in the hippocampal plasticity.

  10. Genetics Home Reference: periventricular heterotopia

    MedlinePlus

    ... heterotopia is a condition in which nerve cells ( neurons ) do not migrate properly during the early development ... means "out of place." In normal brain development, neurons form in the periventricular region, located around fluid- ...

  11. Circadian modulation of osmoregulated firing in rat supraoptic nucleus neurones.

    PubMed

    Trudel, E; Bourque, C W

    2012-04-01

    The antidiuretic hormone vasopressin (VP) promotes water reabsorption from the kidney and levels of circulating VP are normally related linearly to plasma osmolality, aiming to maintain the latter close to a predetermined set point. Interestingly, VP levels rise also in the absence of an increase in osmolality during late sleep in various mammals, including rats and humans. This circadian rhythm is functionally important because the absence of a late night VP surge results in polyuria and disrupts sleep in humans. Previous work has indicated that the VP surge may be caused by facilitation of the central processes mediating the osmotic control of VP release, and the mechanism by which this occurs was recently studied in angled slices of rat hypothalamus that preserve intact network interactions between the suprachiasmatic nucleus (SCN; the biological clock), the organum vasculosum lamina terminalis (OVLT; the central osmosensory nucleus) and the supraoptic nucleus (SON; which contains VP-releasing neurohypophysial neurones). These studies confirmed that the electrical activity of SCN clock neurones is higher during the middle sleep period (MSP) than during the late sleep period (LSP). Moreover, they revealed that the excitation of SON neurones caused by hyperosmotic stimulation of the OVLT was greater during the LSP than during the MSP. Activation of clock neurones by repetitive electrical stimulation, or by injection of glutamate into the SCN, caused a presynaptic inhibition of glutamatergic synapses made between the axon terminals of OVLT neurones and SON neurones. Consistent with this effect, activation of clock neurones with glutamate also reduced the excitation of SON neurones caused by hyperosmotic stimulation of the OVLT. These results suggest that clock neurones in the SCN can mediate an increase in VP release through a disinhibition of excitatory synapses between the OVLT and the SON during the LSP. © 2012 The Authors. Journal of Neuroendocrinology © 2012

  12. Rats self-administer carbachol directly into the nucleus accumbens.

    PubMed

    Ikemoto, S; Glazier, B S; Murphy, J M; McBride, W J

    1998-03-01

    The potential reinforcing effect of the muscarinic cholinergic agonist carbachol within the nucleus accumbens (ACB) was examined in female Wistar rats by using the technique of intracranial self-administration. Rats dose dependently self-administered solutions of 0.0-6.6 mM (in a volume of 100 nL per injection) directly into the ACB. Rats self-administered the 3.3 and 6.6 mM doses significantly more than the group given only vehicle. The caudate putamen did not support reliable self-administration of the 6.6-mM dose. Rats exhibited preference for the lever that produced infusions of 3.3 and 6.6 mM carbachol into the ACB over the lever that had no consequence. The self-infusion of the 6.6-mM dose into the ACB was inhibited by the coadministration of the muscarinic antagonist scopolamine (0.25 mM), but not by the nicotinic antagonist mecamylamine (6.6 mM). The present results suggest that direct activation of muscarinic receptors within the ACB supports self-administration and could result from reinforcement or from elicitation of a novel stimulus.

  13. [Analgesic action of microinjection of neurokinin A into the lateral reticular nucleus and nucleus raphe magnus in rats].

    PubMed

    Yan, G P; Zhao, Y; Huang, Q E; Chen, W M

    1996-10-01

    Using the microinjection technique, the analgesic effect of neurokinin A (NKA) microinjected into the lateral reticular nucleus (LRN) and nucleus raphe magnus (NRM) was investigated in lightly pentobarbital-anesthetized rats using tail flick latency (TFL) as an index. Microinjection of NKA (0.5 microgram/0.5 microliter) into LRN significantly increased TFL lasting for 10 min (n = 12, P < 0.001). Microinjection of the same amount of NKA into NRM also produced evident increase in TFL for 5 min (n = 13, P < 0.001). The results indicate that NKA modulates pain reaction in both LRN and NRM in rats.

  14. Capsaicin augments synaptic transmission in the rat medial preoptic nucleus.

    PubMed

    Karlsson, Urban; Sundgren-Andersson, Anna K; Johansson, Staffan; Krupp, Johannes J

    2005-05-10

    The medial preoptic nucleus (MPN) is the major nucleus of the preoptic area (POA), a hypothalamic area involved in the regulation of body-temperature. Injection of capsaicin into this area causes hypothermia in vivo. Capsaicin also causes glutamate release from hypothalamic slices. However, no data are available on the effect of capsaicin on synaptic transmission within the MPN. Here, we have studied the effect of exogenously applied capsaicin on spontaneous synaptic activity in hypothalamic slices of the rat. Whole-cell patch-clamp recordings were made from visually identified neurons located in the MPN. In a subset of the studied neurons, capsaicin enhanced the frequency of spontaneous glutamatergic EPSCs. Remarkably, capsaicin also increased the frequency of GABAergic IPSCs, an effect that was sensitive to removal of extracellular calcium, but insensitive to tetrodotoxin. This suggests an action of capsaicin at presynaptic GABAergic terminals. In contrast to capsaicin, the TRPV4 agonist 4alpha-PDD did not affect GABAergic IPSCs. Our results show that capsaicin directly affects synaptic transmission in the MPN, likely through actions at presynaptic terminals as well as on projecting neurons. Our data add to the growing evidence that capsaicin receptors are not only expressed in primary afferent neurons, but also contribute to synaptic processing in some CNS regions.

  15. Hypoglossal nucleus projections to the rat masseter muscle.

    PubMed

    Mameli, O; Stanzani, S; Russo, A; Pellitteri, R; Spatuzza, M; Caria, M A; Mulliri, G; De Riu, P L

    2009-08-04

    We investigated in the rat whether hypoglossal innervation extended to facial muscles other than the extrinsic musculature of the mystacial pad. Results showed that hypoglossal neurons also innervate the masseter muscle. Dil injected into the XII nucleus showed hypoglossal axons in the ipsilateral main trunk of the trigeminal nerve. After Gasser's ganglion crossing, the axons entered into the infraorbital division of the trigeminal nerve and targeted the extrinsic muscles of the mystacial pad. They also spread into the masseter branch of the trigeminal nerve to target the polar portions of the masseter muscle spindles. Retrograde double labelling, performed by injecting Dil into the pad and True Blue into the ipsilateral masseter muscle, showed labelled hypoglossal neurons in the medio-dorsal portion of the XII nucleus. The majority of these neurons were small (15-20 microm diameter), showed fluorescence for Dil and projected to the mystacial pad. Other medium-size neurons (25 microm diameter) were instead labelled with True Blue and projected to the masseter muscle. Finally, in the same area, other small hypoglossal neurons showed double labelling and projected to both structures. Functional hypotheses on the role of these hypoglossal projections have been discussed.

  16. Preoptic-hypothalamic periventricular lesions: thirst deficits and hypernatremia.

    PubMed

    Buggy, J; Jonhson, A K

    1977-07-01

    To assess the significance of stimulation studies suggesting an anteroventral third ventricle (AV3V) dipsogenic site of action for hyperosmotic and angiotensin thirst stimuli, electrolytic lesions of periventricular tissue surrounding AV3V were produced under ether anesthesia in rats preselected for responsiveness to subcutaneous angiotensin and hypertonic NaCl thirst challenges. Lesions limited to preoptic-anterior hypothalamic periventricular substrates resulted in adipsia; those rats resuming ad lib. drinking after a period of adipsia exhibited persistent drinking deficits to angiotensin and hypertonic NaCl thirst challenges, reduced drinking after water deprivation, and increased plasma osmolality and sodium. Drinking to polyethylene glycol-induced hypovolemia and feeding after food deprivation did not differ between lesioned and sham-lesioned animals. The disturbances in behavioral control of fluid balance imply that AV3V periventricular tissue normally plays a key role in mediating regulatory drinking. It is proposed that these AV3V periventricular lesion-induced effects on drinking behavior are due to destruction of receptors and/or integrative systems monitoring fluid-borne angiotensin and hyperosmotic stimuli.

  17. Cortical connections of the rat lateral posterior thalamic nucleus.

    PubMed

    Kamishina, Hiroaki; Conte, William L; Patel, Sarika S; Tai, Rachel J; Corwin, James V; Reep, Roger L

    2009-04-06

    Spatial processing related to directed attention is thought to be mediated by a specific cortical-basal ganglia-thalamic-cortical network in the rat. Key components of this network are associative cortical areas medial agranular cortex (AGm) and posterior parietal cortex (PPC), dorsocentral striatum (DCS), and lateral posterior (LP) thalamic nucleus, all of which are interconnected. Previously, we found that thalamostriatal projections reaching DCS arise from separate populations of neurons of the mediorostral part of LP (LPMR). The far medial LPMR (fmLPMR) terminates in central DCS, a projection area of AGm, whereas central LPMR terminates in dorsal DCS, a projection area of PPC. This represents segregated regional convergence in DCS from different sources of thalamic and cortical inputs. In the present study, thalamocortical and corticothalamic projections arising from and terminating in LPMR and neighboring thalamic nuclei were studied by anterograde and retrograde tracing techniques in order to further understand the anatomical basis of this neural circuitry. A significant finding was that within LPMR, separate neuronal populations provide thalamic inputs to AGm or PPC and that these cortical areas project to separate regions in LPMR, from which they receive thalamic inputs. Other cortical areas adjacent to AGm or PPC also demonstrated reciprocal connections with LP or surrounding nuclei in a topographic manner. Our findings suggest that the cortical-basal ganglia-thalamic network mediating directed attention in the rat is formed by multiple loops, each having reciprocal connections that are organized in a precise and segregated topographical manner.

  18. [Extracellular aminoacids in the amygdala and nucleus accumbens in the rat during acute pain].

    PubMed

    Silva, Elizabeth; Hernández, Luis

    2007-06-01

    In the present experiments extracellular arginine, glutamate and aspartate were studied in the basolateral nucleus of the amygdala and core of the nucleus accumbens during the formalin test (phase I). A combination of capillary zone electrophoresis with laser induced fluorescence detection and microdialysis in freely moving rats was used. Glutamate and arginine significantly increased in the nucleus accumbens after formalin injection; glutamate, arginine and aspartate significantly increased in the basolateral nucleus of the amygdala, after formalin injection. These experiments suggest that rapid neurotransmitters changes observed in the nucleus accumbens and amygdala, are possibly related to immobility and emotional states such as anxiety, aversion and/or depression caused by pain.

  19. [Repeated exposure in hypergravity: morphology of locus coeruleus, hypothalamic paraventricular nucleus and vagal nerve dorsal nucleus in rats].

    PubMed

    Krasnov, I B; Fidelina, O V; Gorbatiuk, O S; Vikhreva, O V

    2000-01-01

    As compared to analogous single rotation at 2 g and in contrast to 5-d single and repeated exposures to Coriolis accelerations, repeated 5-day hypergravity (2 g generated by centrifuge rotation) gave rise to structural alterations in rat's neurons of locus coeruleus, vasopressinergic neurons of the lateral magnocellular subnucleus paraventricular nucleus and nervi vagi dorsal nucleus suggesting involvement of these structures of brain in the mechanism of facilitation of adaptation to repeated long-term hypergravity. Results of the study point to the ability of mammals to remember changes in gravity. Findings of the study may help develop an algorithm of intermittent exposure to artificial gravity aboard space vehicle.

  20. The effect of blockade of dopamine receptors on the inhibition of episodic luteinizing hormone release during electrical stimulation of the arcuate nucleus in ovariectomized rats.

    PubMed

    Gallo, R V

    1978-04-01

    This study examined the possible involvement of dopamine (DA) in mediating the inhibition of episodic LH release that occurs during electrical stimulation of the arcuate nucleus (ARH) in ovariectomized rats. Animals were treated before stimulation with pimozide (1.26--2.0 mg/kg) or d-butaclamol (1 mg/kg), blockers of DA receptors, or l-butaclamol. Apomorphine, which inhibits episodic LH release by activating DA receptors, was given near the end of the experiment to determine if these receptors were blocked. ARH stimulation suppressed pulsatile LH release in six rats when DA receptors were not blocked by pimozide (as well as two in which blockade was not tested). A transient increase occurred in one other animal. When DA receptors were blocked by pimozide, stimulation of the ARH inhibited episodic LH release in nine rats, suggesting that DA may have no role in mediating this inhibition. However, because increased LH release occurred in five additional animals, as well as in one with partial receptor blockade, the possibility remains that DA may perhaps have a minor role in this inhibitory response. Although ARH stimulation increased LH release after DA receptor blockade by d-butaclamol, this effect could not be ascribed to the DA antagonist property of this agent, because elevated blood LH levels also occurred during stimulation in rats treated with l-butaclamol, in which DA receptors were not blocked. d- and l-butaclamol may possess a non-stereospecific action on a non-dopaminergic event, thus reversing the response to ARH stimulation. Finally, whether DA receptors were blocked or not by pimozide, d-, or l-butaclamol, activation of the ventromedial hypothalamic and periventricular nucleus regions suppressed episodic LH release, but did not increase LH secretion. This suggests that the region through which stimulation can inhibit, but not increase, LH release may extend in the hypothalamus to these two areas.

  1. Effects of cytotoxic nucleus accumbens lesions on instrumental conditioning in rats.

    PubMed

    de Borchgrave, R; Rawlins, J N P; Dickinson, A; Balleine, B W

    2002-05-01

    In two experiments the involvement of the nucleus accumbens in instrumental conditioning was investigated using rats as subjects. In experiment 1, extensive bilateral cytotoxic lesions of the nucleus accumbens mildly suppressed instrumental responding reinforced with food, but had no detectable effect on the sensitivity of the rats' performance either to outcome devaluation or to degradation of the instrumental contingency. In experiment 2, restricted accumbens lesions reliably attenuated the excitatory effect of systemically administered d-amphetamine on lever pressing for a conditioned reinforcer, and completely abolished Pavlovian-instrumental transfer. Taken together these results give a picture of the involvement of the rat nucleus accumbens in instrumental conditioning. They support the widely held theory that the nucleus accumbens mediates the excitatory effects of appetitively conditioned Pavlovian signals on instrumental performance and refute the hypothesis that the nucleus accumbens is part of the neural circuitry by which incentive value is attached to the representations of instrumental outcomes.

  2. Effects of systemic L-tyrosine on dopamine release from rat corpus striatum and nucleus accumbens

    NASA Technical Reports Server (NTRS)

    During, Matthew J.; Acworth, Ian N.; Wurtman, Richard J.

    1988-01-01

    Intracerebral dialysis was used to monitor extracellular fluid from rat striatum and nucleus accumbens following the intraperitoneal administration of tyrosine. Dopamine concentrations in dialysates from both the striatum and the nucleus accumbens increased significantly in response to the tyrosine. The magnitude of the tyrosine effect was greater in the nucleus accumbens than in the striatum. Hence, mesolimbic dopaminergic neurons may be especially responsive to precursor availability.

  3. Modulation of hypothalamic arcuate nucleus on gastric motility in rats

    PubMed Central

    Xu, Guang-Yao; Ma, Rong; Cao, Qi; Su, Bao-Tian

    1998-01-01

    AIM: To investigate whether the arcuate nucleus (ARC) could modulate gastric motility, and if so, what are the mechanisms or pathways. METHODS: Wistar rats, anaesthetized with urethan, parameters of stimulation and electrolytic lesion sites were determined according to the Paxinos and Watson “ATLAS of rat brain in steriotaxic coordinate”. Intragastric pressure ( IGP ) and gastric motility were measured by Reybould¡äs method. RESULTS: Electrical stimulation of ARC could obviously decrease the IGP by 42.2% ± 5.4%, n = 15, P < 0.01, and the phasic gastric contractions disappeared. The analysis showed that the locus coeruleus (LC) and dorsal raphe (DR) nuclei may be involved in central, but without the invovement of β-endorphinergic neurons rich in the ARC, while in periphery, the peripheral neural pathways are both vagus and sympathetic nerves. The fibers in vagus may be non-cholinergic. Humoral factors may also be involved. At the receptor level, Tonic action of adrenergic nerve in the stomach is mainly inhibitory; β-receptors, which may be present on the stomach wall and mediate inhibition; and α-receptors, which come into play through vagus, mediate inhibition, but those present on the smooth muscle mediate sympathetic excitation. Microinjection of TRH into ARC could significantly increase the IGP by 183.02% (0.53 kPa ± 0.08 kPa vs 1.5 kPa ± 0.6 kPa, n = 10, P < 0.001), the rate and amplitude of phasic gastric contraction were also increased (3 cpm vs 6 cpm-8 cpm). The peripheral pathway of such excitatory effects were transmitted with cholinergic vagus nerve mediated by M-receptor. CONCLUSION: ARC could modulate gastric motility biphasically, inhibitory and excitatory, depending on the nature of stimuli. PMID:11819337

  4. Mapping of Kisspeptin Receptor mRNA in the Whole Rat Brain and its Co-Localisation with Oxytocin in the Paraventricular Nucleus.

    PubMed

    Higo, S; Honda, S; Iijima, N; Ozawa, H

    2016-04-01

    The neuropeptide kisspeptin and its receptor play an essential role in reproduction as a potent modulator of the gonadotrophin-releasing hormone (GnRH) neurone. In addition to its reproductive function, kisspeptin signalling is also involved in extra-hypothalamic-pituitary-gonadal (HPG) axis systems, including oxytocin and arginine vasopressin (AVP) secretion. By contrast to the accumulating information for kisspeptin neurones and kisspeptin fibres, the histological distribution and function of the kisspeptin receptor in the rat brain remain poorly characterised. Using in situ hybridisation combined with immunofluorescence, the present study aimed to determine the whole brain map of Kiss1r mRNA (encoding the kisspeptin receptor), and to examine whether oxytocin or AVP neurones express Kiss1r. Neurones with strong Kiss1r expression were observed in several rostral brain areas, including the olfactory bulb, medial septum, diagonal band of Broca and throughout the preoptic area, with the most concentrated population being around 0.5 mm rostral to the bregma. Co-immunofluorescence staining revealed that, in these rostral brain areas, the vast majority of the Kiss1r-expressing neurones co-expressed GnRH. Moderate levels of Kiss1r mRNA were also noted in the rostral periventricular area, paraventricular nucleus (PVN), and throughout the arcuate nucleus. Relatively weak Kiss1r expression was observed in the supraoptic nucleus and supramammillary nuclei. Moderate to weak expression of Kiss1r was also observed in several regions in the midbrain, including the periaqueductal gray and dorsal raphe nucleus. We also examined whether oxytocin and AVP neurones in the PVN co-express Kiss1r. Immunofluorescence revealed the co-expression of Kiss1r in a subset of the oxytocin neurones but not in the AVP neurones in the PVN. The present study provides a fundamental anatomical basis for further examination of the kisspeptin signalling system in the extra-HPG axis, as well as in

  5. A bushy cell network in the rat ventral cochlear nucleus

    PubMed Central

    Gomez-Nieto, Ricardo; Rubio, Maria E.

    2010-01-01

    Geometry of the dendritic tree and synaptic organization of afferent inputs are essential factors in determining how synaptic input is integrated by neurons. This information remains elusive for one of the first brainstem neurons involved in processing of the primary auditory signal from the ear, the bushy cells (BCs) of the ventral cochlear nucleus (VCN). Here, we labeled the BC dendritic trees with retrograde tracing techniques to analyze their geometry and synaptic organization after immunofluorescence for excitatory and inhibitory synaptic markers, electron microscopy, morphometry, double tract-tracing methods, and 3-D reconstructions. Our study revealed that BC dendrites provide space for a large number of compartmentalized excitatory and inhibitory synaptic interactions. The dendritic inputs on BCs are of cochlear and non-cochlear origin, and their proportion and distribution are dependent on the branching pattern and orientation of the dendritic tree in the VCN. Three-dimensional reconstructions showed that BC dendrites branch and cluster with those of other BCs in the core of the VCN. Within the cluster, incoming synaptic inputs establish divergent multiple-contact synapses (dyads and triads) between BCs. Furthermore, neuron-neuron connections including puncta adherentia, sarcoplasmic junctions and gap junctions are common between BCs, which suggests that these neurons are electrically coupled. Together, our study demonstrates the existence of a BC network in the rat VCN. This network may establish the neuroanatomical basis for acoustic information processing by individual BCs, as well as for enhanced synchronization of the output signal of the VCN. PMID:19634178

  6. Comparison of neuronal activities of external cuneate nucleus, spinocerebellar cortex and interpositus nucleus during passive movements of the rat's forelimb.

    PubMed

    Casabona, A; Valle, M S; Bosco, G; Perciavalle, V

    2008-11-11

    In this paper we examined the neuronal activities of external cuneate nucleus, spinocerebellar Purkinje cells and interpositus nucleus during passive forelimb movements in anesthetized rats with the aim of identifying common or different patterns of activation across structures. By means of principal components analysis, we identified two main patterns of discharge which explained most of the dataset variance. One component characterized the movement-related activity of external cuneate and spinocerebellar cortical neurons, while the other reflected neuronal activity of the interpositus nucleus. We also found that both principal components were related to global forelimb kinematics but, while most of the variance of the activity of external cuneate cells and spinocerebellar Purkinje cells was explained by the limb axis orientation and orientation velocity, interpositus neurons' firing was best related to length and length velocity. This difference in the forelimb kinematics representation observed in external cuneate nucleus and spinocerebellar cortex compared with the interpositus nucleus is discussed with respect to the specific role that these structures may play also during active control of limb movements.

  7. Hemimegaloencephaly with periventricular heterotopia--case report.

    PubMed

    Sugiyama, S; Fujii, M; Nomura, S; Yamashita, T; Ito, H; Hayashi, T

    1994-08-01

    A 7-year-old girl was admitted with an unusual anomaly of hemimegaloencephaly associated with periventricular heterotopia manifesting as intractable seizures and mental retardation. Magnetic resonance (MR) imaging showed left hemispheric hypertrophy and left ventricular dilatation. Proton density-weighted MR imaging revealed a periventricular lesion isointense with gray matter. MR imaging is an effective method for diagnosing hemimegaloencephaly and heterotopia.

  8. Periventricular leukomalacia is decreasing in Japan.

    PubMed

    Sugiura, Tokio; Goto, Tatenobu; Ueda, Hiroko; Ito, Koichi; Kakita, Hiroki; Nagasaki, Rika; Mizuno, Keisuke; Suzuki, Satoshi; Kato, Ineko; Togari, Hajime

    2012-07-01

    Periventricular leukomalacia is recognized as the leading cause of cerebral palsy in preterm infants. To clarify the prevalence of periventricular leukomalacia and cerebral palsy in Japan, a nationwide survey was performed. The prevalence of periventricular leukomalacia in the group of surviving preterm infants of gestational ages less than 33 weeks born in 2007 was 2.7% (78/2883) on ultrasound diagnosis, and 3.3% (92/2824) on magnetic resonance imaging. The prevalence of cerebral palsy was 4.3% (125/2883) on clinical diagnosis. In our previous study, the prevalences of periventricular leukomalacia in 1990-1991, 1993-1994, 1996, and 1999 were 4.8%, 4.9%, 4.9%, and 5.3% on ultrasound, and 7.9%, 7.7%, 6.9%, and 7.3% on magnetic resonance imaging, respectively. The prevalence of periventricular leukomalacia has decreased significantly in Japan.

  9. Sexual dimorphism in the parastrial nucleus of the rat preoptic area.

    PubMed

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

    1990-03-01

    This work investigates the possible existence of sex differences in the volume of the parastrial nucleus (PSN), a component of the preoptic area in the rat. The effects of postnatal (on day 1 after birth) male orchidectomy and female androgenization on this nucleus were studied. The volume of the PSN was greater in the control females than in the control males and postnatal treatments reversed this sexual dimorphism.

  10. A light and electron microscope study of rat abducens nucleus neurons projecting to the cerebellar flocculus.

    PubMed Central

    Rodella, L; Rezzani, R; Corsetti, G; Simonetti, C; Stacchiotti, A; Ventura, R G

    1995-01-01

    Injection of horseradish peroxidase (HRP) into the cerebellar flocculus of the rat was employed to identify neurons in the abducens nucleus that project to the flocculus. The number, ultrastructural features and precise localisation of these neurons in the nucleus were examined. They were present bilaterally and represented about 7% of the total neuronal population of each nucleus. They were localised principally in the dorsomedial area of the cranial half of each nucleus and did not display the typical ultrastructural features of motoneurons. It is concluded that the localisation and ultrastructural characteristics of these HRP-positive neurons are useful for distinguishing them from other neuronal populations within the nucleus. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:7649835

  11. Synaptic endfeet in the 'acoustic nerve nucleus' of the rat. An electron microscopic study.

    PubMed Central

    Alvarez-Bolado, G; Merchán, J

    1988-01-01

    The medial portion of the cochlear nerve of the rat contains astrocytes, oligodendrocytes and neurons. These neurons form what has been called the 'acoustic nerve nucleus'. This nucleus has been studied here at the electron microscopic level. Its neurons are large and round, showing an eccentric nucleus, fibrillary bodies and rough endoplasmic reticulum which is not arranged in stacks. The somata and dendrites receive synaptic endfeet which can be classified into three groups according to vesicle size and shape. In general, the ultrastructural characteristics of these cells are similar to those of bushy cells as reported by other authors. The 'acoustic nerve nucleus' can be considered to be the most peripheral part of the anterior ventral cochlear nucleus. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:3248967

  12. Intracranial self-stimulation in the parafascicular nucleus of the rat.

    PubMed

    Vale-Martínez, A; Guillazo-Blanch, G; Aldavert-Vera, L; Segura-Torres, P; Martí-Nicolovius, M

    1999-03-01

    A behavioral analysis of intracranial self-stimulation was provided for parafascicular nucleus. To evaluate whether intracranial self-stimulation in this nucleus could be site-specific and to determine if the positive sites are the same parafascicular areas that facilitate learning when stimulated, rats were tested via monopolar electrodes situated throughout the parafascicular nucleus. Animals were trained to self-stimulate by pressing a lever in a conventional Skinner box (1-5 sessions). Twenty-two of the 42 animals included in the study, had the electrode at the parafascicular nucleus. Only two of them showed intracranial self-stimulation. Histological analyses indicated that the latter rats had the electrode implanted at the anterior area of the medial parafascicular. Other two animals also showed intracranial self-stimulation but they had the electrode in a more posterior brain region, between the Dark-schewitsch nucleus and the red nucleus. The animals implanted at the parafascicular showed higher response rates than the other two rats. These results confirm that: (a) the anterior region of the medial parafascicular is a positive site for stable and regular intracranial self-stimulation behavior, and (b) these positive sites do not coincide with the parafascicular regions related to learning improvement.

  13. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    PubMed

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens.

  14. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats

    PubMed Central

    Salti, Ahmad; Kummer, Kai K.; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2016-01-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

  15. Expression of gastrointestinal nesfatin-1 and gastric emptying in ventromedial hypothalamic nucleus- and ventrolateral hypothalamic nucleus-lesioned rats.

    PubMed

    Tian, Zi-Bin; Deng, Run-Jun; Sun, Gui-Rong; Wei, Liang-Zhou; Kong, Xin-Juan; Ding, Xue-Li; Jing, Xue; Zhang, Cui-Ping; Ge, Yin-Lin

    2014-06-14

    To determine the expression levels of gastrointestinal nesfatin-1 in ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imbalance in their energy metabolism and gastric mobility. Male Wistar rats were randomly divided into a VMH-lesioned group, a VLH-lesioned group, and their respective sham-operated groups. The animals had free access to food and water, and their diets and weights were monitored after surgery. Reverse transcription-polymerase chain reaction and immunostaining were used to analyse the levels of NUCB2 mRNA and nesfatin-1 immunoreactive (IR) cells in the stomach, duodenum, small intestine, and colon, respectively. Gastric emptying was also assessed using a modified phenol red-methylcellulose recovery method. The VMH-lesioned rats fed normal chow exhibited markedly greater food intake and body weight gain, whereas the VLH-lesioned rats exhibited markedly lower food intake and body weight gain. NUCB2/nesfatin-1 IR cells were localised in the lower third and middle portion of the gastric mucosal gland and in the submucous layer of the enteric tract. Compared with their respective controls, gastric emptying was enhanced in the VMH-lesioned rats (85.94% ± 2.27%), whereas the VLH lesions exhibited inhibitory effects on gastric emptying (29.12% ± 1.62%). In the VMH-lesioned rats, the levels of NUCB2 mRNA and nesfatin-1 protein were significantly increased in the stomach and duodenum and reduced in the small intestine. In addition, the levels of NUCB2 mRNA and nesfatin-1 protein in the VLH-lesioned rats were decreased in the stomach, duodenum, and small intestine. Our study demonstrated that nesfatin-1 level in the stomach and duodenum is positively correlated with body mass. Additionally, there is a positive relationship between gastric emptying and body mass. The results of this study indicate that gastrointestinal nesfatin-1 may play a significant role in gastric

  16. The Suprachiasmatic Nucleus Modulates the Sensitivity of Arcuate Nucleus to Hypoglycemia in the Male Rat.

    PubMed

    Herrera-Moro Chao, D; León-Mercado, L; Foppen, E; Guzmán-Ruiz, M; Basualdo, M C; Escobar, C; Buijs, R M

    2016-09-01

    The suprachiasmatic nucleus (SCN) and arcuate nucleus (ARC) have reciprocal connections; catabolic metabolic information activates the ARC and inhibits SCN neuronal activity. Little is known about the influence of the SCN on the ARC. Here, we investigated whether the SCN modulated the sensitivity of the ARC to catabolic metabolic conditions. ARC neuronal activity, as determined by c-Fos immunoreactivity, was increased after a hypoglycemic stimulus by 2-deoxyglucose (2DG). The highest ARC neuronal activity after 2DG was found at the end of the light period (zeitgeber 11, ZT11) with a lower activity in the beginning of the light period (zeitgeber 2, ZT2), suggesting the involvement of the SCN. The higher activation of ARC neurons after 2DG at ZT11 was associated with higher 2DG induced blood glucose levels as compared with ZT2. Unilateral SCN-lesioned animals, gave a mainly ipsilateral activation of ARC neurons at the lesioned side, suggesting an inhibitory role of the SCN on ARC neurons. The 2DG-induced counterregulatory glucose response correlated with increased ARC neuronal activity and was significantly higher in unilateral SCN-lesioned animals. Finally, the ARC as site where 2DG may, at least partly, induce a counterregulatory response was confirmed by local microdialysis of 2DG. 2DG administration in the ARC produced a higher increase in circulating glucose compared with 2DG administration in surrounding areas such as the ventromedial nucleus of the hypothalamus (VMH). We conclude that the SCN uses neuronal pathways to the ARC to gate sensory metabolic information to the brain, regulating ARC glucose sensitivity and counterregulatory responses to hypoglycemic conditions.

  17. Tuberomammillary nucleus activation anticipates feeding under a restricted schedule in rats.

    PubMed

    Inzunza, O; Serón-Ferré, M J; Bravo, H; Torrealba, F

    2000-10-27

    We used FOS-immunoreactivity to map changes in the neuronal activity of brain nuclei related to the state of arousal, in rats under a restricted feeding schedule. Our main finding was the outstanding activation of the tuberomammillary nucleus 24h after a meal, and its steep deactivation, which was independent of actually having the meal. The time course of FOS activation and deactivation indicated a burst of tuberomammilary nucleus activity in close temporal relation with the increased locomotor activity shown by rats in anticipation of the next meal.

  18. Sexual activity increases dopamine transmission in the nucleus accumbens and striatum of female rats.

    PubMed

    Pfaus, J G; Damsma, G; Wenkstern, D; Fibiger, H C

    1995-09-25

    In vivo microdialysis was used to monitor extracellular concentrations of dopamine (DA), and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and dorsal striatum of sexually active female rats during tests of locomotor activity, exposure to a novel chamber, exposure to sex odors, the presentation of a sexually active male rat, and copulation. DA increased slightly but significantly in the nucleus accumbens when a sexually active male was placed behind a wire-mesh screen, and further during copulation. DA also increased significantly in the dorsal striatum during copulation; however, the magnitude of this effect was significantly lower than that observed in the nucleus accumbens. The metabolites DOPAC and HVA generally followed DA with a delay, and increased significantly during copulation in both regions. In contrast, forced locomotion on a rotating drum, exposure to a novel testing chamber, and exposure to sex odors did not increase DA significantly in either region, although forced locomotion increased DOPAC significantly in both regions, and HVA significantly in the nucleus accumbens. The magnitude of DA release in the nucleus accumbens was significantly greater during copulation than running, whereas no significant difference was detected for striatal DA release between these two behavioral conditions. These results indicate that novelty or locomotor activity alone do not account for the increase in DA observed in the nucleus accumbens of female rats during copulation, and suggest that DA transmission in the nucleus accumbens is associated with anticipatory and consummatory aspects of sexual activity, as it is in male rats. In the dorsal striatum, however, DA release during copulation may reflect an increase in locomotor activity associated with active pacing of the male.

  19. Periventricular leukomalacia in a neonatal calf

    PubMed Central

    KOYAMA, Kenji; FUJITA, Riku; MAEZAWA, Masaki; FUKUMOTO, Natsuko; HORIUCHI, Noriyuki; INOKUMA, Hisashi; KOBAYASHI, Yoshiyasu

    2016-01-01

    A 10-day-old, Japanese Black, female calf had shown astasia since just after birth. Focal symmetrical periventricular malacic lesions of the cerebrum and suppurative arthritis of the left hip joint were observed in macroscopic examination. Histologically, the cerebral lesions were confirmed as periventricular leukomalacia (PVL). The location and histological features of the lesions were similar to PVL in humans, caused by neonatal ischemia/hypovolemia. This is the first report of PVL in a neonatal calf. PMID:27010465

  20. Muscarinic antagonists microinjected into the subthalamic nucleus decrease muscular rigidity in reserpinized rats.

    PubMed

    Hernández-López, S; Flores, G; Rosales, M G; Sierra, A; Martínez-Fong, D; Aceves, J

    1996-08-09

    The ability of anticholinergic agents microinjected into the subthalamic nucleus to reduce reserpine-induced muscular rigidity was assessed in rats. The electromyographical activity of the gastrocnemius-soleus muscle was used as a parameter of muscular rigidity. Reserpine (5 mg/kg i.p.) produced the appearance of electromyographical activity. The muscarinic antagonists M3 (1.27 nmol of 4-DAMP) and M1 (2.36 nmol of pirenzepine) markedly reduced the reserpine-induced electromyographical activity, whereas the M2 antagonist AFDX-116 (2.37 nmol) had no effect. These results suggest that a high cholinergic tone in the subthalamic nucleus is associated with the reserpine-induced muscular rigidity. Moreover, the M3 muscarinic antagonist is more effective than the M1 muscarinic antagonist in reducing the muscular rigidity in reserpinized rats, a model of Parkinson's disease, by blocking the high cholinergic tone in the subthalamic nucleus.

  1. The Role of the Nucleus Basalis Magnocellularis in Fear Conditioning Consolidation in the Rat

    ERIC Educational Resources Information Center

    Baldi, Elisabetta; Mariottini, Chiara; Bucherelli, Corrado

    2007-01-01

    The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear…

  2. Immunohistochemical localization of ionotropic glutamate receptors in the rat red nucleus

    PubMed Central

    Minbay, Zehra; Kocoglu, Sema Serter; Yurtseven, Duygu Gok; Eyigor, Ozhan

    2017-01-01

    In this study, we aimed to determine the presence as well as the diverse distribution of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor subunits in the rat red nucleus. Using adult Sprague-Dawley rats as the experimental animals, immunohistochemistry was performed on 30 µm thick coronal brain sections with antibodies against α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (GluA1-4), kainate (GluK1, GluK2/3, and GluK5), and NMDA (GluN1 and GluN2A) receptor subunits. The results showed that all ionotropic glutamate receptor subunits are expressed in the red nucleus. Specific staining was localized in the neuron bodies and processes. However, the pattern of immunoreactivity and the number of labeled neurons changed depending on the type of ionotropic glutamate receptor subunits and the localization of neurons in the red nucleus. The neurons localized in the magnocellular part of the red nucleus were particularly immunopositive for GluA2, GluA4, GluK2/3, GluK5, GluN1, and GluN2A receptor proteins. In the parvocellular part of the red nucleus, ionotropic glutamate receptor subunit immunoreactivity of variable intensity (lightly to moderately stained) was detected in the neurons. These results suggest that red nucleus neurons in rat heterogeneously express ionotropic glutamate receptor subunits to form functional receptor channels. In addition, the likelihood of the coexpression of different subunits in the same subgroup of neurons suggests the formation of receptor channels with diverse structure by way of different subunit combination, and the possibility of various neuronal functions through these channels in the red nucleus. PMID:28027456

  3. Immunohistochemical localization of ionotropic glutamate receptors in the rat red nucleus.

    PubMed

    Minbay, Zehra; Serter Kocoglu, Sema; Gok Yurtseven, Duygu; Eyigor, Ozhan

    2017-02-21

    In this study, we aimed to determine the presence as well as the diverse distribution of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor subunits in the rat red nucleus. Using adult Sprague-Dawley rats as the experimental animals, immunohistochemistry was performed on 30 µm thick coronal brain sections with antibodies against α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (GluA1-4), kainate (GluK1, GluK2/3, and GluK5), and NMDA (GluN1 and GluN2A) receptor subunits. The results showed that all ionotropic glutamate receptor subunits are expressed in the red nucleus. Specific staining was localized in the neuron bodies and processes. However, the pattern of immunoreactivity and the number of labeled neurons changed depending on the type of ionotropic glutamate receptor subunits and the localization of neurons in the red nucleus. The neurons localized in the magnocellular part of the red nucleus were particularly immunopositive for GluA2, GluA4, GluK2/3, GluK5, GluN1, and GluN2A receptor proteins. In the parvocellular part of the red nucleus, ionotropic glutamate receptor subunit immunoreactivity of variable intensity (lightly to moderately stained) was detected in the neurons. These results suggest that red nucleus neurons in rat heterogeneously express ionotropic glutamate receptor subunits to form functional receptor channels. In addition, the likelihood of the coexpression of different subunits in the same subgroup of neurons suggests the formation of receptor channels with diverse structure by way of different subunit combination, and the possibility of various neuronal functions through these channels in the red nucleus.

  4. Differential Fos expression in the paraventricular nucleus of the hypothalamus, sacral parasympathetic nucleus and colonic motor response to water avoidance stress in Fischer and Lewis rats.

    PubMed

    Million, M; Wang, L; Martinez, V; Taché, Y

    2000-09-22

    The responsiveness of hypothalamic CRF to various stressors is reduced in the young female Lewis relative to the histocompatible Fischer rat. Whether such a difference impacts the brain-gut response to water avoidance stress was investigated by monitoring Fos immunoreactivity in the brain and sacral spinal cord and fecal pellet output. Exposure for 60 min to water avoidance stress increased the number of Fos positive cells in the paraventricular nucleus of the hypothalamus (PVN), nucleus tractus solitarius (NTS), and the parasympathetic nucleus of the lumbo-sacral spinal cord (L6-S1) in both Lewis and Fischer rats compared with non stress groups. The Fos response was lower by 32.0% in the PVN, and 63% in sacral parasympathetic nucleus in Lewis compared with Fischer rats while similar Fos expression was observed in the NTS. Stress-induced defecation was reduced by 52% in Lewis compared with Fischer rats while colonic motor response to CRF injected intracisternally resulted in a similar pattern and magnitude of defecation in both strains. The CRF receptor antagonist [D-Phe12,Nle(21,38)C(a)MeLeu(37)]-CRF(12-41) injected intracisternally antagonized partly the defecation response in Lewis and Fischer rats. These data indicate that a lower activation of PVN and sacral parasympathetic nuclei in Lewis compared with Fisher rats may contribute to the differential colonic motor response and that the blunted CRF hypothalamic response to stress, unlike responsiveness to central CRF plays a role.

  5. Activation of c-fos expression in the rat inferior olivary nucleus by ghrelin.

    PubMed

    Zhang, Weizhen; Lin, Theodore R; Hu, Yuexian; Fan, Yongyi; Zhao, Lili; Mulholland, Michael W

    2003-12-26

    Ghrelin, a novel 28-amino-acid hormone secreted by gastric oxyntic glands, stimulates food intake and induces adiposity. We examined whether ghrelin activates the inferior olivary nucleus. Systemic administration of ghrelin (37 nmol/kg) induced the expression of c-fos immunoreactivity in inferior olive neurons (n=6 rats). The number of neurons containing c-fos staining was significantly increased in the ghrelin-treated rats (65+/-14 vs.11+/-6 positive neurons, n=5). No significant difference in c-fos-positive neurons was observed between left (32+/-5) and right (33+/-6) inferior olivary nuclei. The number of c-fos-positive neurons in rats with bilateral vagotomy was not significantly different from those with intact vagal nerves. The present study demonstrates that ghrelin induces c-fos expression in inferior olivary nucleus via a central mechanism.

  6. Isoperiodic neuronal activity in suprachiasmatic nucleus of the rat

    NASA Technical Reports Server (NTRS)

    Miller, J. D.; Fuller, C. A.

    1992-01-01

    A subpopulation of neurons in the suprachiasmatic nucleus (SCN) is shown here to exhibit isoperiodic bursting activity. The period of discharge in these cells may be lengthened or the periodicity may be transiently disrupted by photic stimulation. It is suggested that many, if not all, of these cells are vasoactive intestinal polypeptide (VIP) neurons. It is shown that the ultradian periodicity of these cells, estimates of the VIP neuron population size in the SCN, effects of partial lesions on tau (period), and estimates of the phase stability of SCN-driven circadian rhythms are consistent with a strongly coupled, multioscillator model of circadian rhythmicity, in which the oscillator population constitutes a restricted subset of the SCN neuronal population.

  7. Isoperiodic neuronal activity in suprachiasmatic nucleus of the rat

    NASA Technical Reports Server (NTRS)

    Miller, J. D.; Fuller, C. A.

    1992-01-01

    A subpopulation of neurons in the suprachiasmatic nucleus (SCN) is shown here to exhibit isoperiodic bursting activity. The period of discharge in these cells may be lengthened or the periodicity may be transiently disrupted by photic stimulation. It is suggested that many, if not all, of these cells are vasoactive intestinal polypeptide (VIP) neurons. It is shown that the ultradian periodicity of these cells, estimates of the VIP neuron population size in the SCN, effects of partial lesions on tau (period), and estimates of the phase stability of SCN-driven circadian rhythms are consistent with a strongly coupled, multioscillator model of circadian rhythmicity, in which the oscillator population constitutes a restricted subset of the SCN neuronal population.

  8. Characterization of a folate-induced hypermotility response after bilateral injection into the rat nucleus accumbens

    SciTech Connect

    Stephens, R.L. Jr.

    1986-01-01

    The objective of these studies was to pharmacologically characterize the mechanism responsible for a folate-induced stimulation of locomotor activity in rats after bilateral injection into the nucleus accumbens region of the brain. Folic acid (FA) and 5-formyltetrahydrofolic acid (FTHF) produced this hypermotility response after intra-accumbens injection, while other reduced folic acid derivatives dihydrofolic acid, tetrahydrofolic acid, and 5-methyltetrahydrofolic acid were ineffective. Studies were designed to determine the role of catecholamines in the nucleus accumbens in the folate-induced hypermotility response. The findings suggest that the folate-induced response is dependent on intact neuronal dopamine stores, and is mediated by stimulation of dopamine receptors of the nucleus accumbens. However the folates do not appear to enhance dopaminergic neutransmission. Thus, FA and FTHF were inefficient at 1 mM concentrations in stimulating /sup 3/H-dopamine release from /sup 3/H-dopamine preloaded nucleus accumbens slices or dopamine from endogenous stores. Pteroic acid, the chemical precursor of folic acid which lacks the glutamate moiety, was ineffective in producing a stimulation of locomotor activity after intra-accumbens injection. Since glutamate is an excitatory amino acid (EAA), compounds characterized as EAA receptor antagonists were utilized to determine if the folate-induced hypermotility response is mediated by activation of EAA receptors in the nucleus accumbens. These results suggest that activation of quisqualate receptors of the nucleus accumbens may mediate the folate-induced hypermotility response.

  9. Excitant amino acid projections from rat amygdala and thalamus to nucleus accumbens

    SciTech Connect

    Robinson, T.G.; Beart, P.M.

    1988-04-01

    High affinity uptake of D-(/sup 3/H)aspartate, (/sup 3/H)choline and (/sup 3/H)GABA was examined in synaptosomal-containing preparations of rat nucleus accumbens septi 7 to 10 days after unilateral or bilateral N-methyl-D-aspartate lesions confined to the parataenial nucleus of the thalamus or the basolateral nucleus of the amygdala. Uptake of both D-(/sup 3/H)aspartate and (/sup 3/H)choline was significantly reduced (11% and 14% less than control, respectively) by unilateral lesion of the thalamus, whereas (/sup 3/H)GABA uptake was unaffected. Bilateral thalamic lesions significantly reduced D-(/sup 3/H)aspartate uptake (11% less than control) into homogenates of the nucleus accumbens, whilst (/sup 3/H)GABA uptake was unaltered. D-(/sup 3/H)aspartate uptake was significantly reduced (26% less than control) following unilateral lesion of the amygdala, whereas both (/sup 3/H)GABA and (/sup 3/H)choline uptake were unaffected. Bilateral amygdaloid lesions significantly increased D-(/sup 3/H)aspartate uptake (39% greater than control), whilst uptake of (/sup 3/H)GABA was not affected. The results implicate glutamate and/or aspartate as putative neurotransmitters in afferent projections from the basolateral amygdala and the parataenial thalamus to the nucleus accumbens. Thalamic afferents to the nucleus accumbens may also utilize acetylcholine as their transmitter.

  10. Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats.

    PubMed

    Sclafani, A; Azzara, A V; Touzani, K; Grigson, P S; Norgren, R

    2001-08-01

    Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor + taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available.

  11. Cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus in the rat: role of the hypothalamic paraventricular nucleus.

    PubMed

    Kawabe, Tetsuya; Kawabe, Kazumi; Sapru, Hreday N

    2012-01-01

    The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP) close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA). The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA), neuropeptide Y (NPY), or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN). Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4) receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR) revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67), NPY, and beta-endorphin. These results indicated that: 1) at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2) lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3) at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.

  12. Immunohistochemical study of neurons in the rat abducens nucleus that project to the flocculus.

    PubMed Central

    Rodella, L; Rezzani, R; Bianchi, R

    1996-01-01

    The neurons of the rat abducens nucleus that project to the flocculus of the cerebellum were studied by double labelling using the retrograde transport of horseradish peroxidase (HRP) and choline acetyltransferase (ChAT) immunohistochemistry. Double-labelled cells were present bilaterally in the dorsal and dorsomedial zones of the cranial pole of the nucleus. They represented about half of the total number of HRP-positive neurons. These findings show the existence of a bilateral projection from the abducens nucleus to the flocculus which uses acetylcholine as a neurotransmitter. This projection could be part of the system of the nerve circuits through which the cerebellum modulates visual activities. Images Fig. 3 Fig. 4 Fig. 5 PMID:8763489

  13. Diurnal rhythm of melatonin binding in the rat suprachiasmatic nucleus

    SciTech Connect

    Laitinen, J.T.; Castren, E.; Vakkuri, O.; Saavedra, J.M.

    1989-03-01

    We used quantitative in vitro autoradiography to localize and characterize 2-/sup 125/I-melatonin binding sites in the rat suprachiasmatic nuclei in relation to pineal melatonin production. In a light:dark cycle of 12:12 h, binding density exhibited significant diurnal variation with a peak at the dark-light transition and a trough 12 hours later. Saturation studies suggested that the decreased binding at light-dark transition might be due to a shift of the putative melatonin receptor to a low affinity state.

  14. Ceftriaxone attenuates acute cocaine‐evoked dopaminergic neurotransmission in the nucleus accumbens of the rat

    PubMed Central

    Rasmussen, B A; Tallarida, C S; Scholl, J L; Forster, G L; Unterwald, E M; Rawls, S M

    2015-01-01

    Background and Purpose Ceftriaxone is a β‐lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine‐evoked dopaminergic neurotransmission in the nucleus accumbens. Experimental Approach Adult male Sprague–Dawley rats were pretreated with saline or ceftriaxone (200 mg kg−1, i.p. × 10 days) and then challenged with cocaine (15 mg kg−1, i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as α‐synuclein, Akt and GSK3β were analysed in the nucleus accumbens. Key Results Ceftriaxone‐pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline‐pretreated controls challenged with cocaine. The reduction in cocaine‐evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3β signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated α‐synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. Conclusions and Implications These results are the first evidence that ceftriaxone affects cocaine‐evoked dopaminergic transmission, in addition to its well‐described effects on glutamate, and suggest that its ability to attenuate cocaine‐induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens. PMID:26375494

  15. Ceftriaxone attenuates acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens of the rat.

    PubMed

    Barr, J L; Rasmussen, B A; Tallarida, C S; Scholl, J L; Forster, G L; Unterwald, E M; Rawls, S M

    2015-11-01

    Ceftriaxone is a β-lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens. Adult male Sprague-Dawley rats were pretreated with saline or ceftriaxone (200 mg kg(-1) , i.p. × 10 days) and then challenged with cocaine (15 mg kg(-1) , i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as α-synuclein, Akt and GSK3β were analysed in the nucleus accumbens. Ceftriaxone-pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline-pretreated controls challenged with cocaine. The reduction in cocaine-evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3β signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated α-synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. These results are the first evidence that ceftriaxone affects cocaine-evoked dopaminergic transmission, in addition to its well-described effects on glutamate, and suggest that its ability to attenuate cocaine-induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens. © 2015 The British Pharmacological Society.

  16. Autoregulation of dopamine synthesis in subregions of the rat nucleus accumbens.

    PubMed

    Heidbreder, C A; Baumann, M H

    2001-01-05

    The discovery of a core-shell dichotomy within the nucleus accumbens has opened new lines of investigation into the neuronal basis of psychiatric disorders and drug dependence. In the present study, the autoregulation of dopamine synthesis in subdivisions of the rat nucleus accumbens was examined. We measured the accumulation of L-3,4-dihydroxyphenylalanine (DOPA) after the inhibition of aromatic L-amino acid decarboxylase with 3-hydroxylbenzylhydrazine (NSD-1015, 100 mg kg(-1)) as an in vivo index of dopamine synthesis. The effect of the dopamine D(1)/D(2) receptor agonist apomorphine (0, 20, 100, 500 microgram kg(-1)) and the dopamine D(2)/D(3) receptor agonist quinpirole (0, 20, 100, 500 microgram kg(-1)) on dopamine synthesis was determined in the dorsolateral core, ventromedial shell, and rostral pole of the nucleus accumbens. DOPA accumulation was also measured in the frontal cortex, olfactory tubercle, and caudate nucleus of the same rats for comparative purposes. The results show that the three sectors of the nucleus accumbens had similar basal levels of DOPA. Both apomorphine and quinpirole produced a decrease in the dopamine synthesis rate in all brain regions examined. In general, the dopamine D(2)/D(3) receptor agonist quinpirole produced a significantly greater decrease in DOPA accumulation than the dopamine D(1)/D(2) receptor agonist apomorphine. Within the nucleus accumbens, we found no core-shell differences in the agonist-induced suppression of dopamine synthesis, but the rostral pole was less sensitive to the highest dose of both dopamine agonists. These results suggest that differences in dopamine function between the core and shell might not involve region-specific differences in the receptor-mediated autoregulation of dopamine neurotransmission. Moreover, the blunted effect of dopamine agonists in the rostral pole illustrates that this region of the accumbens is functionally distinct, possibly due to a lower dopamine receptor reserve when

  17. Urocortin 2 increases c-Fos expression in serotonergic neurons projecting to the ventricular/periventricular system

    PubMed Central

    Hale, Matthew W.; Stamper, Christopher E.; Staub, Daniel R.; Lowry, Christopher A.

    2010-01-01

    Serotonin plays an important role in the regulation of anxiety states and physiological responses to aversive stimuli. Intracerebroventricular (i.c.v.) injection of the stress- and anxiety-related neuropeptide urocortin 2 (Ucn 2) increases c-Fos expression in serotonergic neurons in the dorsal (DRD) and caudal (DRC) parts of the dorsal raphe nucleus. These regions contain a subset of serotonergic neurons that projects via the dorsal raphe periventricular tract to periventricular structures, including the subfornical organ and ependymal layer, and to the ventricular system. To determine if Ucn 2 activates ventricle/periventricular-projecting serotonergic neurons in the midbrain raphe complex we made i.c.v. injections of the retrograde tracer Fluoro-Gold into the lateral ventricle, followed 7 days later by i.c.v. injection of Ucn 2. The DRD at −8.18 mm and the DRC at −8.54 mm and −9.16 mm bregma were analyzed using a combined brightfield and immunofluorescence technique. Approximately 40% of the ventricle/periventricular-projecting neurons in the subdivisions sampled were serotonergic. Urocortin 2 increased c-Fos expression in ventricle/periventricular-projecting serotonergic neurons in the DRC and in non-ventricle/periventricular-projecting serotonergic neurons in the DRD and DRC. Of the total population of ventricle/periventricular-projecting serotonergic neurons in the DRC at −8.54 and −9.16 mm bregma, 35% expressed c-Fos following Ucn 2 injections. These data are consistent with previous studies showing that i.c.v. injection of Ucn 2 activates subpopulations of serotonergic neurons restricted to the mid-rostrocaudal DRD and DRC, and further demonstrate that these include both subsets of serotonergic neurons that do and do not project to the ventricle/periventricular system. PMID:20382145

  18. Genetic inactivation of glutamate neurons in the rat sublaterodorsal tegmental nucleus recapitulates REM sleep behaviour disorder.

    PubMed

    Valencia Garcia, Sara; Libourel, Paul-Antoine; Lazarus, Michael; Grassi, Daniela; Luppi, Pierre-Hervé; Fort, Patrice

    2017-02-01

    SEE SCHENCK AND MAHOWALD DOI101093/AWW329 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Idiopathic REM sleep behaviour disorder is characterized by the enactment of violent dreams during paradoxical (REM) sleep in the absence of normal muscle atonia. Accumulating clinical and experimental data suggest that REM sleep behaviour disorder might be due to the neurodegeneration of glutamate neurons involved in paradoxical sleep and located within the pontine sublaterodorsal tegmental nucleus. The purpose of the present work was thus to functionally determine first, the role of glutamate sublaterodorsal tegmental nucleus neurons in paradoxical sleep and second, whether their genetic inactivation is sufficient for recapitulating REM sleep behaviour disorder in rats. For this goal, we first injected two retrograde tracers in the intralaminar thalamus and ventral medulla to disentangle neuronal circuits in which sublaterodorsal tegmental nucleus is involved; second we infused bilaterally in sublaterodorsal tegmental nucleus adeno-associated viruses carrying short hairpin RNAs targeting Slc17a6 mRNA [which encodes vesicular glutamate transporter 2 (vGluT2)] to chronically impair glutamate synaptic transmission in sublaterodorsal tegmental nucleus neurons. At the neuroanatomical level, sublaterodorsal tegmental nucleus neurons specifically activated during paradoxical sleep hypersomnia send descending efferents to glycine/GABA neurons within the ventral medulla, but not ascending projections to the intralaminar thalamus. These data suggest a crucial role of sublaterodorsal tegmental nucleus neurons rather in muscle atonia than in paradoxical sleep generation. In line with this hypothesis, 30 days after adeno-associated virus injections into sublaterodorsal tegmental nucleus rats display a decrease of 30% of paradoxical sleep daily quantities, and a significant increase of muscle tone during paradoxical sleep concomitant to a tremendous increase of abnormal motor dream

  19. Cytoarchitectural impairments in the medium spiny neurons of the Nucleus Accumbens core of hyperactive juvenile rats.

    PubMed

    González-Burgos, I; García-Martínez, S; Velázquez-Zamora, D A; Ponce-Rolón, R

    2010-10-01

    Dopaminergic activity in the Nucleus Accumbens has been strongly implicated in the motor hyperactivity associated with Attention deficit hyperactivity disorder. Dopaminergic and glutamatergic terminals converge on the dendritic spines of medium spiny neurons of the nucleus accumbens core, which modulate the excitatory glutamatergic activity. In this work, a Golgi study was carried out to investigate the effects of dopamine depletion on the cytoarchitecture of dendritic spines of nucleus accumbens core medium spiny neurons. The dopaminergic system of newborn male rats was lesioned intracisternally by using 6-hydroxydopamine, and subsequently, the motor activity, spine density, and the proportion of thin, stubby, mushroom, wide, branched, and double spines was compared to those in control and intact animals. Motor activity was significantly increased in the dopamine-depleted animals and while the spine density was reduced, there was no change in the proportion of the specific types of spines. Larger thin spines were observed in the dopamine-depleted animals. Indeed, dopamine depletion may lead to spine retraction due to the disregulation of spine development, and/or an increase in glutamatergic activity. The enlargement of thin spines may suggest a compensatory mechanism to increase the efficiency of synaptic inputs in response to a decrease in spines number. Together, the present findings suggest an alteration to the excitatory/inhibitory balance on dendritic spines of medium spiny neurons of the nucleus accumbens core in hyperactive juvenile rats following early dopamine depletion.

  20. Heterogeneity of firing properties among rat thalamic reticular nucleus neurons

    PubMed Central

    Lee, Sang-Hun; Govindaiah, G; Cox, Charles L

    2007-01-01

    The thalamic reticular nucleus (TRN) provides inhibitory innervation to most thalamic relay nuclei and receives excitatory innervation from both cortical and thalamic neurons. Ultimately, information transfer through the thalamus to the neocortex is strongly influenced by TRN. In addition, the reciprocal synaptic connectivity between TRN with associated thalamic relay nuclei is critical in generating intrathalamic rhythmic activities that occur during certain arousal states and pathophysiological conditions. Despite evidence suggesting morphological heterogeneity amongst TRN neurons, the heterogeneity of intrinsic properties of TRN neurons has not been systematically examined. One key characteristic of virtually all thalamic neurons is the ability to produce action potentials in two distinct modes: burst and tonic. In this study, we have examined the prevalence of burst discharge within TRN neurons. Our intracellular recordings revealed that TRN neurons can be differentiated by their action potential discharge modes. The majority of neurons in the dorsal TRN (56%) lack burst discharge, and the remaining neurons (35%) show an atypical burst that consists of an initial action potential followed by small amplitude, long duration depolarizations. In contrast, most neurons in ventral TRN (82%) display a stereotypical burst discharge consisting of a transient, high frequency discharge of multiple action potentials. TRN neurons that lack burst discharge typically did not produce low threshold calcium spikes or produced a significantly reduced transient depolarization. Our findings clearly indicate that TRN neurons can be differentiated by differences in their spike discharge properties and these subtypes are not uniformly distributed within TRN. The functional consequences of such intrinsic differences may play an important role in modality-specific thalamocortical information transfer as well as overall circuit level activities. PMID:17463035

  1. Local cholinergic and non-cholinergic neural pathways to the rat supraoptic nucleus

    SciTech Connect

    Meeker, M.L.

    1986-01-01

    An estimated two thirds of the input to the supraoptic nucleus of the rat hypothalamus (SON) including a functionally significant cholinergic innervation, arise from local sources of unknown origin. The sources of these inputs were identified utilizing Golgi-Cox, retrograde tracing, choline acetyltransferase immunocytochemistry and anterograde tracing methodologies. Multipolar Golgi impregnated neurons located dorsal and lateral to the SON extend spiney processes into the nucleus. Injections of the retrograde tracers, wheat germ agglutinin or wheat germ agglutinin-horseradish peroxidase, into the SON labeled cells bilaterally in the arcuate nucleus, and ipsilaterally in the lateral hypothalamus, anterior hypothalamus, nucleus of the diagonal band, subfornical organ, medial preoptic area, lateral preoptic area and in the region dorsolateral to the nucleus. Immunocytochemistry for choline acetyltransferase revealed cells within the ventro-caudal portion of cholinergic cell group, Ch4, which cluster dorsolateral to the SON, and extend axon- and dendrite-like processes into the SON. Cells double-labeled by choline acetyltransferase immunocytochemistry and retrograde tracer injections into the SON are localized within the same cholinergic cell group dorsolateral to the SON. Injections of the anterograde tracer, Phaseolus vulgaris-leucoagglutinin, deposited dorsolateral to the SON results in labeled pre-and post-synaptic processes within the SON. The identification and characterization of endogenous immunoglobulin within the SON and other neurons innervating areas lacking a blood-brain barrier established a novel and potentially important system for direct communication of the supraoptic cells with blood-borne constitutents.

  2. Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens

    PubMed Central

    Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C

    2016-01-01

    Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255

  3. Characterization of Ca(2+) channels in rat subthalamic nucleus neurons.

    PubMed

    Song, W J; Baba, Y; Otsuka, T; Murakami, F

    2000-11-01

    The subthalamic nucleus (STN) plays a key role in motor control. Although previous studies have suggested that Ca(2+) conductances may be involved in regulating the activity of STN neurons, Ca(2+) channels in this region have not yet been characterized. We have therefore investigated the subtypes and functional characteristics of Ca(2+) conductances in STN neurons, in both acutely isolated and slice preparations. Acutely isolated STN cells were identified by retrograde filling with the fluorescent dye, Fluoro-Gold. In acutely isolated STN neurons, Cd(2+)-sensitive, depolarization-activated Ba(2+) currents were observed in all cells studied. The current-voltage relationship and current kinetics were characteristic of high-voltage-activated Ca(2+) channels. The steady-state voltage-dependent activation curves and inactivation curves could both be fitted with a single Boltzmann function. Currents evoked with a prolonged pulse, however, inactivated with multiple time constants, suggesting either the presence of more than one Ca(2+) channel subtype or multiple inactivation processes with a single channel type in STN neurons. Experiments using organic Ca(2+) channel blockers revealed that on average, 21% of the current was nifedipine sensitive, 52% was sensitive to omega-conotoxin GVIA, 16% was blocked by a high concentration of omega-agatoxin IVA (200 nM), and the remainder of the current (9%) was resistant to the co-application of all blockers. These currents had similar voltage dependencies, but the nifedipine-sensitive current and the resistant current activated at slightly lower voltages. omega-Agatoxin IVA at 20 nM was ineffective in blocking the current. Together, the above results suggest that acutely isolated STN neurons have all subtypes of high-voltage-activated Ca(2+) channels except for P-type, but have no low-voltage-activated channels. Although acutely isolated neurons provide a good preparation for whole cell voltage-clamp study, dendritic processes are

  4. Hypothalamic paraventricular nucleus stimulation reduces intestinal injury in rats with ulcerative colitis

    PubMed Central

    Deng, Quan-Jun; Deng, Ding-Jing; Che, Jin; Zhao, Hai-Rong; Yu, Jun-Jie; Lu, Yong-Yu

    2016-01-01

    AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis (UC). METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus (PVN), and the effect of the nucleus tractus solitarius (NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the PVN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin (IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the PVN in rats were detected by Western blot. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulation of the PVN on rats with UC were eliminated after chemical damage to the PVN. After glutamate receptor antagonist kynurenic acid was injected into the PVN, the protective effects of the chemical stimulation of the PVN were eliminated in rats with UC. After AVP-Vl receptor antagonist ([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of PVN on UC was also eliminated. After chemical stimulation of the PVN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic PVN provides a protective effect against UC injury in

  5. Glucocorticoid rhythms control the rhythm of expression of the clock protein, Period2, in oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats.

    PubMed

    Segall, L A; Perrin, J S; Walker, C-D; Stewart, J; Amir, S

    2006-07-07

    We investigated the involvement of the adrenal glucocorticoid, corticosterone, in the control of the rhythmic expression of the circadian clock protein, Period2, in forebrain nuclei known to be sensitive to glucocorticoids, stressors and drugs of abuse, the oval nucleus of the bed nucleus of the stria terminalis and the central nucleus of the amygdala. We found previously that the daily rhythm of Period2 in these nuclei is uniquely dependent on the integrity of the adrenal glands (Amir S, Lamont EW, Robinson B, Stewart J (2004) A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis. J Neurosci 24:781-790; Lamont EW, Robinson B, Stewart J, Amir S (2005) The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2. Proc Natl Acad Sci U S A 102:4180-4184). We now show that, in rats, in the absence of the adrenals, corticosterone replacement via the drinking water, which is associated with daily fluctuations in corticosterone levels, restores the rhythm of Period2 in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala. Corticosterone replacement via constant-release pellets has no effect. These results underscore the importance of circadian glucocorticoid signaling in Period2 rhythms in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala and suggest a novel mechanism whereby stressors, drugs of abuse, and other abnormal states that affect the patterns of circulating glucocorticoids can alter the functional output of these nuclei.

  6. Peripheral injection of ghrelin induces Fos expression in the dorsomedial hypothalamic nucleus in rats

    PubMed Central

    Kobelt, Peter; Wisser, Anna-Sophia; Stengel, Andreas; Goebel, Miriam; Inhoff, Tobias; Noetzel, Steffen; Veh, Rüdiger W.; Bannert, Norbert; van der Voort, Ivo; Wiedenmann, Bertram; Klapp, Burghard F.; Taché, Yvette; Mönnikes, Hubert

    2009-01-01

    Peripheral ghrelin has been shown to act as a gut–brain peptide exerting a potent orexigenic effect on food intake. The dorsomedial nucleus of the hypothalamus (DMH) is innervated by projections from other brain areas being part of the network of nuclei controlling energy homeostasis, among others NPY/AgRP-positive fibers arising from the arcuate nucleus (ARC). The aim of the study was to determine if peripherally administered ghrelin affects neuronal activity in the DMH, as assessed by Fos expression. The number of Fos positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), ARC, ventromedial hypothalamic nucleus (VMH), nucleus of the solitary tract (NTS) and in the area postrema(AP) in non-fasted Sprague–Dawley rats in response to intraperitoneally (ip) injected ghrelin (3 nmol/rat) or vehicle (0.15 M NaCl). Peripheral ghrelin induced a significant increase in the number of Fos-ir positive neurons/section compared with vehicle in the ARC (mean±SEM: 49±2 vs. 23±2 neurons/section, p=0.001), PVN (69±5 vs. 34±3, p=0.001), and DMH (142±5 vs. 83±5, p<0.001). Fos-ir positive neurons were mainly localized within the ventral part of the DMH. No change in Fos expression was observed in the VMH (53±8 vs. 48±6, p=0.581), NTS (42±2 vs.40±3, p=0.603), and in the AP (7±1 vs. 5±1, p=0.096). Additional double-labelling with anti-Fos and anti-AgRP revealed that Fos positive neurons in the DMH were encircled by a network of AgRP-ir positive fibers. These data indicate that peripheral ghrelin activates DMH neurons and that NPY-/AgRP-positive fibers may be involved in the response. PMID:18329635

  7. ΔFosB in the supraoptic nucleus contributes to hyponatremia in rats with cirrhosis.

    PubMed

    Cunningham, J Thomas; Nedungadi, Thekkethil Prashant; Walch, Joseph D; Nestler, Eric J; Gottlieb, Helmut B

    2012-07-15

    Bile duct ligation (BDL), a model of hepatic cirrhosis, is associated with dilutional hyponatremia and inappropriate vasopressin release. ΔFosB staining was significantly increased in vasopressin and oxytocin magnocellular neurosecretory cells in the supraoptic nucleus (SON) of BDL rats. We tested the role of SON ΔFosB in fluid retention following BDL by injecting the SON (n = 10) with 400 nl of an adeno-associated virus (AAV) vector expressing ΔJunD (a dominant negative construct for ΔFosB) plus green fluorescent protein (GFP) (AAV-GFP-ΔJunD). Controls were either noninjected or injected with an AAV vector expressing only GFP. Three weeks after BDL or sham ligation surgery, rats were individually housed in metabolism cages for 1 wk. Average daily water intake was significantly elevated in all BDL rats compared with sham ligated controls. Average daily urine output was significantly greater in AAV-GFP-ΔJunD-treated BDL rats compared with all other groups. Daily average urine sodium concentration was significantly lower in AAV-GFP-ΔJunD-treated BDL rats than the other groups, although average daily sodium excretion was not different among the groups. SON expression of ΔJunD produced a diuresis in BDL rats that may be related to decreased circulating levels of vasopressin or oxytocin. These findings support the view that ΔFosB expression in SON magnocellular secretory cells contribute to dilutional hyponatremia in BDL rats.

  8. The effects of bilateral lesions to the dorsal tegmental nucleus on spatial learning in rats.

    PubMed

    Dwyer, Jessica A; Ingram, Matthew L; Snow, Anna C; Thorpe, Christina M; Martin, Gerard M; Skinner, Darlene M

    2013-12-01

    The head-direction (HD) signal is believed to originate in the dorsal tegmental nucleus (DTN) and lesions to this structure have been shown to disrupt HD cell firing in other areas along the HD cell circuit. To investigate the role of the DTN in spatial navigation, rats with bilateral, electrolytic (Experiment 1), or neurotoxic (Experiment 2) lesions to the DTN were compared with sham controls on two tasks that differed in difficulty and could be solved using directional heading. Rats were first trained on a direction problem in a water T maze where they learned to travel either east or west from two locations in the experimental room. DTN-lesioned rats were impaired relative to sham controls, both early in training, on the first block of eight trials, and on the total trials taken to reach criterion. In the food-foraging task, rats were trained to leave a home cage at the periphery of a circular table, find food in the center of the table and return to the home cage. Again, DTN-lesioned rats were impaired relative to sham rats, making more errors on the return component of the foraging trip. These data extend previous cell-recording studies and behavioral tests in which rats with electrolytic DTN lesions were used, and they demonstrate the importance of the direction system to spatial learning.

  9. Angiogenesis induced by prenatal ischemia predisposes to periventricular hemorrhage during postnatal mechanical ventilation

    PubMed Central

    Tosun, Cigdem; Hong, Caron; Carusillo, Brianna; Ivanova, Svetlana; Gerzanich, Volodymyr; Simard, J. Marc

    2014-01-01

    BACKGROUND Three risk factors are associated with hemorrhagic forms of encephalopathy of prematurity (EP): (i) prematurity, (ii) in utero ischemia (IUI) or perinatal ischemia, and (iii) mechanical ventilation. We hypothesized that IUI would induce an angiogenic response marked by activation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), the latter degrading vascular basement membrane and increasing vulnerability to raised intravenous pressure during positive pressure mechanical ventilation. METHODS We studied a rat model of hemorrhagic-EP characterized by periventricular hemorrhages in which a 20-min episode of IUI is induced at E19, pups are born naturally at E21–22, and on P0, are subjected to a 20-min episode of positive pressure mechanical ventilation. Tissues were studied by H&E staining, immunolabeling, immunoblot and zymography. RESULTS Mechanical ventilation of rat pups 2–3 days after 20-min IUI caused widespread hemorrhages in periventricular tissues. IUI resulted in upregulation of VEGF and MMP-9. Zymography confirmed significantly elevated gelatinase activity. MMP-9 activation was accompanied by severe loss of MMP-9 substrates, collagen IV and laminin, in microvessels in periventricular areas. CONCLUSION Our findings are consistent with the hypothesis that positive pressure mechanical ventilation of the newborn in the context of recent prenatal ischemia/hypoxia can predispose to periventricular hemorrhages. PMID:25665055

  10. Does the median preoptic nucleus contribute to sympathetic hyperactivity in spontaneously hypertensive rats?

    PubMed

    Mourão, Aline A; Moreira, Marina C S; Melo, Aryanne B S; Lopes, Paulo R; Rebelo, Ana C S; Rosa, Daniel A; Freiria-Oliveira, André H; Colombari, Eduardo; Pedrino, Gustavo R

    2016-02-01

    The present study sought to determine the involvement of median preoptic nucleus (MnPO) in the regulation of the cardiovascular function and renal sympathetic activity in normotensive (NT) and spontaneously hypertensive rats (SHR). MnPO inhibition evoked by Muscimol (4mM) nanoinjections, elicited fall in MAP and renal sympathoinhibition in NT-rats. Surprisingly, in SHRs these responses were greater than in NT-rats. These results demonstrated, for the first time that MnPO was involved in the tonic control of sympathetic activity in NT and SHRs. Furthermore, our data suggest the MnPO involvement in the increased sympathetic outflow and consequent arterial hypertension observed in SHRs.

  11. Expression and role of TTF-1 in the rat suprachiasmatic nucleus.

    PubMed

    Son, Young June; Yun, Chang Ho; Kim, Jae Geun; Park, Jeong Woo; Kim, Jong Hyun; Kang, Sung Goo; Lee, Byung Ju

    2009-03-13

    We have previously reported that TTF-1, a homeodomain-containing transcription factor, regulates circadian rhythm of pituitary adenylate cyclase-activating polypeptide gene expression in the rat hypothalamus. In this study we found that TTF-1 mRNA was specifically expressed in the rat suprachiasmatic nucleus (SCN) and colocalized with Period 2 (Per2), a circadian feedback loop controller. Interaction between TTF-1 and Per1 and Per2 was demonstrated by immunoprecipitation and immunoblot assays. Moreover, TTF-1 and Per proteins additively stimulated a transcriptional activity of angiotensinogen (AoGen) gene. TTF-1 also activated in vitro rhythm of AoGen transcription determined by secretary alkaline phosphatase (SEAP) reporter system in the NIH3T3 cells. These results suggest that TTF-1 plays a role in the circadian rhythm regulation of the AoGen gene expression via interacting with Per proteins in the rat SCN.

  12. An In Vivo Model of Reduced Nucleus Pulposus Glycosaminoglycan Content in the Rat Lumbar Intervertebral Disc

    PubMed Central

    Boxberger, John I.; Auerbach, Joshua D.; Sen, Sounok; Elliott, Dawn M.

    2009-01-01

    Study Design An in vivo model resembling early stage disc degeneration in the rat lumbar spine. Objective Simulate the reduced glycosaminoglycan content and altered mechanics observed in intervertebral disc degeneration using a controlled injection of chondroitinase ABC (ChABC). Summary of Background Data Nucleus glycosaminoglycan reduction occurs early during disc degeneration; however, mechanisms through which degeneration progresses from this state are unknown. Animal models simulating this condition are essential for understanding disease progression and for development of therapies aimed at early intervention. Methods ChABC was injected into the nucleus pulposus, and discs were evaluated via micro-CT, mechanical testing, biochemical assays, and histology 4 and 12 weeks after injection. Results At 4 weeks, reductions in nucleus glycosaminoglycan level by 43%, average height by 12%, neutral zone modulus by 40%, and increases in range of motion by 40%, and creep strain by 25% were found. Neutral zone modulus and range of motion were correlated with nucleus glycosaminoglycan. At 12 weeks, recovery of some mechanical function was detected as range of motion and creep returned to control levels; however, this was not attributed to glycosaminoglycan restoration, because mechanics were no longer correlated with glycosaminoglycan. Conclusion An in vivo model simulating physiologic levels of glycosaminoglycan loss was created to aid in understanding the relationships between altered biochemistry, altered mechanics, and altered cellular function in degeneration. PMID:18197098

  13. 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.

  14. Effect of barodenervation on cardiovascular responses elicited from the hypothalamic arcuate nucleus of the rat.

    PubMed

    Kawabe, Tetsuya; Kawabe, Kazumi; Sapru, Hreday N

    2012-01-01

    We have previously reported that chemical stimulation of the hypothalamic arcuate nucleus (ARCN) in the rat elicited increases as well as decreases in blood pressure (BP) and sympathetic nerve activity (SNA). The type of response elicited from the ARCN (i.e., increase or decrease in BP and SNA) depended on the level of baroreceptor activity which, in turn, was determined by baseline BP in rats with intact baroreceptors. Based on this information, it was hypothesized that baroreceptor unloading may play a role in the type of response elicited from the ARCN. Therefore, the effect of barodenervation on the ARCN-induced cardiovascular and sympathetic responses and the neurotransmitters in the hypothalamic paraventricular nucleus (PVN) mediating the excitatory responses elicited from the ARCN were investigated in urethane-anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN with microinjections of N-methyl-D-aspartic acid to increases in MAP and GSNA and exaggerated the increases in heart rate (HR). Combined microinjections of NBQX and D-AP7 (ionotropic glutamate receptor antagonists) into the PVN in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated increases in HR. Microinjections of SHU9119 (a melanocortin 3/4 receptor antagonist) into the PVN in barodenervated rats attenuated increases in MAP, GSNA and HR elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). It was concluded that increases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha-MSH and/or ACTH and glutamate from the ARCN neurons projecting

  15. Deep brain stimulation of the pedunculopontine tegmental nucleus modulates neuronal hyperactivity and enhanced beta oscillatory activity of the subthalamic nucleus in the rat 6-hydroxydopamine model.

    PubMed

    Alam, Mesbah; Heissler, Hans E; Schwabe, Kerstin; Krauss, Joachim K

    2012-01-01

    Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) area has been introduced as a novel surgical therapy for dopamine refractory gait problems, freezing and postural instability in the late stage of Parkinson's disease (PD). Lesions of the pedunculopontine tegmental (PPTg) nucleus, the equivalent of the PPN in rodents, were shown to reduce the elevated discharge rate of the subthalamic nucleus (STN) in the 6-hydroxydopamine (6-OHDA) rat model of PD. In order to further elucidate the modulatory effect of the PPTg on the STN we examined the effect of 25 Hz low frequency PPTg stimulation on neuronal single unit activity and oscillatory local field potentials (LFPs) of the STN, and on the electrocorticogram (ECoG) of the primary motor cortex region in rats with unilateral 6-OHDA induced nigrostriatal lesions. Stimulation of the PPTg reduced the enhanced firing rate in the STN, without affecting the firing pattern or approximate entropy (ApEn). It also reduced the activity in the beta band (15-30 Hz) of the STN, which is elevated in 6-OHDA lesioned rats, without affecting beta activity in the motor cortex. We showed a modulatory effect of PPTg stimulation on altered neuronal STN activity in the PD 6-OHDA rat model, indicating that PPTg DBS may alter activity of the basal ganglia circuitry at least partially. It remains unclear, however, how these changes are exactly mediated and whether they are relevant with regard to the descending PPTg projections in the lower brainstem.

  16. Genetic and Dietary Effects on Dendrites in the Rat Hypothalamic Ventromedial Nucleus

    PubMed Central

    LaBelle, Denise R.; Cox, Julia M.; Dunn-Meynell, Ambrose A.; Levin, Barry E.; Flanagan-Cato, Loretta M.

    2009-01-01

    Both genetic and environmental factors contribute to individual differences in body weight regulation. The present study examined a possible role for the dendritic arbor of hypothalamic ventromedial nucleus (VMH) neurons in a model of diet-induced obesity (DIO) in male rats. Rats were screened and selectively bred for being either susceptible, i.e., exhibiting DIO, or diet resistant (DR) when exposed to a 31% fat diet. A 2×2 experimental design was used, based on these two strains of rats and exposure to rat chow versus the 31% fat diet for seven weeks. Golgi-impregnated neurons were measured for soma size and dendrite parameters, including number, length, and direction. As previously observed, each VMH neuron had a single long primary dendrite. Genetic background and diet did not affect soma size or the number of dendrites of VMH neurons. However, genetic background exerted a main effect on the length of the long primary dendrites. In particular, the long primary dendrites were approximately 12.5% shorter on the VMH neurons in the DIO rats compared with DR rats regardless of diet. This effect was isolated to the long primary dendrites extending in the dorsolateral direction, with these long primary dendrites 19% shorter for the DIO group compared with the DR group. This finding implicates the connectivity of the long primary dendrites on VMH neurons in the control of energy balance. The functional significance of these shortened dendrites and their afferents warrants further study. PMID:19698729

  17. Attenuated dopaminergic tone in the paraventricular nucleus contributing to sympathoexcitation in rats with Type 2 diabetes

    PubMed Central

    Liu, Xuefei; Li, Yulong; Mishra, Paras K.; Patel, Kaushik P.

    2013-01-01

    The study was conducted to investigate the role for dopamine in the centrally mediated sympathoexcitatory response in rats with Type 2 diabetes (T2D). T2D was induced by a combination of high-fat diet (HFD) and low-dose streptozotocin (STZ). HFD/STZ treatment for 12–14 wk resulted in significant increase in the number of FosB-positive cells in the paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM). In anesthetized rats, administration of exogenous dopamine (dopamine hydrochloride, 20 mM) in the PVN, but not in the RVLM, elicited decreases in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in control rats and but not in the T2D rats. Blocking the endogenous dopamine with dopamine D1/D5 receptor antagonist SCH39166 (2 mM) in the PVN and RVLM, resulted in increases in RSNA, MAP, and heart rate (HR) in both control and T2D rats. These responses were significantly attenuated in T2D rats compared with control rats (PVN − ΔRSNA: 21 ± 10 vs. 44 ± 2%; ΔMAP: 7 ± 3 vs. 19 ± 6 mmHg, ΔHR: 17 ± 5 vs. 32 ± 4 bpm, P < 0.05). There were no significant increases in response to dopamine D2/D3 receptor antagonist raclopride application in the PVN and RVLM of both control and T2D rats. Furthermore, there were decreased dopamine D1 receptor and D2 receptor expressions in the PVN of T2D rats. Taken together, these data suggest that reduced endogenous dopaminergic tone within the PVN may contribute to the sympathoexcitation in T2D. PMID:24305061

  18. Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour

    PubMed Central

    Roberts, Michael D; Toedebusch, Ryan G; Wells, Kevin D; Company, Joseph M; Brown, Jacob D; Cruthirds, Clayton L; Heese, Alexander J; Zhu, Conan; Rottinghaus, George E; Childs, Thomas E; Booth, Frank W

    2014-01-01

    We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVRnon-run and HVRnon-run), as well as in rats after 6 days of voluntary wheel running (LVRrun and HVRrun). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that ‘cell cycle’-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9–10 LVRnon-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive) neurons (P < 0.001) than their G9–10 HVR counterparts. However, voluntary running wheel access in our G9–10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. PMID:24665095

  19. Dietary sodium deprivation reduces gustatory neural responses of the parabrachial nucleus in rats.

    PubMed

    Huang, Tao; Yan, Jianqun

    2008-02-27

    Acute sodium depletion induced by furosemide reduces gustatory responses of parabrachial nucleus (PBN) neurons to 0.3-0.5M NaCl in rats. However, in the rat nucleus of the solitary tract (NST), where taste-responsive cells project to the PBN, acute sodium depletion and dietary sodium deprivation elicit different response profiles to lingual NaCl stimulation. To examine the effect of dietary sodium deprivation on the responses of PBN gustatory neurons, we observed the taste responses of the PBN neurons to the four taste qualities and serial concentrations of NaCl in 15-day dietary sodium-deprived and control rats. The results showed that sodium deprivation reduced the responses of PBN taste neurons to 0.1-1.0M NaCl, but not to other tastants. Based on the analyses classified by best-stimulus categories, the number of NaCl-best neurons decreased from 68% to 45% following dietary sodium deprivation, and the responses of the NaCl-best neurons to 0.03-1.0M NaCl were significantly inhibited. Multidimensional scaling illustrated that sodium deprivation increased the similarity of the response profiles of the NaCl-best neurons. These findings suggest that dietary sodium deprivation might modulate sodium intake via increasing aversive threshold for salt rather enhancing salt discrimination.

  20. Oxytocin in Brattleboro rats: increased synthesis is contrasted by blunted intrahypothalamic release from supraoptic nucleus neurones.

    PubMed

    Zelena, D; Pintér, O; Langnaese, K; Richter, K; Landgraf, R; Makara, G B; Engelmann, M

    2013-08-01

    Adult male Brattleboro rats were used to investigate the impact of the congenital absence of vasopressin on the release pattern of oxytocin (OXT) within the hypothalamic supraoptic nucleus (SON) in response to a 10-min forced swimming session and osmotic stimulation. Both immunohistochemical and in situ hybridisation data suggest that vasopressin-deficient animals have more oxytocin-synthesising neurones in the SON than homozygous wild-type controls. Unexpectedly, both forced swimming and peripheral osmotic stimulation resulted in a blunted release profile of oxytocin within the SON of vasopressin-deficient rats compared to controls. A similar intranuclear OXT response to direct osmotic stimulation of the SON by retrodialysis with hypertonic Ringer's solution in both genotypes confirmed the capability of SON neurones to locally release oxytocin in vasopressin-deficient rats, indicating an altered processing of information originating from multisynaptic inputs rather than a deficit in release capacity. Taken together with data obtained in previous studies, the present findings provide evidence suggesting that autocrine and paracrine signalling of magnocellular neurones differs within the paraventricular nucleus and the SON. Thus, significant alterations in intra-SON oxytocin mRNA levels cannot easily be extrapolated to intranuclear release profiles and the local signal intensity of this neuropeptide after physiological stimulation.

  1. Hypothalamic paraventricular nucleus differentially supports lumbar and renal sympathetic outflow in water-deprived rats.

    PubMed

    Stocker, Sean D; Hunwick, Kimberly J; Toney, Glenn M

    2005-02-15

    The present study sought to determine whether the hypothalamic paraventricular nucleus (PVN) contributes in a time-dependent manner to the differential patterning of lumbar and renal sympathetic nerve activity (SNA) in water-deprived rats. Mean arterial blood pressure (MAP) and both lumbar SNA (LSNA) and renal SNA (RSNA) were recorded simultaneously in control, 24 and 48 h water-deprived rats, and the PVN was inhibited bilaterally with microinjection of the GABA(A) agonist muscimol (100 pmol in 100 nl per side). Inhibition of the PVN significantly decreased RSNA in 48 h water-deprived rats but not in 24 h water-deprived or control rats (48 h, -17 +/- 4%; 24 h, -2 +/- 5%; control, 4 +/- 6%; P < 0.05). In addition, injection of muscimol significantly decreased LSNA in 48 and 24 h water-deprived rats but not in control rats (48 h, -41 +/- 4%; 24 h, -14 +/- 6%; control, -3 +/- 2%; P < 0.05). Interestingly, the decrease in LSNA was significantly greater than the decrease in RSNA of 24 and 48 h water-deprived rats (P < 0.05). Inhibition of the PVN also significantly decreased MAP to a greater extent in 48 and 24 h water-deprived rats compared to control rats (48 h, -34 +/- 5 mmHg; 24 h, -26 +/- 4 mmHg; control, -15 +/- 3 mmHg; P < 0.05). When 48 h water-deprived rats were acutely rehydrated by giving access to tap water 2 h before experiments, inhibition of the PVN with muscimol did not alter LSNA (-12 +/- 8%) or RSNA (7 +/- 4%) but did produce a small decrease in MAP (-15 +/- 4 mmHg) that was not different from control rats. In a parallel set of experiments, acute rehydration of 48 h water-deprived rats significantly attenuated the increased Fos immunoreactivity in PVN neurones that project to the spinal cord or rostral ventrolateral medulla. Collectively, the present findings suggest that PVN autonomic neurones are synaptically influenced during water deprivation, and that these neurones differentially contribute to LSNA and RSNA in water-deprived rats.

  2. Estradiol implants in the arcuate nucleus induce lactogenesis in virgin rats. Role of progesterone.

    PubMed

    Carón, R W; Deis, R P

    1998-01-01

    The aim of this study was to determine the effect of the centrally administered estradiol, and the effects of the consequent hypersecretion of prolactin (PRL) and progesterone, on lactogenesis as evaluated by mammary accumulation of casein and lactose. Bilateral cannulae containing 17beta-estradiol or cholesterol were implanted in the arcuate nucleus of virgin rats on the day of estrus (Day 0). In the first experiment different groups of rats were killed on Days 6, 9, 15, 17, or 19. Trunk blood was collected and abdominal mammary glands were taken. In the second experiment, estradiol-implanted rats received the progesterone antagonist mifepristone or vehicle at 14.00 h on Day 8 or 16 post-implant, and were killed 28 or 48 h later. Serum PRL and progesterone and mammary casein were measured by RIA and lactose was determined by an enzymatic assay. Estradiol-implanted rats showed a significant increase in both milk components at all time points after implant compared to controls. On Day 9 after estradiol implant, mifepristone had no effect on mammary content of casein or lactose. By contrast, on Day 16, mifepristone markedly increased both casein and lactose contents without modifying serum PRL and progesterone concentrations. In conclusion, 17beta-estradiol implants in the arcuate nucleus of virgin rats results in hyperprolactinaemia and stimulates mammary accumulation of casein and lactose in the absence of feto-placental units. Despite the prolonged luteal activation, the sustained high levels of circulating progesterone become inhibitory to lactogenesis after a relatively long period after implant.

  3. Sexual dimorphism in the bed nucleus of the accessory olfactory tract in the rat.

    PubMed

    Collado, P; Guillamón, A; Valencia, A; Segovia, S

    1990-11-01

    This work investigates the existence of sex differences in the volume and number of neurons and glial cells in the bed nucleus of the accessory olfactory tract (BAOT). Males showed larger volume and number of cells than female rats. Early postnatal (day 1 after birth) orchidectomy in males, and androgenization in females, reversed these differences. No sex differences were found in BAOT glial cells. The sexual dimorphism found in the neuron/glial cell ratio reflects sex differences in neuron number. The existence of sexual dimorphism in the BAOT supports our earlier hypothesis which states that the vomeronasal system (VNS) is sexually dimorphic.

  4. The centrally projecting Edinger-Westphal nucleus--I: Efferents in the rat brain.

    PubMed

    Dos Santos Júnior, Edmilson D; Da Silva, André V; Da Silva, Kelly R T; Haemmerle, Carlos A S; Batagello, Daniella S; Da Silva, Joelcimar M; Lima, Leandro B; Da Silva, Renata J; Diniz, Giovanne B; Sita, Luciane V; Elias, Carol F; Bittencourt, Jackson C

    2015-10-01

    The oculomotor accessory nucleus, often referred to as the Edinger-Westphal nucleus [EW], was first identified in the 17th century. Although its most well known function is the control of pupil diameter, some controversy has arisen regarding the exact location of these preganglionic neurons. Currently, the EW is thought to consist of two different parts. The first part [termed the preganglionic EW-EWpg], which controls lens accommodation, choroidal blood flow and pupillary constriction, primarily consists of cholinergic cells that project to the ciliary ganglion. The second part [termed the centrally projecting EW-EWcp], which is involved in non-ocular functions such as feeding behavior, stress responses, addiction and pain, consists of peptidergic neurons that project to the brainstem, the spinal cord and prosencephalic regions. However, in the literature, we found few reports related to either ascending or descending projections from the EWcp that are compatible with its currently described functions. Therefore, the objective of the present study was to systematically investigate the ascending and descending projections of the EW in the rat brain. We injected the anterograde tracer biotinylated dextran amine into the EW or the retrograde tracer cholera toxin subunit B into multiple EW targets as controls. Additionally, we investigated the potential EW-mediated innervation of neuronal populations with known neurochemical signatures, such as melanin-concentrating hormone in the lateral hypothalamic area [LHA] and corticotropin-releasing factor in the central nucleus of the amygdala [CeM]. We observed anterogradely labeled fibers in the LHA, the reuniens thalamic nucleus, the oval part of the bed nucleus of the stria terminalis, the medial part of the central nucleus of the amygdala, and the zona incerta. We confirmed our EW-LHA and EW-CeM connections using retrograde tracers. We also observed moderate EW-mediated innervation of the paraventricular nucleus of the

  5. Effect of intermittent hypoxia on arcuate nucleus in the leptin-deficient rat.

    PubMed

    Ciriello, John; Moreau, Jason M; McCoy, Aaron; Jones, Douglas L

    2016-07-28

    Intermittent hypoxia (IH) is a major pathophysiological consequence of obstructive sleep apnea. Recently, it has been shown that IH results in changes in body energy balance, leptin secretion and concomitant alterations in arcuate nucleus (ARC). In this study, the role of leptin on these changes was investigated in leptin-deficient rats exposed to IH or normoxic control conditions. Body weights, consumatory and locomotor behaviours, and protein signaling in ARC were assessed immediately after IH exposure. Compared to normoxia, IH altered body weight, food intake, locomotor pattern, and the plasma concentration of leptin and angiotensin II in the wild-type rat. However, these changes were not observed in the leptin-deficient rat. Within ARC of wild-type animals, IH increased phosphorylated signal transducer and activator of transcription 3 and pro-opiomelanocortin protein expression, but not in the leptin-deficient rat. The long-form leptin receptor protein expression was not altered following IH in either rat strain. These data suggest that leptin is involved in mediating the alterations to body energy balance and ARC activity following IH. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Ascorbate reduces morphine-induced extracellular DOPAC level in the nucleus accumbens: A microdialysis study in rats.

    PubMed

    Rajaei, Z; Alaei, H; Nasimi, A; Amini, H; Ahmadiani, A

    2005-08-16

    Most drugs of abuse increase dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) release in the shell of the nucleus accumbens. The effects of ascorbate, which is known to modulate dopamine neurotransmission, on the extracellular level of DOPAC in the nucleus accumbens of naive rats and of rats treated acutely with morphine were studied by using in vivo microdialysis and high performance liquid chromatography with electrochemical detection (HPLC-ECD). Acute morphine (20 mg/kg ip) treatment increased the level of DOPAC in the nucleus accumbens to approximately 170% of basal level. Acute treatment with ascorbate (500 mg/kg ip) alone did not alter nucleus accumbens' DOPAC level, but pretreatment with ascorbate (500 mg/kg ip) 30 min before morphine administration attenuated the effects of acute morphine on the level of DOPAC. These results suggest that ascorbate modulates the mesolimbic dopaminergic pathway.

  7. Bilateral periventricular nodular heterotopia with megalencephaly: a case report.

    PubMed

    Abe, Yu; Kobayashi, Satoru; Wakusawa, Keisuke; Tanaka, Soichiro; Inui, Takehiko; Yamamoto, Toshiyuki; Kunishima, Shinji; Haginoya, Kazuhiro

    2014-06-01

    Bilateral periventricular nodular heterotopia is a neuronal migration disorder characterized by gray matter cellular rests in the periventricular regions. Megalencephaly has not been reported in children with bilateral periventricular nodular heterotopia. No other disorder with a similar phenotype has been reported. Here we report the case of a 5-year-old Japanese boy with bilateral periventricular nodular heterotopia and megalencephaly. Relative macrocephaly was evident at birth, and bilateral periventricular nodular heterotopia and megalencephaly were noted on magnetic resonance imaging (MRI). However, no hydrocephalus or indication of cerebral cortical dysplasia was seen. A mild intellectual disability was present, but the patient had no history of seizures. Genetic analysis revealed no mutation on the capillary sequences for FLNA, and no pathogenic abnormalities were evident on array comparative genomic hybridization. This case could represent a new disease entity: bilateral periventricular nodular heterotopia with megalencephaly.

  8. Met-enkephalin induces fast synaptic plasticity of magnocellular neurons in the rat supraoptic nucleus.

    PubMed

    Blanco, E; Carretero, J; Riesco, J M; Sanchez, F; Juanes, J A; Vazquez, R

    1992-01-01

    A morphometric-ultrastructural study was made of the supraoptic nucleus of rats of both sexes following central administration of met-enkephalin. Ten minutes after met-enkephalin treatment the number of axo-somatic synapses was significantly increased. This effect was more pronounced in female rats than in males and could be prevented by preceding administration of naloxone. Animals that received naloxone followed by met-enkephalin showed a dilation of the rough endoplasmic reticulum into a vesicular shape. Our results provide preliminary evidence for a fast remodeling of synaptic input to magnocellular hypothalamic neurons. It is likely that the known inhibitory action of opioids on the hypothalamo-neurohypophysial system is partly mediated by this plasticity.

  9. Fine structural changes in the lateral vestibular nucleus of aging rats

    NASA Technical Reports Server (NTRS)

    Johnson, J. E., Jr.; Miquel, J.

    1974-01-01

    The fine structure of the lateral vestibular nucleus was investigated in Sprague-Dawley rats, that were sacrified at 4 weeks, 6-8 weeks, 6-8 months, and 18-20 months of age. In the neuronal perikaria, the following age-associated changes were seen with increasing frequency with advancing age: rodlike nuclear inclusions and nuclear membrane invaginations; cytoplasmic dense bodies with the characteristics of lipofuscin; and moderate disorganization of the granular endoplasmic reticulum. Dense bodies were also seen in glial cells. Rats 18 to 20 months old showed dendritic swellings, axonal degeneration, and an apparent increase in the number of axosomatic synaptic terminals containing flattened vesicles (presumed to be inhibitory in function).

  10. Amygdala central nucleus lesions attenuate acoustic startle stimulus-evoked heart rate changes in rats.

    PubMed

    Young, B J; Leaton, R N

    1996-04-01

    Amygdala central nucleus (CNA) lesions were used to test the hypothesis that stimulus-evoked heart rate changes can reflect the development of fear during acoustic startle testing. A 120-dB white noise startle stimulus produced freezing as well as phasic heart rate accelerations and decelerations, and an abrupt decrease in tonic heart rate, in sham-operated rats. These responses were all significantly reduced in CNA-lesioned rats. In contrast, an 87-dB stimulus elicited only significant phasic decelerations that were similarly attenuated by the CNA lesions. In a follow-up experiment, the CNA lesions also attenuated phasic cardiac decelerations evoked by a conditioned stimulus-like, 85-dB pure tone. The results support the contention (B. J. Young & R.N. Leaton, 1994) that heart rate changes can reflect fear conditioned during acoustic startle testing and, in addition, suggest that the amygdala mediates responses to nonsignal acoustic stimuli.

  11. Fine structural changes in the lateral vestibular nucleus of aging rats

    NASA Technical Reports Server (NTRS)

    Johnson, J. E., Jr.; Miquel, J.

    1974-01-01

    The fine structure of the lateral vestibular nucleus was investigated in Sprague-Dawley rats, that were sacrified at 4 weeks, 6-8 weeks, 6-8 months, and 18-20 months of age. In the neuronal perikaria, the following age-associated changes were seen with increasing frequency with advancing age: rodlike nuclear inclusions and nuclear membrane invaginations; cytoplasmic dense bodies with the characteristics of lipofuscin; and moderate disorganization of the granular endoplasmic reticulum. Dense bodies were also seen in glial cells. Rats 18 to 20 months old showed dendritic swellings, axonal degeneration, and an apparent increase in the number of axosomatic synaptic terminals containing flattened vesicles (presumed to be inhibitory in function).

  12. Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats.

    PubMed

    Arnold, Amy C; Diz, Debra I

    2014-12-01

    The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 ± 2 wk of age) urethane/chloralose anesthetized Sprague-Dawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 ± 0.19 baseline vs. 0.71 ± 0.15 ms/mmHg after leptin; P = 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 ± 0.13 baseline vs. 1.19 ± 0.26 at 10 min vs. 1.87 ± 0.32 at 60 min vs. 1.22 ± 0.54 ms/mmHg at 120 min; P = 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging. Copyright © 2014 the American Physiological Society.

  13. Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

    PubMed Central

    Arnold, Amy C.

    2014-01-01

    The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 ± 2 wk of age) urethane/chloralose anesthetized Sprague-Dawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 ± 0.19 baseline vs. 0.71 ± 0.15 ms/mmHg after leptin; P = 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 ± 0.13 baseline vs. 1.19 ± 0.26 at 10 min vs. 1.87 ± 0.32 at 60 min vs. 1.22 ± 0.54 ms/mmHg at 120 min; P = 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging. PMID:25260611

  14. Auditory Responses to Electric and Infrared Neural Stimulation of the Rat Cochlear Nucleus

    PubMed Central

    Verma, Rohit; Guex, Amelie A.; Hancock, Kenneth E.; Durakovic, Nedim; McKay, Colette M.; Slama, Michaël C. C.; Brown, M. Christian; Lee, Daniel J.

    2014-01-01

    In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported “optophonic” effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. PMID:24508368

  15. A cluster analysis of the neurons of the rat interpeduncular nucleus.

    PubMed Central

    Gioia, M; Vizzotto, L; Bianchi, R

    1994-01-01

    The morphometric characteristics of the neurons of the interpeduncular nucleus (IPN) in the rat were investigated by cluster analysis in order to identify neuronal groups which are morphometrically homogeneous, and to define their position and density in the IPN subnuclei. Two clusters of cells were detected. Cluster 1 neurons had a larger perikaryal size with a mean cross-sectional area of 170 microns2 and a high nuclear/cytoplasmic ratio. They were located mainly in the pars dorsalis (37%) and pars medialis (34%) rather than in the pars lateralis (29%). Cluster 1 neurons were also more frequent at the rostral (31%) and caudal (57%) poles than in the central part of the IPN. Cluster 2 cells showed a smaller mean perikaryal area (110 microns2), a small nucleus and abundant cytoplasm. They were equally distributed throughout the whole IPN. These findings suggest the existence of a magnocellular region at the rostral pole of the IPN which has not been described previously. The presence of IPN regions endowed with specific cytoarchitectural characteristics is discussed with respect to the complex neurochemical organisation of the nucleus. Images Fig. 1 Fig. 2 Fig. 4 PMID:7649781

  16. Homologous upregulation of sst2 somatostatin receptor expression in the rat arcuate nucleus in vivo.

    PubMed

    Tannenbaum, G S; Turner, J; Guo, F; Videau, C; Epelbaum, J; Beaudet, A

    2001-07-01

    In vitro studies using various cell systems have provided conflicting results regarding homologous regulation of somatostatin (SRIH) receptors, and information on whether SRIH regulates the expression of its own receptors in vivo is lacking. In the present study we examined, by in situ hybridization, the effects of pretreatment with the sst2-preferring SRIH analog, octreotide, in vivo, on mRNA levels of two SRIH receptor subtypes, sst1 and sst2, in rat brain and pituitary. (125)I-[DTrp(8)]-SRIH binding was also measured in these regions. Three hours after the iv injection of 50 microg octreotide to conscious adult male rats, there was a 46% increase (p < 0.01) in the labeling density of sst2 mRNA-expressing cells in the hypothalamic arcuate nucleus compared to normal saline-pretreated controls, but not in any of the other brain regions examined. Computer-assisted image analysis revealed that 3 h exposure to octreotide significantly (p < 0.01) augmented both the number and labeling density of sst2 mRNA-expressing cells in the arcuate nucleus, compared to those in saline-treated controls. By contrast, within the anterior pituitary gland, in vivo exposure to octreotide did not affect the expression of sst2 mRNA. No changes in sst1 mRNA-expressing cells were observed after octreotide treatment in any of the regions measured, indicating that the observed effects were homologous, i.e. specific of the receptor subtype stimulated. Octreotide pretreatment was also without effect on the density of (125)I-[DTrp(8)]-SRIH binding in either the arcuate nucleus or pituitary. These results demonstrate, for the first time, that SRIH preexposure in vivo upregulates the expression of a subtype of its own receptors, sst2, within the central nervous system. They further suggest that pretreatment with SRIH in vivo does not cause sst2 receptor desensitization in arcuate nucleus and pituitary. Such homologous regulatory mechanisms may play an important role in the neuroendocrine control

  17. Neuronal Entropy-Rate Feature of Entopeduncular Nucleus in Rat Model of Parkinson's Disease.

    PubMed

    Darbin, Olivier; Jin, Xingxing; Von Wrangel, Christof; Schwabe, Kerstin; Nambu, Atsushi; Naritoku, Dean K; Krauss, Joachim K; Alam, Mesbah

    2016-03-01

    The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus, i.e. the entopeduncular nucleus (EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In both control subjects and subjects with 6-OHDA lesion of dopamine (DA) the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15 and 25 Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25 Hz. Our data establishes that the nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions such as movement disorders.

  18. Studies on functional connections between the supraoptic nucleus and the stomach in rats.

    PubMed

    Lu, Chang-Liang; Li, Zhao-Ping; Zhu, Jian-Ping; Zhao, Dong-Qin; Ai, Hong-Bin

    2011-05-01

    The present study was to investigate whether there are functional connections between the hypothalamic supraoptic nucleus (SON) and the stomach, which is the case with the paraventricular nucleus. The rats were divided into four groups. Group I: the neuronal discharge was recorded extracellularly in the NTS, DMV or SON before and after cold physiological saline (4°C) was perfused into the stomach and effused from the duodenum. Group II: the rats were stimulated as for Group I and c-Fos expression in NTS, DMV and SON was examined. Group III: the control to Group II. Group IV: gastric motility was recorded continuously before and after microinjection of L: -Glu into the SON. In Group I, the discharge frequency increased in all the three nuclei, while in Group II, Fos expression in NTS, DMV and SON was, respectively, greater than that of Group III. In Group IV, microinjection of L: -Glu (5 nmol) into SON significantly inhibited gastric motility. These data suggest there are functional connections between SON and stomach.

  19. PKC in rat dorsal raphe nucleus plays a key role in sleep-wake regulation.

    PubMed

    Li, Sheng-Jie; Cui, Su-Ying; Zhang, Xue-Qiong; Yu, Bin; Sheng, Zhao-Fu; Huang, Yuan-Li; Cao, Qing; Xu, Ya-Ping; Lin, Zhi-Ge; Yang, Guang; Cui, Xiang-Yu; Zhang, Yong-He

    2015-12-03

    Studies suggest a tight relationship between protein kinase C (PKC) and circadian clock. However, the role of PKC in sleep-wake regulation remains unclear. The present study was conducted to investigate the role of PKC signaling in sleep-wake regulation in the rat. Our results showed that the phosphorylation level of PKC in dorsal raphe nucleus (DRN) was decreased after 6h sleep deprivation, while no alterations were found in ventrolateral preoptic nucleus (VLPO) or locus coeruleus (LC). Microinjection of a pan-PKC inhibitor, chelerythrine chloride (CHEL, 5 or 10nmol), into DRN of freely moving rats promoted non rapid eye movement sleep (NREMS) without influences on rapid eye movement sleep (REMS). Especially, CHEL application at 5nmol increased light sleep (LS) time while CHEL application at 10nmol increased slow wave sleep (SWS) time and percentage. On the other hand, microinjection of CaCl2 into DRN not only increased the phosphorylation level of PKC, but also reduced NREMS time, especially SWS time and percentage. While CHEL abolished the inhibitory effect of CaCl2 on NREMS and SWS. These data provide the first direct evidence that inhibition of intracellular PKC signaling in DRN could increase NREMS time including SWS time and percentage, while activation of PKC could suppress NREMS and reduce SWS time and percentage. These novel findings further our understanding of the basic cellular and molecular mechanisms of sleep-wake regulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Edaravone ameliorates compression-induced damage in rat nucleus pulposus cells.

    PubMed

    Lin, Hui; Ma, Xuan; Wang, Bai-Chuan; Zhao, Lei; Liu, Jian-Xiang; Pu, Fei-Fei; Hu, Yi-Qiang; Hu, Hong-Zhi; Shao, Zeng-Wu

    2017-09-20

    Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells. Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca(2+)]i) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot. Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca(2+)]i. In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells. These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD. Copyright © 2017. Published by Elsevier Inc.

  1. Biperiden hydrochlorate ameliorates dystonia of rats produced by microinjection of sigma ligands into the red nucleus.

    PubMed

    Yoshida, K; Takahashi, H; Sato, K; Higuchi, H; Shimizu, T

    2000-11-01

    It has been reported that the imbalance of anticholinergic and antidopaminergic activity of each neuroleptic drug correlates with the capacity to produce neuroleptic-induced acute dystonia (NAD) and the major focus of NAD is thought to be the striatum. Anticholinergic drugs are highly effective on NAD, but they are partially effective on neuroleptic-induced tardive dystonia and their effect on idiopathic dystonia is disappointing. Recently, it has been reported that the unilateral microinjection of sigma (sigma) ligands into the red nucleus induces torticollis of rats. This animal model appears to be a model of dystonia, but it is not clear whether it is suitable for NAD in man. To clarify this issue, we investigated the effect of an anticholinergic drug, biperiden hydrochlorate (BH), on this animal model. This study revealed that BH dose-dependently ameliorated dystonia of rats induced by two sigma ligands, whether each sigma ligand had dopaminergic affinity or not. This animal model of dystonia appears to be a model of NAD in man from the viewpoint of treatment-response. The results also suggest that not only dopaminergic and cholinergic systems but also sigma system, and not only the striatum but also the red nucleus, may play an important role in the pathophysiology of NAD.

  2. Catalase inhibition in the Arcuate nucleus blocks ethanol effects on the locomotor activity of rats.

    PubMed

    Sanchis-Segura, Carles; Correa, Mercé; Miquel, Marta; Aragon, Carlos M G

    2005-03-07

    Previous studies have demonstrated that there is a bidirectional modulation of ethanol-induced locomotion produced by drugs that regulate brain catalase activity. In the present study we have assessed the effect in rats of intraperitoneal, intraventricular or intracraneal administration of the catalase inhibitor sodium azide in the locomotor changes observed after ethanol (1 g/kg) administration. Our results show that sodium azide prevents the effects of ethanol in rats locomotion not only when sodium azide was systemically administered but also when it was intraventricularly injected, then confirming that the interaction between catalase and ethanol takes place in Central Nervous System (CNS). Even more interestingly, the same results were observed when sodium azide administration was restricted to the hypothalamic Arcuate nucleus (ARC), a brain region which has one of the highest levels of expression of catalase. Therefore, the results of the present study not only confirm a role for brain catalase in the mediation of ethanol-induced locomotor changes in rodents but also point to the ARC as a major neuroanatomical location for this interaction. These results are in agreement with our reports showing that ethanol-induced locomotor changes are clearly dependent of the ARC integrity and, especially of the POMc-synthesising neurons of this nucleus. According to these data we propose a model in which ethanol oxidation via catalase could produce acetaldehyde into the ARC and to promote a release of beta-endorphins that would activate opioid receptors to produce locomotion and other ethanol-induced neurobehavioural changes.

  3. Olanzapine treatment of adolescent rats alters adult reward behaviour and nucleus accumbens function.

    PubMed

    Vinish, Monika; Elnabawi, Ahmed; Milstein, Jean A; Burke, Jesse S; Kallevang, Jonathan K; Turek, Kevin C; Lansink, Carien S; Merchenthaler, Istvan; Bailey, Aileen M; Kolb, Bryan; Cheer, Joseph F; Frost, Douglas O

    2013-08-01

    Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug (APD) treatment. Most APDs are potent antagonists or partial agonists of dopamine (DA) D₂ receptors; atypical APDs also have multiple serotonergic activities. DA and serotonin regulate many neurodevelopmental processes. Thus, early life APD treatment can, potentially, perturb these processes, causing long-term behavioural and neurobiological sequelae. We treated adolescent, male rats with olanzapine (Ola) on post-natal days 28-49, under dosing conditions that approximate those employed therapeutically in humans. As adults, they exhibited enhanced conditioned place preference for amphetamine, as compared to vehicle-treated rats. In the nucleus accumbens core, DA D₁ receptor binding was reduced, D₂ binding was increased and DA release evoked by electrical stimulation of the ventral tegmental area was reduced. Thus, adolescent Ola treatment enduringly alters a key behavioural response to rewarding stimuli and modifies DAergic neurotransmission in the nucleus accumbens. The persistence of these changes suggests that even limited periods of early life Ola treatment may induce enduring changes in other reward-related behaviours and in behavioural and neurobiological responses to therapeutic and illicit psychotropic drugs. These results underscore the importance of improved understanding of the enduring sequelae of paediatric APD treatment as a basis for weighing the benefits and risks of adolescent APD therapy, especially prophylactic treatment in high-risk, asymptomatic patients.

  4. The monosynaptic excitatory connections of single trigeminal interneurones to the V motor nucleus of the rat.

    PubMed Central

    Appenteng, K; Conyers, L; Moore, J A

    1989-01-01

    1. We have used the extracellular spike-triggered averaging method to identify a population of trigeminal interneurones that make monosynaptic connections within the V motor nucleus. The experiments were performed on rats anaesthetized with pentobarbitone (60 mg/kg I.V.; supplementary doses given as necessary to maintain a deep level of anaesthesia). 2. A tungsten microelectrode (tip exposure of some 200 microns) was inserted into the masseter motoneurone pool to allow recording of extracellular activity. A glass electrode filled with DL-homocysteic acid was used to make simultaneous extracellular recordings of the firing of single neurones in the region immediately caudal to the motor nucleus. 3. Fifty-eight out of 166 interneurones tested gave unitary extracellular fields in the motor nucleus. The responses consisted of a terminal spike (presynaptic spike) followed by a negative field of duration approximately 3 ms and amplitude 0.4-10.8 microV. The mean latency between the positive peak of the terminal spike and the onset of the field (synaptic delay) was 0.43 ms (S.D. = 0.10 ms), and the mean latency from the onset of the interneurone spike to the positive peak of the presynaptic spike was 0.35 ms (S.D. = 0.22 ms). Thus the interneurones project directly to the motor nucleus where they then make monosynaptic connections. 4. The negative extracellular fields were taken to reflect an excitatory synaptic input onto neurones within the motor nucleus. The fields were of maximum amplitude at the point of maximum masseter motoneurone antidromic field, suggesting that the connection may be onto elevator motoneurones. 5. The location of the interneurone appeared to the main factor governing the likelihood of obtaining a field. Interneurones located more than 400 microns from the caudal border of the motor nucleus rarely produced fields whereas most of those located within this distance gave fields. This pattern of distribution is strikingly similar to that of trigeminal

  5. Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat.

    PubMed

    Fadda, Paola; Scherma, Maria; Fresu, Alessandra; Collu, Maria; Fratta, Walter

    2003-10-01

    Evidence recently provided has suggested a specific involvement of the GABAergic system in modulating positive reinforcing properties of several drugs of abuse through an action on mesolimbic dopaminergic neurons. The GABA(B) receptor agonist baclofen has been proposed as a potential therapeutic agent for the clinical treatment of several forms of drug addiction. In the present study, using the in vivo microdialysis technique, we investigated the effect of baclofen on nicotine, cocaine, and morphine-induced increase in extracellular dopamine (DA) levels in the shell of the nucleus accumbens, a brain area supposedly involved in the modulation of the central effects of several drugs of abuse, of freely moving rats. As expected, nicotine (0.6 mg/kg s.c.), morphine (5 mg/kg s.c.), and cocaine (7.5 mg/kg i.p.) administration in rats induced a marked increase in extracellular DA concentrations in the nucleus accumbens, reaching a maximum value of +205 +/- 8.4%, +300 +/- 22.2%, and +370 +/- 30.7%, respectively. Pretreatment with baclofen (1.25 and 2.5 mg/kg i.p.) dose-dependently reduced the nicotine-, morphine-, and cocaine-evoked DA release in the shell of the nucleus accumbens. Furthermore, baclofen alone did not elicit changes in basal DA extracellular levels up to 180 min. Taken together, our data are in line with previous reports demonstrating the ability of baclofen to modulate the mesolimbic DAergic transmission and indicate baclofen as a putative candidate in the pharmacotherapy of polydrug abuse.

  6. Peripherally injected CCK-8S activates CART positive neurons of the paraventricular nucleus in rats

    PubMed Central

    Noetzel, Steffen; Inhoff, Tobias; Goebel, Miriam; Taché, Yvette; Veh, Rüdiger W.; Bannert, Norbert; Grötzinger, Carsten; Wiedenmann, Bertram; Klapp, Burghard F.; Mönnikes, Hubert; Kobelt, Peter

    2014-01-01

    Cholecystokinin (CCK) plays a role in the short-term inhibition of food intake. Cocaine- and amphetamine-regulated transcript (CART) peptide has been observed in neurons of the paraventricular nucleus (PVN). It has been reported that intracerebroventricular injection of CART peptide inhibits food intake in rodents. The aim of the study was to determine whether intraperitoneally (ip) injected CCK-8S affects neuronal activity of PVN-CART neurons. Ad libitum fed male Sprague-Dawley rats received 6 or 10 μg/kg CCK-8S or 0.15 M NaCl ip (n = 4/group). The number of c-Fos-immunoreactive neurons was determined in the PVN, arcuate nucleus (ARC), and the nucleus of the solitary tract (NTS). CCK-8S dose-dependently increased the number of c-Fos-immunoreactive neurons in the PVN (mean ± SEM: 102 ± 6 vs. 150 ± 5 neurons/section, p < 0.05) and compared to vehicle treated rats (18 ± 7, p < 0.05 vs. 6 and 10 μg/kg CCK-8S). CCK-8S at both doses induced an increase in the number of c-Fos-immunoreactive neurons in the NTS (65 ± 13, p < 0.05, and 182 ± 16, p < 0.05). No effect on the number of c-Fos neurons was observed in the ARC. Immunostaining for CART and c-Fos revealed a dose-dependent increase of activated CART neurons (19 ± 3 vs. 29 ± 7; p < 0.05), only few activated CART neuron were observed in the vehicle group (1 ± 0). The present observation shows that CCK-8S injected ip induces an increase in neuronal activity in PVN-CART neurons and suggests that CART neurons in the PVN may play a role in the mediation of peripheral CCK-8S's anorexigenic effects. PMID:20307613

  7. Chronic intermittent hypoxia affects endogenous serotonergic inputs and expression of synaptic proteins in rat hypoglossal nucleus

    PubMed Central

    Wu, Xu; Lu, Huan; Hu, Lijuan; Gong, Wankun; Wang, Juan; Fu, Cuiping; Liu, Zilong; Li, Shanqun

    2017-01-01

    Evidence has shown that hypoxic episodes elicit hypoglossal neuroplasticity which depends on elevated serotonin (5-HT), in contrast to the rationale of obstructive sleep apnea (OSA) that deficient serotonergic input to HMs fails to keep airway patency. Therefore, understanding of the 5-HT dynamic changes at hypoglossal nucleus (HN) during chronic intermittent hypoxia (CIH) will be essential to central pathogenic mechanism and pharmacological therapy of OSA. Moreover, the effect of CIH on BDNF-TrkB signaling proteins was quantified in an attempt to elucidate cellular cascades/synaptic mechanisms following 5-HT alteration. Male rats were randomly exposed to normal air (control), intermittent hypoxia of 3 weeks (IH3) and 5 weeks (IH5) groups. Through electrical stimulation of dorsal raphe nuclei (DRN), we conducted amperometric technique with carbon fiber electrode in vivo to measure the real time release of 5-HT at XII nucleus. 5-HT2A receptors immunostaining measured by intensity and c-Fos quantified visually were both determined by immunohistochemistry. CIH significantly reduced endogenous serotonergic inputs from DRN to XII nucleus, shown as decreased peak value of 5-HT signals both in IH3 and IH5groups, whereas time to peak and half-life period of 5-HT were unaffected. Neither 5-HT2A receptors nor c-Fos expression in HN were significantly altered by CIH. Except for marked increase in phosphorylation of ERK in IH5 rats, BDNF-TrkB signaling and synaptophys consistently demonstrated downregulated levels. These results suggest that the deficiency of 5-HT and BDNF-dependent synaptic proteins in our CIH protocol contribute to the decompensated mechanism of OSA. PMID:28337282

  8. Development of Chemosensitivity in Neurons from the Nucleus Tractus Solitarii (NTS) of Neonatal Rats

    PubMed Central

    Conrad, Susan C.; Nichols, Nicole L.; Ritucci, Nick A.; Dean, Jay B.; Putnam, Robert W.

    2009-01-01

    We studied the development of chemosensitivity during the neonatal period in rat Nucleus tractus solitarii (NTS) neurons. We determined the percentage of neurons activated by hypercapnia (15% CO2) and assessed the magnitude of the response by calculating the chemosensitivity index (CI). There were no differences in the percentage of neurons that were inhibited (9%) or activated (44.8%) by hypercapnia or in the magnitude of the activated response (CI 164±4.9%) in NTS neurons from neonatal rats of all ages. To assess the degree of intrinsic chemosensitivity in these neurons we used chemical synaptic block medium and the gap junction blocker carbenoxolone. Chemical synaptic block medium slightly decreased basal firing rate but did not affect the percentage of NTS neurons that responded to hypercapnia at any neonatal age. However, in neonates aged rats of any age. In summary, the response of NTS neurons from neonatal rats appears to be intrinsic and largely unchanged throughout early development. In young neonates (

  9. Neural correlates for angular head velocity in the rat dorsal tegmental nucleus

    NASA Technical Reports Server (NTRS)

    Bassett, J. P.; Taube, J. S.; Oman, C. M. (Principal Investigator)

    2001-01-01

    Many neurons in the rat lateral mammillary nuclei (LMN) fire selectively in relation to the animal's head direction (HD) in the horizontal plane independent of the rat's location or behavior. One hypothesis of how this representation is generated and updated is via subcortical projections from the dorsal tegmental nucleus (DTN). Here we report the type of activity in DTN neurons. The majority of cells (75%) fired as a function of the rat's angular head velocity (AHV). Cells exhibited one of two types of firing patterns: (1) symmetric, in which the firing rate was positively correlated with AHV during head turns in both directions, and (2) asymmetric, in which the firing rate was positively correlated with head turns in one direction and correlated either negatively or not at all in the opposite direction. In addition to modulation by AHV, some of the AHV cells (40.1%) were weakly modulated by the rat's linear velocity, and a smaller number were modulated by HD (11%) or head pitch (15.9%). Autocorrelation analyses indicated that with the head stationary, AHV cells displayed irregular discharge patterns. Because afferents from the DTN are the major source of information projecting to the LMN, these results suggest that AHV information from the DTN plays a significant role in generating the HD signal in LMN. A model is proposed showing how DTN AHV cells can generate and update the LMN HD cell signal.

  10. Neural correlates for angular head velocity in the rat dorsal tegmental nucleus

    NASA Technical Reports Server (NTRS)

    Bassett, J. P.; Taube, J. S.; Oman, C. M. (Principal Investigator)

    2001-01-01

    Many neurons in the rat lateral mammillary nuclei (LMN) fire selectively in relation to the animal's head direction (HD) in the horizontal plane independent of the rat's location or behavior. One hypothesis of how this representation is generated and updated is via subcortical projections from the dorsal tegmental nucleus (DTN). Here we report the type of activity in DTN neurons. The majority of cells (75%) fired as a function of the rat's angular head velocity (AHV). Cells exhibited one of two types of firing patterns: (1) symmetric, in which the firing rate was positively correlated with AHV during head turns in both directions, and (2) asymmetric, in which the firing rate was positively correlated with head turns in one direction and correlated either negatively or not at all in the opposite direction. In addition to modulation by AHV, some of the AHV cells (40.1%) were weakly modulated by the rat's linear velocity, and a smaller number were modulated by HD (11%) or head pitch (15.9%). Autocorrelation analyses indicated that with the head stationary, AHV cells displayed irregular discharge patterns. Because afferents from the DTN are the major source of information projecting to the LMN, these results suggest that AHV information from the DTN plays a significant role in generating the HD signal in LMN. A model is proposed showing how DTN AHV cells can generate and update the LMN HD cell signal.

  11. Lesions of the entopeduncular nucleus in rats prevent apomorphine-induced deficient sensorimotor gating.

    PubMed

    Lütjens, Götz; Krauss, Joachim K; Schwabe, Kerstin

    2011-07-07

    Dopamine-induced hyperactivity and deficient sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR), are used as animal models for neuropsychiatric disorders such as schizophrenia and Tourette's syndrome. We here investigated whether excitotoxic lesions of the rat entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), would improve apomorphine-induced PPI-deficits and hyperactivity. Additionally, we investigated the effect of EPN lesions on cognition, motivation and motor skills. In male Sprague Dawley rats bilateral EPN lesions were induced by stereotactic injection of ibotenate (4 μg in 0.4 μl phosphate buffered saline, PBS) or sham-lesions by injection of vehicle PBS. After one week, rats were tested for learning and memory (continuous and delayed alternation, T-maze), for motivation (progressive ratio test with breakpoint of 3 min inactivity, Skinner box), and for motor skills (rotating rod). Thereafter, rats were tested for PPI of ASR (startle response system) after subcutaneous injection of apomorphine (1.0mg/kg and vehicle) and for locomotor activity (0.5mg/kg and vehicle). Ibotenate-induced EPN lesions did not affect learning and memory, motivation or motor skills. Basal locomotor activity and PPI was also not affected, but EPN lesions ameliorated apomorphine-induced hyperlocomotion and deficient PPI. This work indicates an important role of the EPN for the modulation of dopamine agonist-induced deficient sensorimotor gating and hyperlocomotion, without affecting normal behavioral function.

  12. Intermedin in paraventricular nucleus attenuates sympathetic activity and blood pressure via nitric oxide in hypertensive rats.

    PubMed

    Zhou, Ye-Bo; Sun, Hai-Jian; Chen, Dan; Liu, Tong-Yan; Han, Ying; Wang, Jue-Jin; Tang, Chao-Shu; Kang, Yu-Ming; Zhu, Guo-Qing

    2014-02-01

    Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide family, which shares the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs). This study investigated the effects of IMD in paraventricular nucleus (PVN) on renal sympathetic nerve activity and mean arterial pressure and its downstream mechanism in hypertension. Rats were subjected to 2-kidney 1-clip (2K1C) surgery to induce renovascular hypertension or sham operation. Acute experiments were performed 4 weeks later under anesthesia. IMD mRNA and protein were downregulated in 2K1C rats. Bilateral PVN microinjection of IMD caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in 2K1C rats than in sham-operated rats, which were prevented by pretreatment with adrenomedullin receptor antagonist AM22-52 or nonselective nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, and attenuated by selective neuronal NO synthase inhibitor N(ω)-propyl-l-arginine hydrochloride or endothelial NO synthase inhibitor N(5)-(1-iminoethyl)-l-ornithine dihydrochloride. AM22-52 increased renal sympathetic nerve activity and mean arterial pressure in 2K1C rats but not in sham-operated rats, whereas calcitonin/calcitonin gene-related peptide receptor antagonist calcitonin/calcitonin gene-related peptide 8-37 had no significant effect. CRLR and RAMP3 mRNA, as well as CRLR, RAMP2, and RAMP3 protein expressions, in the PVN were increased in 2K1C rats. Microinjection of IMD into the PVN increased the NO metabolites (NOx) level in the PVN in 2K1C rats, which was prevented by AM22-52. Chronic PVN infusion of IMD reduced, but AM22-52 increased, blood pressure in conscious 2K1C rats. These results indicate that IMD in the PVN inhibits sympathetic activity and attenuates hypertension in 2K1C rats, which are mediated by adrenomedullin receptors (CRLR/RAMP2 or CRLR/RAMP3) and its downstream NO.

  13. Tickling increases dopamine release in the nucleus accumbens and 50 kHz ultrasonic vocalizations in adolescent rats.

    PubMed

    Hori, Miyo; Shimoju, Rie; Tokunaga, Ryota; Ohkubo, Masato; Miyabe, Shigeki; Ohnishi, Junji; Murakami, Kazuo; Kurosawa, Mieko

    2013-03-27

    Adolescent rats emit 50 kHz ultrasonic vocalizations, a marker of positive emotion, during rough-and-tumble play or on tickling stimulation. The emission of 50 kHz ultrasonic vocalizations in response to tickling is suggested to be mediated by dopamine release in the nucleus accumbens; however, there is no direct evidence supporting this hypothesis. The present study aimed to elucidate whether play behavior (tickling) in adolescent rats can trigger dopamine release in the nucleus accumbens with hedonic 50 kHz ultrasonic vocalizations. The effect of tickling stimulation was compared with light-touch stimulation, as a discernible stimulus. We examined 35-40-day-old rats, which corresponds to the period of midadolescence. Tickling stimulation for 5 min significantly increased dopamine release in the nucleus accumbens (118±7% of the prestimulus control value). Conversely, light-touch stimulation for 5 min did not significantly change dopamine release. In addition, 50 kHz ultrasonic vocalizations were emitted during tickling stimulation but not during light-touch stimulation. Further, tickling-induced 50 kHz ultrasonic vocalizations were significantly blocked by the direct application of SCH23390 (D1 receptor antagonist) and raclopride (D2/D3 receptor antagonist) into the nucleus accumbens. Our study demonstrates that tickling stimulation in adolescent rats increases dopamine release in the nucleus accumbens, leading to the generation of 50 kHz ultrasonic vocalizations.

  14. Acquisition of an appetitive behavior prevents development of stress-induced neurochemical modifications in rat nucleus accumbens.

    PubMed

    Nanni, Giulio; Scheggi, Simona; Leggio, Benedetta; Grappi, Silvia; Masi, Flavio; Rauggi, Riccardo; De Montis, Maria Graziella

    2003-08-15

    In rats, exposure to chronic unavoidable stress produces a decrease in dopamine output in the nucleus accumbens shell that is accompanied by a decreased density of the dopamine transporter and an increased activity of the dopamine-D(1) receptor complex. These modifications have been hypothesized to be adaptive to decreased dopamine output in stressed rats. We investigated whether the learning of an appetitive behavior sustained by palatable food, which is associated with increased dopamine output in the nucleus accumbens shell as measured by microdialysis experiments, would affect the modifications induced by chronic stress exposure on dopamine transporter density and dopamine-D(1) receptor complex activity in the nucleus accumbens. Rats exposed to chronic unavoidable stress after acquisition of the appetitive behavior showed a higher dopamine extraneuronal release in the nucleus accumbens shell than that of stressed animals, and similar to that of control rats. Moreover, previous acquisition of the appetitive behavior prevented development of a stress-induced decrease in dopamine transporter density, measured by [(3)H]-WIN 35428 binding, a stress-induced increase in dopamine-D(1) receptor density, measured by binding of [(3)H]-SCH 23390, and SKF 38393-stimulated adenylyl cyclase activity in the nucleus accumbens. These results support the hypothesis that changes induced in pre- and postsynaptic dopaminergic transmission by chronic stress exposure are related to decreased dopamine output. Copyright 2003 Wiley-Liss, Inc.

  15. Dissociation of prefrontal cortex and nucleus accumbens dopaminergic systems in conditional learning in rats.

    PubMed

    George, David N; Jenkins, Trisha A; Killcross, Simon

    2011-11-20

    There is converging evidence that the prefrontal and mesolimbic dopaminergic (DAergic) systems are involved in the performance of a variety of tasks that require the use of contextual, or task-setting, information to select an appropriate response from a number of candidate responses. Performance on tasks of this nature are impaired in schizophrenia and in rats exposed to psychotomimetics; impairments that are often attenuated by administration of dopamine (DA) antagonists. Rats were trained on either a complex instrumental discrimination task, that required the use of task-setting cues, or a simple discrimination task that did not. Following training, microdialysis probes were implanted unilaterally in either the medial prefrontal cortex (mPFC) or nucleus accumbens (NAc) and samples were collected in freely moving animals during a behavioural test session. In Experiment 1, we found no difference in levels of DA in the mPFC of rats while they were performing the two discrimination tasks. Rats that performed the complex task did, however, show significantly higher mPFC DA levels relative to rats in the simple discrimination condition following the end of the behavioural test session. In Experiment 2, rats performing the conditional discrimination showed lower levels of DA in the NAc compared to the simple discrimination group both during the test session and after it. These results provide direct evidence that conditional discrimination tasks engage frontal and mesolimbic DAergic systems and are consistent with the proposal that regulation of fronto-striatal DA is involved in aspects of cognitive control that are known to be impaired in individuals with schizophrenia.

  16. Deafferentation of the hypothalamic paraventricular nucleus (PVN) exaggerates the sympathoadrenal system activity in stressed rats.

    PubMed

    Ondicova, K; Kvetnansky, R; Mravec, B

    2014-07-01

    The hypothalamic paraventricular nucleus is a key structure in the regulation of the autonomic and neuroendocrine systems response to acute and chronic stress challenges. In this study, we examined the effect of a mechanical posterolateral deafferentation of the PVN on the activity of sympathoadrenal system (SAS) and hypothalamo-pituitary-adrenal (HPA) axis by measuring plasma concentrations of epinephrine (EPI), norepinephrine (NE), and corticosterone (CORT) in rats exposed to acute immobilization (IMO) stress. The surgical posterolateral deafferentation of the PVN (PVN-deaf) was performed by Halasz knife, in brain of the adult male Sprague Dawley rats, according to coordinates of a stereotaxic atlas. Sham-operated (SHAM) animals underwent a craniotomy only. The animals were allowed to recover 14 days. Thereafter, the tail artery was cannulated and the animals exposed to acute IMO for 2 h. The blood samples were collected via cannula at the time points of 0, 5, 30, 60, and 120 min of the IMO. Concentrations of plasma EPI, NE, and CORT were determined by radioimmunoassay. The IMO-induced elevation of plasma EPI concentrations in the PVN-deaf rats reached statistical significance at 60 min of the IMO, when compared to SHAM rats. Similarly, the stress-induced elevation of the NE plasma levels in the PVN-deaf rats was significantly exaggerated at all time intervals of IMO in comparison with SHAM rats, whereas plasma CORT levels were significantly reduced. In contrast to the traditional view of excitatory role of the PVN in response to stress, our data indicate that some projections from the PVN to caudally localized hypothalamic structures, the brainstem or the spinal cord, exert inhibitory effect on the SAS system activity during acute IMO stress. The data indicate that stress-induced activation of the HPA axis is partially dependent on inputs from the brainstem to the PVN.

  17. [The role of neurochemical mechanisms of the dorsal raphe nucleus in various models of anxiety states in rats].

    PubMed

    Talalaenko, A N

    1989-01-01

    Dopamine and serotonin microinjection in the dorsal raphe nucleus of rats does not influence the alarm state in the test of "threatening situation" avoidance, but increases or weakens the state of alarm in the rest of "illuminated site" avoidance. Local injection of GABA in this midbrain formation weakens the alarm state in the test of "threatening situation" avoidance but is not effective in the test of "illuminated site" avoidance. Chemical stimulation of the raphe nucleus by glutaminic acid does not influence the two different experimentally modelled states of alarm, but modulates the mechanisms controlling the instinct of darkness preference by rats.

  18. The role of the ventrolateral nucleus of the thalamus in the switching of descending influences to motor activity in the rat.

    PubMed

    Fanardzhyan, V V; Papoyan, E V; Pogosyan, V I; Gevorkyan, O V

    2002-01-01

    Studies on rats showed that the facilitating influence of preliminary transection of the rubrospinal tract on recovery of motor activity and operant reflexes disrupted by lesioning of the red nucleus was more apparent when lesioning was chemical than when lesioning was electrolytic. This is due to the survival of cerebellothalamic fibers to the ventrolateral nucleus of the thalamus after chemical lesioning of the red nucleus with quinolinic acid. It was also shown that preliminary lesioning of the ventrolateral thalamic nucleus strongly hindered the switching of motor activity under the control of the corticospinal tract in rats subjected to section of the rubrospinal tract and lesioning of the red nucleus.

  19. Influence of fastigial nucleus stimulation on heart rate variability of surgically induced myocardial infarction rats: fastigial nucleus stimulation and autonomous nerve activity.

    PubMed

    Abulaiti, Alimujiang; Hu, Dayi; Zhu, Danian; Zhang, Runfeng

    2011-11-01

    Electrical stimulation of the rostal cerebellar fastigial nucleus (FNS) has been proved to have neuroprotective effects, but it is not known whether FNS also has a cardioprotective effect. One hundred Sprague-Dawley rats were randomly allocated into four groups, including a sham-operation group (Sham group), rats whose coronary arteries were ligated but the FNs were sham stimulated (AMI group), rats in which both coronary arteries were ligated and FNs were stimulated (FNS group), and rats whose fastigial nuclei were lesioned 5 days before ligation, then their coronary arteries were ligated and FNs were stimulated (FNL group). Heart rate variability parameters were monitored 6 h, 24 h, 7 days and 21 days after ligation, and mortality rates, hemodynamic parameters and infarction sizes were compared after 21 days. FNS improved the survival of rats, and this may be due to the increased vagal and decreased sympathetic tone. FN stimulation does not affect infarction size and hemodynamic parameters. FN stimulation may have a protective effect on surgically induced myocardial infarction rats.

  20. Clinical risk factors and periventricular leucomalacia.

    PubMed

    Trounce, J Q; Shaw, D E; Levene, M I; Rutter, N

    1988-01-01

    Two hundred infants of below 1501 g at birth were regularly examined with real time ultrasound using a 7.5 MHz transducer. Abnormalities were categorized as periventricular haemorrhage (PVH) (n = 107) or periventricular leucomalacia (PVL), with or without PVH (n = 52). Of the group with PVL, 25 had the appearances of prolonged flare without cavitation. Prospective assessments of up to 50 potential clinical risk factors were made wherever possible on each infant including stratification of all blood gas and systolic blood pressure data. Multivariate logistic regression analyses confirmed a strong correlation between immaturity and PVH but this was not found in cases of PVL. Independent variables associated with PVL included pneumothorax, maximum bilirubin concentration, surgery, and the proportion of time the infant's PaCO2 remained above 7 kPa. There was a very strong inverse correlation between anaemia and PVL. Systolic blood pressure data were carefully analysed and there was no relation between either hypotension or antepartum haemorrhage and the development of PVL.

  1. Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat

    PubMed Central

    Hosford, Patrick S.; Millar, Julian; Ramage, Andrew G.

    2017-01-01

    New Findings What is the central question of this study? Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity‐dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously. What is the main finding and its importance? Using fast‐cyclic voltammetry, we found that changes in local tissue PO2 in the nucleus tractus solitarii induced by electrical stimulation of the vagus nerve are significantly impaired in spontaneously hypertensive rats. This is consistent with previous observations showing that brainstem hypoxia plays an important role in the pathogenesis of arterial hypertension. The effects of arterial hypertension on cerebral blood flow remain poorly understood. Haemodynamic responses within the somatosensory cortex have been shown to be impaired in the spontaneously hypertensive rat (SHR) model. However, it is unknown whether arterial hypertension affects oxygen homeostasis in vital brainstem areas that control cardiovascular reflexes. In this study, we assessed vagus nerve stimulation‐induced changes in local tissue PO2 (PtO2) in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of PtO2 were performed using a novel application of fast‐cyclic voltammetry, which allows higher temporal resolution of O2 changes than traditional optical fluorescence techniques. Electrical stimulation of the central cut end of the vagus nerve (ESVN) caused profound reductions in arterial blood pressure along with biphasic changes in PtO2 in the cNTS, characterized by a rapid decrease in PtO2 (‘initial dip’) followed by a post‐stimulus overshoot above baseline. The initial dip was found to be significantly smaller in SHRs compared with normotensive Wistar rats even after ganglionic blockade. The post‐ESVN overshoot was similar in both groups but was reduced in Wistar rats after

  2. Activation of Neurokinin 3 Receptors in the Median Preoptic Nucleus Decreases Core Temperature in the Rat

    PubMed Central

    Dacks, Penny A.; Krajewski, Sally J.

    2011-01-01

    Estrogens have pronounced effects on thermoregulation, as illustrated by the occurrence of hot flushes secondary to estrogen withdrawal in menopausal women. Because neurokinin B (NKB) gene expression is markedly increased in the infundibular (arcuate) nucleus of postmenopausal women, and is modulated by estrogen withdrawal and replacement in multiple species, we have hypothesized that NKB neurons could play a role in the generation of flushes. There is no information, however, on whether the primary NKB receptor [neurokinin 3 receptor (NK3R)] modulates body temperature in any species. Here, we determine the effects of microinfusion of a selective NK3R agonist (senktide) into the rat median preoptic nucleus (MnPO), an important site in the heat-defense pathway. Senktide microinfusion into the rat MnPO decreased core temperature in a dose-dependent manner. The hypothermia induced by senktide was similar in ovariectomized rats with and without 17β-estradiol replacement. The hypothermic effect of senktide was prolonged in rats exposed to an ambient temperature of 29.0 C, compared with 21.5 C. Senktide microinfusion also altered tail skin vasomotion in rats exposed to an ambient temperature of 29.0 but not 21.5 C. Comparisons of the effects of senktide at different ambient temperatures indicated that the hypothermia was not secondary to thermoregulatory failure or a reduction in cold-induced thermogenesis. Other than a very mild increase in drinking, senktide microinfusion did not affect behavior. Terminal fluorescent dextran microinfusion showed targeting of the MnPO and adjacent septum, and immunohistochemical studies revealed that senktide induced a marked increase in Fos-activation in the MnPO. Because MnPO neurons expressed NK3R-immunoreactivity, the induction of MnPO Fos by senktide is likely a direct effect. By demonstrating that NK3R activation in the MnPO modulates body temperature, these studies support the hypothesis that hypothalamic NKB neurons could be

  3. Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat.

    PubMed

    Hosford, Patrick S; Millar, Julian; Ramage, Andrew G; Marina, Nephtali

    2017-04-01

    What is the central question of this study? Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity-dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously. What is the main finding and its importance? Using fast-cyclic voltammetry, we found that changes in local tissue PO2 in the nucleus tractus solitarii induced by electrical stimulation of the vagus nerve are significantly impaired in spontaneously hypertensive rats. This is consistent with previous observations showing that brainstem hypoxia plays an important role in the pathogenesis of arterial hypertension. The effects of arterial hypertension on cerebral blood flow remain poorly understood. Haemodynamic responses within the somatosensory cortex have been shown to be impaired in the spontaneously hypertensive rat (SHR) model. However, it is unknown whether arterial hypertension affects oxygen homeostasis in vital brainstem areas that control cardiovascular reflexes. In this study, we assessed vagus nerve stimulation-induced changes in local tissue PO2 (PtO2) in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of PtO2 were performed using a novel application of fast-cyclic voltammetry, which allows higher temporal resolution of O2 changes than traditional optical fluorescence techniques. Electrical stimulation of the central cut end of the vagus nerve (ESVN) caused profound reductions in arterial blood pressure along with biphasic changes in PtO2 in the cNTS, characterized by a rapid decrease in PtO2 ('initial dip') followed by a post-stimulus overshoot above baseline. The initial dip was found to be significantly smaller in SHRs compared with normotensive Wistar rats even after ganglionic blockade. The post-ESVN overshoot was similar in both groups but was reduced in Wistar rats after ganglionic blockade. In

  4. Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat.

    PubMed

    Pamenter, Matthew E; Carr, J Austin; Go, Ariel; Fu, Zhenxing; Reid, Stephen G; Powell, Frank L

    2014-04-15

    When exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. Currently these mechanisms of HVR plasticity are unknown and we hypothesized that they involve glutamatergic synapses in the nucleus tractus solitarius (NTS), where afferent endings from arterial chemoreceptors terminate. To test this, we treated rats held in normoxia (CON) or 10% O2 (CSH) for 7 days and measured ventilation in conscious, unrestrained animals before and after microinjecting glutamate receptor agonists and antagonists into the NTS. In normoxia, AMPA increased ventilation 25% and 50% in CON and CSH, respectively, while NMDA doubled ventilation in both groups (P < 0.05). Specific AMPA and NMDA receptor antagonists (NBQX and MK801, respectively) abolished these effects. MK801 significantly decreased the HVR in CON rats, and completely blocked the acute HVR in CSH rats but had no effect on ventilation in normoxia. NBQX decreased ventilation whenever it was increased relative to normoxic controls; i.e. acute hypoxia in CON and CSH, and normoxia in CSH. These results support our hypothesis that glutamate receptors in the NTS contribute to plasticity in the HVR with CSH. The mechanism underlying this synaptic plasticity is probably glutamate receptor modification, as in CSH rats the expression of phosphorylated NR1 and GluR1 proteins in the NTS increased 35% and 70%, respectively, relative to that in CON rats.

  5. Apoptosis, senescence, and autophagy in rat nucleus pulposus cells: Implications for diabetic intervertebral disc degeneration.

    PubMed

    Jiang, Libo; Zhang, Xiaolei; Zheng, Xuhao; Ru, Ao; Ni, Xiao; Wu, Yaosen; Tian, Naifeng; Huang, Yixing; Xue, Enxing; Wang, Xiangyang; Xu, Huazi

    2013-05-01

    This research was aimed to study the mechanisms by which diabetes aggravates intervertebral disc degeneration (IDD) and to discuss the relationship between autophagy and IDD in nucleus pulposus (NP) cells. Sixteen weeks after injecting streptozotocin (STZ), the intervertebral discs (IVDs) were studied by histology, Alcian blue, 1,9-dimethylmethylene blue (DMMB), immunohistochemistry, and RT-PCR to explore the IDD. The apoptosis and senescence of NP cells was investigated by terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, immunohistochemistry, and Western blot for caspase3, caspase8, caspase9, and p16lnk4A (increased in cellular senescence). The level of autophagy in NP cells was detected by Western blot, immunohistochemistry, and transmission electron microscopy (TEM). The proteoglycan and collagen II in the extracellular matrix and the aggrecan and collagen II mRNA expression in NP cells of diabetic rats were decreased compared with the control group. Diabetes increased apoptosis of NP cells and led to activations of initiators of intrinsic (caspases-9) and extrinsic (caspase-8) pathways as well as their common executioner (caspase-3). Cellular senescence was increased about twofold in NP of diabetic rats. In addition, the Western blot, immunohistochemistry, and TEM demonstrated higher level of autophagy in NP cells of diabetic rats than control rats to a statistically significant extent. These findings support that diabetes induced by STZ can cause IDD by accelerating the apoptosis and senescence of NP cells excluding the overweight influence. And the results suggest that the autophagy may be a response mechanism to the change of NP cells in diabetic rats. Copyright © 2012 Orthopaedic Research Society.

  6. Anatomical and functional connections between the locus coeruleus and the nucleus tractus solitarius in neonatal rats

    PubMed Central

    Lopes, Luana T.; Patrone, Luis Gustavo A.; Li, Ke-Yong; Imber, Ann N.; Graham, Cathy D.; Gargaglioni, Luciane H.; Putnam, Robert W.

    2016-01-01

    This study was designed to investigate brain connections among chemosensitive areas in newborn rats. Rhodamine beads were injected unilaterally into the locus coeruleus (LC) or into the caudal part of the nucleus tractus solitarius (cNTS) in Sprague-Dawley rat pups (P7–P10). Rhodamine-labeled neurons were patched in brainstem slices to study their electrophysiological responses to hypercapnia and to determine if chemosensitive neurons are communicating between LC and cNTS regions. After 7–10 days, retrograde labeling was observed in numerous areas of the brainstem, including many chemosensitive regions, such as the contralateral LC, cNTS and medullary raphe. Whole-cell patch clamp was done in cNTS. In 4 of 5 retrogradely-labeled cNTS neurons that projected to the LC, firing rate increased in response to hypercapnic acidosis (15% CO2), even in synaptic blockade medium (high Mg2+/low Ca2+). In contrast, 2 of 3 retrogradely-labeled LC neurons that projected to cNTS had reduced firing rate in response to hypercapnic acidosis, both in the presence and absence of synaptic blockade medium. Extensive anatomical connections among chemosensitive brainstem regions in newborn rats were found and at least for the LC and cNTS, the connections involve some CO2-sensitive neurons. Such anatomical and functional coupling suggests a complex central respiratory control network, such as seen in adult rats, is already largely present in neonatal rats by at least day P7–P10. Since the NTS and the LC play a major role in memory consolidation, our results may also contribute to the understanding of the development of memory consolidation. PMID:27001176

  7. Anatomical and functional connections between the locus coeruleus and the nucleus tractus solitarius in neonatal rats.

    PubMed

    Lopes, L T; Patrone, L G A; Li, K-Y; Imber, A N; Graham, C D; Gargaglioni, L H; Putnam, R W

    2016-06-02

    This study was designed to investigate brain connections among chemosensitive areas in newborn rats. Rhodamine beads were injected unilaterally into the locus coeruleus (LC) or into the caudal part of the nucleus tractus solitarius (cNTS) in Sprague-Dawley rat pups (P7-P10). Rhodamine-labeled neurons were patched in brainstem slices to study their electrophysiological responses to hypercapnia and to determine if chemosensitive neurons are communicating between LC and cNTS regions. After 7-10 days, retrograde labeling was observed in numerous areas of the brainstem, including many chemosensitive regions, such as the contralateral LC, cNTS and medullary raphe. Whole-cell patch clamp was done in cNTS. In 4 of 5 retrogradely labeled cNTS neurons that projected to the LC, firing rate increased in response to hypercapnic acidosis (15% CO2), even in synaptic blockade medium (SNB) (high Mg(2+)/low Ca(2+)). In contrast, 2 of 3 retrogradely labeled LC neurons that projected to cNTS had reduced firing rate in response to hypercapnic acidosis, both in the presence and absence of SNB. Extensive anatomical connections among chemosensitive brainstem regions in newborn rats were found and at least for the LC and cNTS, the connections involve some CO2-sensitive neurons. Such anatomical and functional coupling suggests a complex central respiratory control network, such as seen in adult rats, is already largely present in neonatal rats by at least day P7-P10. Since the NTS and the LC play a major role in memory consolidation, our results may also contribute to the understanding of the development of memory consolidation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Plasticity at Glycinergic Synapses in Dorsal Cochlear Nucleus (DCN) of Rats with Behavioral Evidence of Tinnitus

    PubMed Central

    Wang, Hongning; Brozoski, Thomas J.; Turner, Jeremy G.; Ling, Lynne; Parrish, Jennifer L.; Hughes, Larry F.; Caspary, Donald M.

    2009-01-01

    Fifteen to 35% of the United States population experiences tinnitus, a subjective “ringing in the ears”. Up to 10 percent of those afflicted report severe and disabling symptoms. Tinnitus was induced in rats using unilateral, one-hour, 17 kHz-centered octave-band noise (116 dB SPL) and assessed using a gap-startle method. The dorsal cochlear nucleus (DCN) is thought to undergo plastic changes suggestive of altered inhibitory function during tinnitus development. Exposed rats showed near pre-exposure ABR thresholds for clicks and all tested frequencies 16 weeks post-exposure. Sound-exposed rats showed significantly worse gap detection at 24 and 32 kHz 16 weeks following sound exposure, suggesting the development of chronic, high frequency tinnitus. Message and protein levels of α1–3, and β glycine receptor subunits (GlyRs), and the anchoring protein, gephyrin, were measured in DCN fusiform cells 4 months following sound exposure. Rats with evidence of tinnitus showed significant GlyR α1 protein decreases in the middle and high frequency regions of the DCN while α1 message levels were paradoxically increased. Gephyrin levels showed significant tinnitus-related increases in sound-exposed rats suggesting intracellular receptor trafficking changes following sound exposure. Consistent with decreased α1 subunit protein levels, strychnine binding studies showed significant tinnitus-related decreases in the number of GlyR binding sites, supporting tinnitus-related changes in the number and/or composition of GlyRs. Collectively, these findings suggest the development of tinnitus is likely associated with functional GlyR changes in DCN fusiform cells consistent with previously described behavioral and neurophysiologic changes. Tinnitus related GlyR changes could provide a unique receptor target for tinnitus pharmacotherapy or blockade of tinnitus initiation. PMID:19699270

  9. Reproductive experience increases prolactin responsiveness in the medial preoptic area and arcuate nucleus of female rats.

    PubMed

    Anderson, Greg M; Grattan, David R; van den Ancker, Willemijn; Bridges, Robert S

    2006-10-01

    The experience of pregnancy plus lactation produces long-term enhancements in maternal behavior as well as reduced secretion of prolactin, a key hormone for the initial establishment of maternal care. Given that prolactin acts centrally to induce maternal care as well as regulate its own secretion, we tested whether prolactin receptors in brain regions known to regulate behavioral and neuroendocrine processes were up-regulated and more responsive to prolactin in reproductively experienced females. Diestrous primiparous (8 wk after weaning) and age-matched virgin rats were treated with 250 microg ovine prolactin sc or vehicle and the brains collected 2 h later for measurement of mRNA for genes involved in prolactin signaling. Reproductively experienced rats had lower serum prolactin concentrations, compared with virgin rats, suggesting enhanced prolactin feedback on the arcuate neurons regulating prolactin secretion. In the medial preoptic area and arcuate nucleus (regions involved in regulating maternal behavior and prolactin secretion, respectively), the level of long-form prolactin receptor mRNA was higher in primiparous rats, and prolactin treatment induced a further increase in receptor expression in these animals. In the same regions, suppressors of cytokine signaling-1 and -3 mRNA levels were also markedly increased after prolactin treatment in reproductively experienced but not virgin rats. These results support the idea that reproductive experience increases central prolactin responsiveness. The induction of prolactin receptors and enhanced prolactin responsiveness as a result of pregnancy and lactation may help account for the retention of maternal behavior and shifts in prolactin secretion in reproductively experienced females.

  10. Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat

    PubMed Central

    Pamenter, Matthew E; Carr, J Austin; Go, Ariel; Fu, Zhenxing; Reid, Stephen G; Powell, Frank L

    2014-01-01

    When exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. Currently these mechanisms of HVR plasticity are unknown and we hypothesized that they involve glutamatergic synapses in the nucleus tractus solitarius (NTS), where afferent endings from arterial chemoreceptors terminate. To test this, we treated rats held in normoxia (CON) or 10% O2 (CSH) for 7 days and measured ventilation in conscious, unrestrained animals before and after microinjecting glutamate receptor agonists and antagonists into the NTS. In normoxia, AMPA increased ventilation 25% and 50% in CON and CSH, respectively, while NMDA doubled ventilation in both groups (P < 0.05). Specific AMPA and NMDA receptor antagonists (NBQX and MK801, respectively) abolished these effects. MK801 significantly decreased the HVR in CON rats, and completely blocked the acute HVR in CSH rats but had no effect on ventilation in normoxia. NBQX decreased ventilation whenever it was increased relative to normoxic controls; i.e. acute hypoxia in CON and CSH, and normoxia in CSH. These results support our hypothesis that glutamate receptors in the NTS contribute to plasticity in the HVR with CSH. The mechanism underlying this synaptic plasticity is probably glutamate receptor modification, as in CSH rats the expression of phosphorylated NR1 and GluR1 proteins in the NTS increased 35% and 70%, respectively, relative to that in CON rats. PMID:24492841

  11. The role of neurotensin in positive reinforcement in the rat central nucleus of amygdala.

    PubMed

    László, Kristóf; Tóth, Krisztián; Kertes, Erika; Péczely, László; Lénárd, László

    2010-04-02

    In the central nervous system neurotensin (NT) acts as a neurotransmitter and neuromodulator. It was shown that NT has positive reinforcing effects after its direct microinjection into the ventral tegmental area. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, regulation of feeding, anxiety and emotional behavior. By means of immunohistochemical and radioimmune methods it was shown that the amygdaloid body is relatively rich in NT immunoreactive elements and NT receptors. The aim of our study was to examine the possible effects of NT on reinforcement and anxiety in the CeA. In conditioned place preference test male Wistar rats were microinjected bilaterally with 100 or 250 ng NT in volume of 0.4 microl or 35 ng neurotensin receptor 1 (NTS1) antagonist SR 48692 alone, or NTS1 antagonist 15 min before 100 ng NT treatment. Hundred or 250 ng NT significantly increased the time rats spent in the treatment quadrant. Prior treatment with the non-peptide NTS1 antagonist blocked the effects of NT. Antagonist itself did not influence the reinforcing effect. In elevated plus maze test we did not find differences among the groups as far as the anxiety index (time spent on the open arms) was concerned. Our results suggest that in the rat ACE NT has positive reinforcing effects. We clarified that NTS1s are involved in this action. It was also shown that NT does not influence anxiety behavior.

  12. Diurnal regulation of per repeat family in the suprachiasmatic nucleus of rat brain.

    PubMed

    Ishida, N; Nishimatsu, S; Matsui, M; Mitsui, Y; Nohno, T; Shibata, N; Noji, S

    1994-01-01

    We have recently reported fluctuations in the expression of the period repeat sequence, pp2.5, during light-dark cycles in the suprachiasmatic nucleus (SCN) of rat. Presently, we performed in situ hybridization which shows that the fluctuation of pp2.5 expression continues during constant darkness conditions in the SCN of rat. The light exposure during subjective night but not subjective day triggered its elevated expression in a time-dependent manner which is parallel to that of c-fos expression. In this review, the cloning and characterization of multiple per repeat sequences from mouse genom and rat brain mRNA were summarized. The abundance of a novel per repeat mRNA (designated as RB15) fluctuates during a light-dark cycle in the SCN. These findings suggest that per repeat sequence may have a role for the mammalian circadian rhythms. The evolutionary relationship between the mammarian per repeat sequence and the Drosophila period gene is also discussed.

  13. Nucleus accumbens deep brain stimulation in a rat model of binge eating.

    PubMed

    Doucette, W T; Khokhar, J Y; Green, A I

    2015-12-15

    Binge eating (BE) is a difficult-to-treat behavior with high relapse rates, thus complicating several disorders including obesity. In this study, we tested the effects of high-frequency deep brain stimulation (DBS) in a rodent model of BE. We hypothesized that BE rats receiving high-frequency DBS in the nucleus accumbens (NAc) core would have reduced binge sizes compared with sham stimulation in both a 'chronic BE' model as well as in a 'relapse to chronic BE' model. Male Sprague-Dawley rats (N=18) were implanted with stimulating electrodes in bilateral NAc core, and they received either active stimulation (N=12) or sham stimulation (N=6) for the initial chronic BE experiments. After testing in the chronic BE state, rats did not engage in binge sessions for 1 month, and then resumed binge sessions (relapse to chronic BE) with active or sham stimulation (N=5-7 per group). A significant effect of intervention group was observed on binge size in the chronic BE state, but no significant difference between intervention groups was observed in the relapse to chronic BE experiments. This research, making use of both a chronic BE model as well as a relapse to chronic BE model, provides data supporting the hypothesis that DBS of the NAc core can decrease BE. Further research will be needed to learn how to increase the effect size and decrease deep brain stimulation-treatment outcome variability across the continuum of BE behavior.

  14. The medial amygdaloid nucleus modulates the baroreflex activity in conscious rats.

    PubMed

    Fortaleza, Eduardo Albino Trindade; Ferreira-Junior, Nilson Carlos; Lagatta, Davi Campos; Resstel, Leonardo Barbosa Moraes; Corrêa, Fernando Morgan Aguiar

    2015-12-01

    The medial amygdaloid nucleus (MeA) is involved in cardiovascular control. In the present study we report the effect of MeA pharmacological ablations caused by bilateral microinjections of the nonselective synaptic blocker CoCl2 on cardiac baroreflex responses in rats. MeA synaptic inhibition evoked by local bilateral microinjection of 100 nL of CoCl2 (1 mM) did not affect blood pressure or heart rate baseline, suggesting no tonic MeA influence on resting cardiovascular parameters. However, 10 min after CoCl2 microinjection into the MeA of male Wistar rats, the reflex bradycardic response evoked by intravenous infusion of phenylephrine was significantly enhanced when compared with the reflex bradycardic response observed before CoCl2. The treatment did not affect the tachycardic responses to the intravenous infusion of sodium nitroprusside (SNP). Baroreflex activity returned to control values 60 min after CoCl2 microinjections, confirming a reversible blockade. The present results indicate an involvement of the MeA in baroreflex modulation, suggesting that synapses in the MeA have an inhibitory influence on the bradycardic component of the baroreflex in conscious rats.

  15. Corticotropin-releasing hormone in the lateral parabrachial nucleus inhibits sodium appetite in rats.

    PubMed

    De Castro e Silva, Emilio; Fregoneze, Josmara B; Johnson, Alan Kim

    2006-04-01

    The present study investigated the role of corticotropin-releasing hormone (CRH) in the lateral parabrachial nucleus (LPBN) in the behavioral control of body fluid homeostasis by determining the effect of bilateral injections of the CRH receptor antagonist, alpha-helical corticotropin-releasing factor (CRF)(9-41), and the CRH receptor agonist, CRH, on sodium chloride (salt appetite) and water (thirst) intake. Groups of adult, male Sprague-Dawley rats had stainless-steel cannulas implanted bilaterally into the LPBN and were sodium depleted or water deprived. Bilateral injections of alpha-helical CRF(9-41) into the LPBN significantly potentiated water and salt intake in the sodium-depleted rats when access to fluids was restored. Bilateral injections of alpha-helical CRF(9-41) into the LPBN (1.0 microg) also increased sodium appetite in water-deprived rats. Conversely, in sodium-depleted animals, bilateral injections of CRH inhibited sodium chloride intake. These results suggest that there is an endogenous CRH inhibitory mechanism operating in the LPBN to modulate the intake of sodium (salt appetite). This mechanism may contribute to the behavioral control of restoration of body fluid homeostasis in sodium-deficient states.

  16. Automated detection of periventricular veins on 7 T brain MRI

    NASA Astrophysics Data System (ADS)

    Kuijf, Hugo J.; Bouvy, Willem H.; Zwanenburg, Jaco J. M.; Viergever, Max A.; Biessels, Geert Jan; Vincken, Koen L.

    2015-03-01

    Cerebral small vessel disease is common in elderly persons and a leading cause of cognitive decline, dementia, and acute stroke. With the introduction of ultra-high field strength 7.0T MRI, it is possible to visualize small vessels in the brain. In this work, a proof-of-principle study is conducted to assess the feasibility of automatically detecting periventricular veins. Periventricular veins are organized in a fan-pattern and drain venous blood from the brain towards the caudate vein of Schlesinger, which is situated along the lateral ventricles. Just outside this vein, a region-of- interest (ROI) through which all periventricular veins must cross is defined. Within this ROI, a combination of the vesselness filter, tubular tracking, and hysteresis thresholding is applied to locate periventricular veins. All detected locations were evaluated by an expert human observer. The results showed a positive predictive value of 88% and a sensitivity of 95% for detecting periventricular veins. The proposed method shows good results in detecting periventricular veins in the brain on 7.0T MR images. Compared to previous works, that only use a 1D or 2D ROI and limited image processing, our work presents a more comprehensive definition of the ROI, advanced image processing techniques to detect periventricular veins, and a quantitative analysis of the performance. The results of this proof-of-principle study are promising and will be used to assess periventricular veins on 7.0T brain MRI.

  17. Resveratrol attenuates inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis neurons associated with hyperalgesia in rats.

    PubMed

    Sekiguchi, Kenta; Takehana, Shiori; Shibuya, Eri; Matsuzawa, Nichiwa; Hidaka, Shiori; Kanai, Yurie; Inoue, Maki; Kubota, Yoshiko; Shimazu, Yoshihito; Takeda, Mamoru

    2016-01-01

    Resveratrol, a component of red wine, has been reported to decrease prostaglandin E2 production by inhibiting the cyclooxygenase-2 cascade and to modulate various voltage-dependent ion channels, suggesting that resveratrol could attenuate inflammatory hyperalgesia. However, the effects of resveratrol on inflammation-induced hyperexcitability of nociceptive neurons in vivo remain to be determined. Thus, the aim of the present study was to determine whether daily systemic administration of resveratrol to rats attenuates the inflammation-induced hyperexcitability of spinal trigeminal nucleus caudalis wide-dynamic range neurons associated with hyperalgesia. Inflammation was induced by injection of complete Freund's adjuvant into the whisker pad. The threshold of escape from mechanical stimulation applied to whisker pad in inflamed rats was significantly lower than in control rats. The decreased mechanical threshold in inflamed rats was restored to control levels by daily systemic administration of resveratrol (2 mg/kg, i.p.). The mean discharge frequency of spinal trigeminal nucleus caudalis wide-dynamic range neurons to both nonnoxious and noxious mechanical stimuli in inflamed rats was significantly decreased after resveratrol administration. In addition, the increased mean spontaneous discharge of spinal trigeminal nucleus caudalis wide-dynamic range neurons in inflamed rats was significantly decreased after resveratrol administration. Similarly, resveratrol significantly diminished noxious pinch-evoked mean after discharge frequency and occurrence in inflamed rats. Finally, resveratrol restored the expanded mean size of the receptive field in inflamed rats to control levels. These results suggest that chronic administration of resveratrol attenuates inflammation-induced mechanical inflammatory hyperalgesia and that this effect is due primarily to the suppression of spinal trigeminal nucleus caudalis wide dynamic range neuron hyperexcitability via inhibition of

  18. Activation of neurons in the hypothalamic dorsomedial nucleus via hypothalamic projections of the nucleus of the solitary tract following refeeding of fasted rats.

    PubMed

    Renner, Eva; Szabó-Meltzer, Kinga I; Puskás, Nela; Tóth, Zsuzsanna E; Dobolyi, Arpád; Palkovits, Miklós

    2010-01-01

    We report that satiation evokes neuronal activity in the ventral subdivision of the hypothalamic dorsomedial nucleus (DMH) as indicated by increased c-fos expression in response to refeeding in fasted rats. The absence of significant Fos activation following food presentation without consumption suggests that satiation but not craving for food elicits the activation of ventral DMH neurons. The distribution pattern of the prolactin-releasing peptide (PrRP)-immunoreactive (ir) network showed remarkable correlations with the distribution of activated neurons within the DMH. The PrRP-ir fibers and terminals were immunolabeled with tyrosine hydroxylase, suggesting their origin in lower brainstem instead of local, hypothalamic PrRP cells. PrRP-ir fibers arising from neurons of the nucleus of the solitary tract could be followed to the hypothalamus. Unilateral transections of these fibers at pontine and caudal hypothalamic levels resulted in a disappearance of the dense PrRP-ir network in the ventral DMH while PrRP immunoreactivity was increased in transected fibers caudal to the knife cuts as well as in perikarya of the nucleus of the solitary tract ipsilateral to the transections. In accord with these changes, the number of Fos-expressing neurons following refeeding declined in the ipsilateral but remained high in the contralateral DMH. However, the Fos response in the ventral DMH was not attenuated following chemical lesion (neonatal monosodium glutamate treatment) of the hypothalamic arcuate nucleus, another possible source of DMH inputs. These findings suggest that PrRP projections from the nucleus of the solitary tract contribute to the activation of ventral DMH neurons during refeeding, possibly by transferring information on cholecystokinin-mediated satiation.

  19. Effect of glutamate stimulation of the cuneiform nucleus on cardiovascular regulation in anesthetized rats: role of the pontine Kolliker-Fuse nucleus.

    PubMed

    Shafei, Mohammad Naser; Nasimi, Ali

    2011-04-18

    Cuneiform nucleus (CnF) is a reticular nucleus of the midbrain involved in cardiovascular function and stress. There is no report on the cardiovascular effects of the glutamatergic system in the CnF. In the present study, we investigated the cardiovascular effects of glutamate and its NMDA and AMPA/kainate receptors in the CnF. In addition, the possible mediation of Kolliker-Fuse (KF) nucleus in the cardiovascular effects of the CnF was explored. l-glutamate, AP5 (an NMDA receptor antagonist), and CNQX (an AMPA/kainate receptor antagonist) (50-100 nl) were microinjected into the CnF of anesthetized rats. Also, the KF was blocked by cobalt chloride (CoCl(2)) then l-glutamate was microinjected into the CnF. The maximum changes of blood pressure and heart rate were compared with the pre-injection (paired t-test) and control (independent t-test) values. Microinjection of glutamate (25 nmol/100 nl) into the CnF produced either a short pressor and bradycardic or a long pressor and tachycardic responses. Microinjection of AP5 or CNQX alone did not affect the basal arterial pressure and heart rate. However, co-injection of glutamate with AP5 strongly attenuated the short and moderately attenuated the long cardiovascular responses elicited by glutamate. Co-injection of glutamate with CNQX did not attenuate the short and weakly attenuated the long cardiovascular responses elicited by glutamate. These data suggest that the responses are mediated mainly through NMDA receptors. Blockade of the KF nucleus strongly attenuated the short response and weakly attenuated the long response to glutamate microinjection, suggesting that the cardiovascular effects of glutamate in the CnF, especially the short responses, were mediated by the KF nucleus. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Systemic leptin increases the electrical activity of supraoptic nucleus oxytocin neurones in virgin and late pregnant rats.

    PubMed

    Velmurugan, S; Russell, J A; Leng, G

    2013-04-01

    In the rat hypothalamus, fasting attenuates the expression of oxytocin and this can be reversed by exogenous leptin administration. In the present study, we investigated the effects of systemically administered leptin on the electrical activity of magnocellular neurones in the supraoptic nucleus of urethane-anaesthetised rats. In virgin female rats, systemic leptin significantly excited identified oxytocin neurones with no detected effects on the patterning of activity, as reflected by hazard function analyses. The lowest dose that was consistently effective was 100 μg/i.v., and this dose had no significant effect on vasopressin neurones. In virgin rats fasted overnight, the spontaneous firing rate of oxytocin neurones was significantly lower than in unfasted rats, although leptin had a similar excitatory effect as in unfasted rats. In late pregnant rats (days 19-21 of pregnancy), spontaneous firing rates of oxytocin neurones were higher than in virgins, and the initial response to leptin was similar to that in virgin rats, although the increase in activity was more persistent. In fasted pregnant rats, the mean spontaneous firing rate of oxytocin neurones was again lower than in unfasted rats, although leptin had no significant effect even at the higher dose of 1 mg/rat. Thus, fasting reduced the spontaneous firing rates of oxytocin neurones in nonpregnant rats, and this effect could be reversed by the excitatory effects of leptin. Pregnant rats showed some evidence of leptin resistance but only after an overnight fast. © 2012 British Society for Neuroendocrinology.

  1. Elucidation of the anatomy of a satiety network: Focus on connectivity of the parabrachial nucleus in the adult rat.

    PubMed

    Zséli, Györgyi; Vida, Barbara; Martinez, Anais; Lechan, Ronald M; Khan, Arshad M; Fekete, Csaba

    2016-10-01

    We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c-Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well-known feeding-related brain regions such as the arcuate, dorsomedial, and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of the solitary tract and central amygdalar nucleus, other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin to understand the connectivity of the satiety network, the interconnectivity of PB with other refeeding-activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding-activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of the solitary tract. Axons originating from the PB were observed to closely associate with refeeding-activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of the solitary tract. These data indicate that the PB has bidirectional connections with most refeeding-activated neuronal groups, suggesting that short-loop feedback circuits exist in this satiety network. J. Comp. Neurol. 524:2803-2827, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley

  2. Elucidation of the Anatomy of a Satiety Network: Focus on Connectivity of the Parabrachial Nucleus in the Adult Rat

    PubMed Central

    Zséli, Györgyi; Vida, Barbara; Martinez, Anais; Lechan, Ronald M.; Khan, Arshad M.; Fekete, Csaba

    2017-01-01

    We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c-Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well-known feeding-related brain regions such as the arcuate, dorsomedial and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of solitary tract and central amygdalar nucleus; other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin understanding the connectivity of the satiety network, the interconnectivity of PB with other refeeding-activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding-activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of solitary tract. Axons originating from PB were observed to closely associate with refeeding-activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of solitary tract. These data indicate that the PB has bidirectional connections with most refeeding-activated neuronal groups, suggesting that short loop feedback circuits exist in this satiety network. PMID:26918800

  3. Effects of acute and chronic clozapine on dopamine release and metabolism in the striatum and nucleus accumbens of conscious rats.

    PubMed

    Invernizzi, R; Morali, F; Pozzi, L; Samanin, R

    1990-08-01

    1. The effect of single and repeated (once daily for 23 days) oral doses of 20 and 60 mg kg-1 clozapine on dopamine release and metabolism were studied by intracerebral dialysis in the striatum and nucleus accumbens of conscious rats. 2. The basal output of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and nucleus accumbens of rats given clozapine 20 or 60 mg kg-1 chronically, measured one day after the last drug dose, was not significantly different from that of vehicle-treated animals. 3. Challenge doses of 20 or 60 mg kg-1 clozapine produced similar increases in dopamine levels in the striatum and nucleus accumbens of animals which had received vehicle or clozapine 20 or 60 mg kg-1 once daily for 23 days, except that 1 h after administration 60 mg kg-1 clozapine had a greater effect in the nucleus accumbens. 4. In animals treated chronically with clozapine 20 and 60 mg kg-1 or vehicle, DOPAC levels in the striatum and nucleus accumbens were increased to the same extent by challenge doses of clozapine (20 or 60 mg kg-1). In animals treated chronically with clozapine, a challenge dose of 60 mg kg-1 had significantly greater effect on HVA only in the nucleus accumbens. 5. When DOPAC and HVA were measured post mortem in the striatum and nucleus accumbens 2 h after various oral doses of clozapine, it was found that 10 mg kg-1 significantly increased dopamine metabolites only in the nucleus accumbens whereas 100 mg kg-1 had this effect in both regions. Clozapine, 30mgkg-' significantly raised DOPAC levels in both regions but HVA was elevated only in the nucleus accumbens. 6. There appeared to be no appreciable changes in dopamine release and metabolism nor any reduction in the effect of clozapine in the nucleus accumbens after chronic drug treatment. In fact the effect was greater in chronically treated rats, particularly in the nucleus accumbens of animals given 60mgkg' clozapine. 7. It was confirmed that measurement of

  4. Electric stimulation of periventricular heterotopia: participation in higher cerebral functions.

    PubMed

    Wagner, Jan; Elger, Christian E; Urbach, Horst; Bien, Christian G

    2009-02-01

    Gray matter heterotopia are a common cause of pharmacoresistant epilepsy. Recently, several case studies have addressed the question of whether heterotopia can contribute to physiological cerebral functions. We describe two cases that demonstrate a functional role for periventricular heterotopia in higher cognitive processes. During presurgical diagnostics, two patients underwent electric stimulation of both the periventricular heterotopia and the overlying cortex. This revealed a functional role of periventricular heterotopia in higher cerebral functions such as language and complex visual and acoustic processing. Furthermore, stimulation of the overlying cortex led to unusually intense positive phenomena, including complex acoustic and gustatory hallucinations and language production. These cases illustrate that periventricular heterotopic neurons can contribute to higher cerebral functions. Interestingly, the anterior-to-posterior representation of these functions is comparable to the normal anterior-to-posterior representation in a normal neocortex (similar to a periventricular "minicortex" in early developmental stages).

  5. GFAP immunoreactivity within the rat nucleus ambiguus after laryngeal nerve injury

    PubMed Central

    Berdugo-Vega, G; Arias-Gil, G; Rodriguez-Niedenführ, M; Davies, D C; Vázquez, T; Pascual-Font, A

    2014-01-01

    Changes that occur in astroglial populations of the nucleus ambiguus after recurrent (RLN) or superior (SLN) laryngeal nerve injury have hitherto not been fully characterised. In the present study, rat RLN and SLN were lesioned. After 3, 7, 14, 28 or 56 days of survival, the nucleus ambiguus was investigated by means of glial fibrillary acidic protein (GFAP) immunofluorescence or a combination of GFAP immunofluorescence and the application of retrograde tracers. GFAP immunoreactivity was significantly increased 3 days after RLN resection and it remained significantly elevated until after 28 days post injury (dpi). By 56 dpi it had returned to basal levels. In contrast, following RLN transection with repair, GFAP immunoreactivity was significantly elevated at 7 dpi and remained significantly elevated until 14 dpi. It had returned to basal levels by 28 dpi. Topographical analysis of the distribution of GFAP immunoreactivity revealed that after RLN injury, GFAP immunoreactivity was increased beyond the area of the nucleus ambiguus within which RLN motor neuron somata were located. GFAP immunoreactivity was also observed in the vicinity of neuronal somata that project into the uninjured SLN. Similarly, lesion of the SLN resulted in increased GFAP immunoreactivity around the neuronal somata projecting into it and also in the vicinity of the motor neuron somata projecting into the RLN. The increase in GFAP immunoreactivity outside of the region containing the motor neurons projecting into the injured nerve, may reflect the onset of a regenerative process attempting to compensate for impairment of one of the laryngeal nerves and may occur because of the dual innervation of the posterior cricoarytenoid muscle. This dual innervation of a very specialised muscle could provide a useful model system for studying the molecular mechanisms underlying axonal regeneration process and the results of the current study could provide the basis for studies into functional regeneration

  6. 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

  7. Morphology of motoneurons in different subdivisions of the rat facial nucleus stained intracellularly with horseradish peroxidase.

    PubMed

    Friauf, E

    1986-11-08

    Horseradish peroxidase was injected into single facial motoneurons of the rat. Neurons were identified by antidromic stimulation of either the buccal or the marginal mandibular or the posterior auricular nerve branches. Motoneuronal cell bodies supplying the buccal branch were located in the lateral subdivision of the facial nucleus, those supplying the marginal mandibular branch were in the intermediate subdivision, and those supplying the posterior auricular branch were in the medial subdivision. Eleven motoneurons were reconstructed with a computer-assisted technique. Their soma diameters averaged 20 microns; the average number of primary dendrites was 7.9 and the combined lengths of the dendritic trees averaged 17,650 microns. There was no distinction between the three motoneuron groups in terms of these and other quantitative data. However, on the basis of reconstructed dendritic tree orientation (i.e., dendritic distribution), major differences were observed between motoneurons of the three groups. Dendrites from all groups extended beyond the boundaries of the facial nucleus into the reticular formation. The border between the intermediate and the lateral subdivision was crossed by some dendrites but the overlap was small. In contrast, no dendrite of a motoneuron in the medial subdivision entered the intermediate subdivision and vice versa. The dendritic extent was totally restricted by the borders between these two subdivisions. Outside the Nissl-defined nuclear border, however, dendrites from cells in adjacent subdivisions overlapped. It is concluded that the medial subdivision of the facial nucleus can be distinguished from the intermediate and lateral subdivisions not only by its sharp Nissl-defined border but also by the discrete organization of its dendritic field.

  8. Effect of motilin on gastric distension sensitive neurons in arcuate nucleus and gastric motility in rat.

    PubMed

    Xu, L; Gao, S; Guo, F; Sun, X

    2011-03-01

    Intestinal motilin is known to stimulate gastrointestinal (GI) motility and the arcuate nucleus (Arc) of hypothalamus is shown to be involved in the regulation of GI motility. Single unit discharges in the Arc were recorded extracellularly by implantation of a force transducer into the stomach in rats, to evaluate the effect of motilin on gastric motility. Projection of nerve fiber and expression of motilin were observed by retrograde tracer deposits of Fluoro-Gold (FG) and fluo-immunohistochemistry staining. 65.5% of neurons in Arc responded to gastric distension (GD), 55.6% of which showed excitation (GD-E), and 44.4% showed inhibition (GD-I). After GD, the firing rate of GD-E neurons significantly increased (P<0.01), but decreased for GD-I neurons (P<0.01). Most of both GD-E and GD-I neurons were activated by motilin (P<0.05). The frequency and amplitude of gastric contractions significantly increased by administration of motilin in Arc with a dose dependent manner (P<0.05-0.01). However, pretreatment with GM109 could abolish the responses of neurons and excitatory effect of gastric motility induced by motilin. Motilin immunoreactive neurons were increased in Arc via gastric distention (P<0.05). Motilin/FG-labeled neurons were detected in hypothalamus paraventricular nucleus (PVN). Our findings suggest that motilin neurons in Arc may accept peripheral somatosensory afferent inputs from gastric mechanoreceptors of the stomach, and also may acts as a stimulatory factor in Arc to regulate gastric motility via some inferior nucleus relay pathway. The results provide insight into the role of Arc in the control of digestion mediated via motilin. © 2011 Blackwell Publishing Ltd.

  9. Partial anxiolytic action of morphine sulphate following microinjection into the central nucleus of the amygdala in rats.

    PubMed

    File, S E; Rodgers, R J

    1979-09-01

    In the social interaction test of anxiety, bilateral microinjections of morphine sulphate (10 microgram) into the central nucleus of the amygdala counteracted the reduction in social interaction normally seen when the test arena is unfamiliar to rats. However, these injections did not counteract the decrease in social interaction that is observed as illuminance of the arena is increased. Morphine injections into the medial site depressed social interaction below the levels shown by control animals. In the open field test, morphine produced a facilitation of peripheral activity when injected into the central nucleus whilst a decrease in rearing was observed following similar injections into the medial nucleus. Overall, these data indicate a partial anxiolytic action of morphine in the central amygdaloid nucleus. Results are discussed in relation to possible differences in opioid peptide innervation of these two amygdaloid nuclei.

  10. Effects of electrical stimulation of the dorsal raphe nucleus on local cerebral blood flow in the rat

    SciTech Connect

    Bonvento, G.; Lacombe, P.; Seylaz, J. )

    1989-06-01

    We have studied the effects of electrical stimulation of the dorsal raphe nucleus on local cerebral blood flow (LCBF), as assessed by the quantitative ({sup 14}C)-iodoantipyrine autoradiographic technique. Stimulation of the dorsal raphe nucleus in the alpha-chloralose anesthetized rat caused a significant decrease in LCBF, ranging from -13 to -26% in 24 brain structures out of 33 investigated. The most pronounced decreases (-23 to -26%) were observed in the accumbens, amygdaloid, interpeduncular nuclei and in the median raphe nucleus, limbic system relays. The decreases also concerned cortical regions and the extrapyramidal system. These results indicate that activation of ascending serotonergic system produces a vasoconstriction and that the dorsal raphe nucleus has a widespread modulatory influence on the cerebral circulation.

  11. Nitric oxide in the nucleus raphe magnus modulates cutaneous blood flow in rats during hypothermia.

    PubMed

    Arami, Masoumeh Kourosh; Zade, Javad Mirnajafi; Komaki, Alireza; Amiri, Mahmood; Mehrpooya, Sara; Jahanshahi, Ali; Jamei, Behnam

    2015-10-01

    Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus. To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia. Intra-NRM injection of SNP (exogenous NO donor, 0.1- 0.2 μl, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1- 0.2 μl, 2.3 nM) into the nucleus increased the blood flow. This effect of L-glutamate was reduced by prior intra NRM administration of NO synthase inhibitor N(G)-methyl-L-arginine or N(G)-nitro-L-arginine methyl ester (L-NAME, 0.1 µl, 100 nM). It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interact with excitatory amino acids in central skin blood flow regulation.

  12. Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats

    PubMed Central

    Lin, Linghan

    2017-01-01

    The functions of mesenchymal stem cells (MSCs) appear to decline with age due to cellular senescence, which could reduce the efficacy of MSCs-based therapies. Recently, MSCs have been identified in the nucleus pulposus, which offers great potential for intervertebral disc (IVD) repair. However, this potential might be affected by the senescence of nucleus pulposus MSCs (NPMSCs), but whether or not this exists remains unknown. The aim of this study was to investigate the age-related changes in NPMSCs. NPMSCs isolated from young (3-month-old) and old (14-month-old) Sprague-Dawley rats were cultured in vitro. Differences in morphology, proliferation, colony formation, multilineage differentiation, cell cycle, and expression of β-galactosidase (SA-β-gal) and senescent markers (p53, p21, and p16) were compared between groups. Both young and old NPMSCs fulfilled the criteria for definition as MSCs. Moreover, young NPMSCs presented better proliferation, colony-forming, and multilineage differentiation capacities than old NPMSCs. Old NPMSCs displayed senescent features, including significantly increased G0/G1 phase arrest, increased SA-β-gal expression, decreased S phase entry, and significant p53-p21-pRB pathway activation. Therefore, this is the first study demonstrating that senescent NPMSCs accumulate in IVD with age. The efficacy of NPMSCs is compromised by donor age, which should be taken into consideration prior to clinical application. PMID:28396688

  13. Alertness opens the effective flow of sensory information through rat thalamic posterior nucleus.

    PubMed

    Sobolewski, Aleksander; Kublik, Ewa; Swiejkowski, Daniel A; Kamiński, Jan; Wróbel, Andrzej

    2015-05-01

    Behavioural reactions to sensory stimuli vary with the level of arousal, but little is known about the underlying reorganization of neuronal networks. In this study, we use chronic recordings from the somatosensory regions of the thalamus and cortex of behaving rats together with a novel analysis of functional connectivity to show that during low arousal tactile signals are transmitted via the ventral posteromedial thalamic nucleus (VPM), a first-order thalamic relay, to the primary somatosensory (barrel) cortex and then from the cortex to the posterior medial thalamic nucleus (PoM), which plays a role of a higher-order thalamic relay. By contrast, during high arousal this network scheme is modified and both VPM and PoM transmit peripheral input to the barrel cortex acting as first-order relays. We also show that in urethane anaesthesia PoM is largely excluded from the thalamo-cortical loop. We thus demonstrate a way in which the thalamo-cortical system, despite its fixed anatomy, is capable of dynamically reconfiguring the transmission route of a sensory signal in concert with the behavioural state of an animal.

  14. Nicotine withdrawal upregulates nitrergic and galaninergic activity in the rat dorsal raphe nucleus and locus coeruleus.

    PubMed

    Okere, Chuma O; Waterhouse, Barry D

    2013-03-01

    The dorsal raphe nucleus (DRN), a major source of forebrain serotonin, mediates various neural functions including anxiety. The nucleus locus coeruleus (LC) is likewise involved in mediating central components of the stress response and anxiety. An anxiety-reducing effect is widely believed to underlie many cases of nicotine dependence. While much is known about nicotine-serotonin interactions, little is known about how nicotine engages the DRN non-serotonergic domain in specific physiological functions that influence organismal behavior. The aim of this study was to determine how chronic nicotine withdrawal influences neuronal nitric oxide (NO) synthase (nNOS) and galanin immunoreactivity in the DRN and LC of adult rats. Compared with saline, nicotine increased nicotinamide adenine dinucleotide phosphate diaphorase profiles within distinct DRN subregions and also enhanced intensity in nNOS and galanin cell bodies in the rostral DRN as well as galanin in the LC. Nicotine-induced nNOS/galanin staining of somata was abundant in the rostral ventromedial DRN. Galanin-positive terminals surrounded nNOS-containing cell bodies in the DRN lateral wing subregions. These observations suggest that the DRN NOS-galanin domain and galanin in the LC are engaged in the organism's neural adaptation to chronic nicotine exposure. Hence NO and galanin synthesized or released within the DRN and LC or at the respective target sites might regulate the whole animal behavioral response to nicotine exposure.

  15. Nitric oxide in the nucleus raphe magnus modulates cutaneous blood flow in rats during hypothermia

    PubMed Central

    Arami, Masoumeh Kourosh; zade, Javad Mirnajafi; Komaki, Alireza; Amiri, Mahmood; Mehrpooya, Sara; Jahanshahi, Ali; Jamei, Behnam

    2015-01-01

    Objective(s): Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus. Materials and Methods: To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia. Results: Intra-NRM injection of SNP (exogenous NO donor, 0.1- 0.2 μl, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1- 0.2 μl, 2.3 nM) into the nucleus increased the blood flow. This effect of L-glutamate was reduced by prior intra NRM administration of NO synthase inhibitor NG-methyl-L-arginine or NG-nitro-L-arginine methyl ester (L-NAME, 0.1 µl, 100 nM). Conclusion: It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interact with excitatory amino acids in central skin blood flow regulation. PMID:26730333

  16. Gene expression in the rat supraoptic nucleus induced by chronic hyperosmolality versus hyposmolality.

    PubMed

    Glasgow, E; Murase, T; Zhang, B; Verbalis, J G; Gainer, H

    2000-10-01

    Magnocellular neurons of the hypothalamo-neurohypophysial system play a fundamental role in the maintenance of body homeostasis by secreting vasopressin and oxytocin in response to systemic osmotic perturbations. During chronic hyperosmolality, vasopressin and oxytocin mRNA levels increase twofold, whereas, during chronic hyposmolality, these mRNA levels decrease to 10-20% of that of normoosmolar control animals. To determine what other genes respond to these osmotic perturbations, we have analyzed gene expression during chronic hyper- versus hyponatremia. Thirty-seven cDNA clones were isolated by differentially screening cDNA libraries that were generated from supraoptic nucleus tissue punches from hyper- or hyponatremic rats. Further analysis of 12 of these cDNAs by in situ hybridization histochemistry confirmed that they are osmotically regulated. These cDNAs represent a variety of functional classes and include cytochrome oxidase, tubulin, Na(+)-K(+)-ATPase, spectrin, PEP-19, calmodulin, GTPase, DnaJ-like, clathrin-associated, synaptic glycoprotein, regulator of GTPase stimulation, and gene for oligodendrocyte lineage-myelin basic proteins. This analysis therefore suggests that adaptation to chronic osmotic stress results in global changes in gene expression in the magnocellular neurons of the supraoptic nucleus.

  17. Adiponectin modulates excitability of rat paraventricular nucleus neurons by differential modulation of potassium currents.

    PubMed

    Hoyda, Ted D; Ferguson, Alastair V

    2010-07-01

    The adipocyte-derived hormone adiponectin acts at two seven-transmembrane domain receptors, adiponectin receptor 1 and adiponectin receptor 2, present in the paraventricular nucleus of the hypothalamus to regulate neuronal excitability and endocrine function. Adiponectin depolarizes rat parvocellular preautonomic neurons that secrete either thyrotropin releasing hormone or oxytocin and parvocellular neuroendocrine corticotropin releasing hormone neurons, leading to an increase in plasma adrenocorticotropin hormone concentrations while also hyperpolarizing a subgroup of neurons. In the present study, we investigate the ionic mechanisms responsible for these changes in excitability in parvocellular paraventricular nucleus neurons. Patch clamp recordings of currents elicited from slow voltage ramps and voltage steps indicate that adiponectin inhibits noninactivating delayed rectifier potassium current (I(K)) in a majority of neurons. This inhibition produced a broadening of the action potential in cells that depolarized in the presence of adiponectin. The depolarizing effects of adiponectin were abolished in cells pretreated with tetraethyl ammonium (0/15 cells depolarize). Slow voltage ramps performed during adiponectin-induced hyperpolarization indicate the activation of voltage-independent potassium current. These hyperpolarizing responses were abolished in the presence of glibenclamide [an ATP-sensitive potassium (K(ATP)) channel blocker] (0/12 cells hyperpolarize). The results presented in this study suggest that adiponectin controls neuronal excitability through the modulation of different potassium conductances, effects which contribute to changes in excitability and action potential profiles responsible for peptidergic release into the circulation.

  18. Physiological properties of periodontal mechanosensitive neurones in the posteromedial ventral nucleus of rat thalamus.

    PubMed

    Tabata, T; Yamaki, A; Takahashi, Y; Hayashi, H

    2002-09-01

    Unitary discharges of periodontal mechanosensitive (PM) neurones responding to mechanical tooth stimulation were recorded from the posteromedial ventral nucleus (VPM) of rat thalamus. PM neurones are distributed in the ventromedial area in the rostral two-thirds of the VPM nucleus. Maxillary and mandibular tooth-sensitive neurones are arranged in dorsoventral sequence. Of the PM neurones, 36% were slowly adapting to pressure applied to the tooth and 67% were rapidly adapting. The majority of PM units were sensitive to the contralateral incisor tooth. Response magnitudes of the slowly adapting neurones varied with stimulus direction and were directionally selective to mechanical tooth stimulation. The optimal stimulus direction was labiolingual or linguolabial. Rapidly adapting neurones were directionally non-selective to tooth stimulation. The threshold for mechanical stimulation was <0.05 N. Mean response latencies evoked by electrical stimulation of the peripheral receptive fields were 4.6 ms in the slowly adapting neurones and 5.8 ms in the rapidly adapting neurones.

  19. Topographic relationship between anteromedial thalamic nucleus neurons and their cortical terminal fields in the rat.

    PubMed

    Shibata, H; Kato, A

    1993-06-01

    The present study has examined the topographic relationship between cells in the anteromedial thalamic nucleus (AM) and their cortical terminal fields, with retrograde transport of Fluoro Gold in the rat. Projections to the frontal area 2 originate from the ventrolateral part of the AM and the entire interanteromedial nucleus (IAM). Projections to the anterior cingulate area originate from the peripheral part of the rostral AM and the entire IAM. Fibers to the rostral retrosplenial area arise from the caudodorsal part of the AM, whereas those to the caudal retrosplenial area arise from the rostralmost and the rostrodorsomedial parts. Fibers to the rostral area 29D originate from the rostrocentral part of the AM, whereas those to the caudal area 29D originate from the rostroventrolateral and the ventromedial parts. Projections to the medial half of the entorhinal area originate from the rostrodorsomedial part of the AM. In contrast, projections to the lateral half of the entorhinal area originate from the IAM and the central part of the AM. The results show a complex topographic relationship between cells of origin of the AM and their cortical terminal fields, suggesting complex functional roles played by the AM in learning behavior such as discriminative avoidance behavior.

  20. In vivo monitoring of evoked noradrenaline release in the rat anteroventral thalamic nucleus by continuous amperometry.

    PubMed

    Dugast, C; Cespuglio, R; Suaud-Chagny, M F

    2002-08-01

    Continuous amperometry coupled with untreated carbon-fibre electrodes was used in anaesthetized rats to measure the noradrenaline release evoked in the anteroventral thalamic nucleus by electrical stimulation of the dorsal noradrenergic bundle. As expected, the variations in the oxidation current detected in the anteroventral thalamic nucleus exhibited the characteristics of the in vivo noradrenaline release. They were closely correlated with stimulation and consistent with the anatomy of the noradrenergic system involved. They were abolished by the ejection of tetrodotoxin in the vicinity of the carbon-fibre electrode, diminished by clonidine, an alpha-2 agonist, and restored by yohimbine, an alpha-2 antagonist. Furthermore, the time course of these variations was dramatically increased by desipramine, a specific noradrenaline reuptake blocker. In contrast, neither dopamine nor serotonin reuptake blockers, nor the monoamine oxidase inhibitor pargyline were able to alter them. The main advantage of the present approach is its excellent time resolution. We show here for the first time that after single pulse stimulation, noradrenaline is released and eliminated in 118 milliseconds, this time lapse corresponding to the maximal period beyond which subsequent noradrenaline releases could not add up. These observations are in good agreement with the physiological relationship previously observed between impulse flow and noradrenaline overflow.

  1. Phasic dopamine release in the rat nucleus accumbens predicts approach and avoidance performance

    PubMed Central

    Gentry, Ronny N.; Lee, Brian; Roesch, Matthew R.

    2016-01-01

    Dopamine (DA) is critical for reward processing, but significantly less is known about its role in punishment avoidance. Using a combined approach-avoidance task, we measured phasic DA release in the nucleus accumbens (NAc) of rats during presentation of cues that predicted reward, punishment or neutral outcomes and investigated individual differences based on avoidance performance. Here we show that DA release within a single microenvironment is higher for reward and avoidance cues compared with neutral cues and positively correlated with poor avoidance behaviour. We found that DA release delineates trial-type during sessions with good avoidance but is non-selective during poor avoidance, with high release correlating with poor performance. These data demonstrate that phasic DA is released during cued approach and avoidance within the same microenvironment and abnormal processing of value signals is correlated with poor performance. PMID:27786172

  2. Phasic dopamine release in the rat nucleus accumbens predicts approach and avoidance performance.

    PubMed

    Gentry, Ronny N; Lee, Brian; Roesch, Matthew R

    2016-10-27

    Dopamine (DA) is critical for reward processing, but significantly less is known about its role in punishment avoidance. Using a combined approach-avoidance task, we measured phasic DA release in the nucleus accumbens (NAc) of rats during presentation of cues that predicted reward, punishment or neutral outcomes and investigated individual differences based on avoidance performance. Here we show that DA release within a single microenvironment is higher for reward and avoidance cues compared with neutral cues and positively correlated with poor avoidance behaviour. We found that DA release delineates trial-type during sessions with good avoidance but is non-selective during poor avoidance, with high release correlating with poor performance. These data demonstrate that phasic DA is released during cued approach and avoidance within the same microenvironment and abnormal processing of value signals is correlated with poor performance.

  3. Taurine regulates corticotropin secretion at the level of the supraoptic nucleus during stress in rats.

    PubMed

    Engelmann, Mario; Landgraf, Rainer; Wotjak, Carsten T

    2003-09-11

    We studied the consequence of taurine release within the supraoptic nucleus (SON) for the hormonal stress response. Rats were chronically implanted with both microdialysis probes in the SON and jugular venous catheters. Three days later the animals received either Ringer's solution or a specific taurine antagonist via retrodialysis directly into the SON during a 10-min forced swimming session, while simultaneously blood samples were collected. Compared to the Ringer's control, treatment with the taurine antagonist significantly attenuated the increase in plasma corticotropin concentration caused by the stressor exposure (P < 0.05, analysis of variance). This finding supports the hypothesis that the hypothalamic-neurohypophysial system is a potent regulator of the hormonal stress response and suggests an important role for taurine in this context.

  4. Interactions between tactile and noxious visceral inputs in rat nucleus gracilus.

    PubMed

    Rong, Pei-Jing; Zhang, Jian-Liang; Zhang, Hong-Qi

    2004-05-20

    Recent studies have revealed that noxious visceral inputs travel in the dorsal column pathway, and interactions between colorectal noxious and tactile inputs occur in the ventrobasal thalamus. This investigation was to test whether the somatovisceral interactions also take place at a lower level in the dorsal column nuclei. Extracellular single neuron recordings were carried out in nucleus gracilus of anesthetized rats. Forty-three neurons responsive to colorectal distension (CRD) all had excitatory responses to tactile stimuli, and their tactile responses were predominantly (31/43 units) enhanced by preceding CRD. In contrast, the neuronal responses to CRD were reduced in 22/43 units when preceded by tactile stimulation but in two units there was an enhancement. The similarity and differences in the gracile response features in comparison with the thalamic recordings suggest that somatovisceral interactions take place at multiple levels in the dorsal column-medial lemniscus system.

  5. Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats.

    PubMed

    Murillo-Rodríguez, Eric; Haro, Reyes; Palomero-Rivero, Marcela; Millán-Aldaco, Diana; Drucker-Colín, René

    2007-01-25

    Modafinil (MOD) is a wakefulness-promoting drug that improves the alertness levels in narcolepsy; however, the molecular mechanism of action remains to be elucidated. We found that after a single icv injection of MOD (10 microg/5 microl) the extracellular levels of dopamine (DA) and l-DOPA collected from the nucleus accumbens were increased and decreased, respectively. Separately, the icv administration of MOD (10 microg/5 microl) to rats enhanced wakefulness (W) whereas diminished sleep during 4h. Lastly, the alertness induced by MOD was partially antagonized by the sleep-inducing endocannabinoid anandamide (ANA). We conclude that MOD enhances the extracellular levels of DA, promotes W and its effects on sleep are partially blocked by ANA.

  6. Female's DHT controls sex differences in the rat bed nucleus of the accessory olfactory tract.

    PubMed

    Collado, P; Segovia, S; Calés, J M; Pérez Laso, C; Rodriquez Zafra, M; Guillamón, A; Valencia, A

    1992-04-01

    In the present study the regulatory action of the non-aromatic androgen dihydrotestoterone (DHT) on the volume of the sexually dimorphic bed nucleus of the accessory olfactory tract (BAOT) was investigated. Postnatal treatment with DHT (180 micrograms day-1) between days 6 and 20 (D6-D20) induced, in gonadally intact male rats, a drastic reduction in the overall volume to levels typical in control females. Conversely, the postnatal administration of the anti-androgen cyproterone acetate (CA) to the females from D6-D20 produced an increment in the BAOT volume not dissimilar to that found in control males. These findings reveal that sexual organization in this vomeronasal structure is dependent on the presence of DHT in females during postnatal development.

  7. Food entrains clock genes but not metabolic genes in the liver of suprachiasmatic nucleus lesioned rats.

    PubMed

    Sabath, Elizabeth; Salgado-Delgado, Roberto; Guerrero-Vargas, Natali N; Guzman-Ruiz, Mara A; del Carmen Basualdo, Maria; Escobar, Carolina; Buijs, Ruud M

    2014-08-25

    Hepatic circadian transcription, considered to be driven by the liver clock, is largely influenced by food even uncoupling it from the suprachiasmatic nucleus (SCN). In SCN lesioned rats (SCNx) we determined the influence of a physiological feeding schedule on the entrainment of clock and clock-controlled (CCG) genes in the liver. We show that clock genes and the CCG Rev-erbα and peroxisome proliferator-activated receptor alpha (PPARα) in food-scheduled intact and SCNx have a robust diurnal differential expression persisting after a 24h fast. However, hepatic nicotinamide phosphoribosyl transferase (Nampt) shows time dependent changes that are lost in intact animals under fasting; moreover, it is unresponsive to the nutrient status in SCNx, indicating a poor reliance on liver clock genes and highlighting the relevance of SCN-derived signals for its metabolic status-related expression. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat.

    PubMed

    Yang, Jun; Chen, Jian-Min; Liu, Wen-Yan; Song, Cao-You; Wang, Cheng-Hai; Lin, Bao-Cheng

    2006-09-01

    Previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the NRM. The data suggest that AVP in the NRM is involved in antinociception.

  9. Distinct effect of orphanin FQ in nucleus raphe magnus and nucleus reticularis gigantocellularis on the rat tail flick reflex.

    PubMed

    Yang, Z; Zhang, Y; Wu, G

    2001-06-22

    The aim of the present study is to investigate the effects of orphanin FQ (OFQ) microinjected into the nucleus raphe magnus (NRM) and the nucleus reticularis gigantocellularis (NGC) on pain modulation. The tail-flick latency (TFL) was used as a behavioral index of nociceptive responsiveness. The result showed microinjection of OFQ into the NRM significantly increased the TFL, whereas microinjection of OFQ into the NGC decreased the TFL, suggesting the analgesic effect of OFQ in the NRM and the hyperalgesic effect of OFQ in the NGC. As there are three classes of putative pain modulating neurons in the rostral ventromedial medulla (RVM), the hyperalgesic or analgesic effect of OFQ in the RVM might depend upon the different class of the neurons being acted.

  10. Paleoamygdala: morphogenesis of the posterior cortical nucleus of the rat amygdaloid complex of the brain during the early juvenile period.

    PubMed

    Akhmadeev, A V; Kalimullina, L B

    2014-09-01

    Sex-related differences and the dynamic of formation of the posterior cortical nucleus of the rat amygdaloid complex were revealed in the early juvenile period by planimetric characteristics, numbers of neurons and glial cells, and glial and apoptotic indexes reflecting morphological restructuring on postnatal days 21, 24, 28, and 31.

  11. Rcan1 deficiency impairs neuronal migration and causes periventricular heterotopia.

    PubMed

    Li, Yang; Wang, Jie; Zhou, Yang; Li, Dan; Xiong, Zhi-Qi

    2015-01-14

    Periventricular heterotopia (PH) is a cortical malformation characterized by aggregation of neurons lining the lateral ventricles due to abnormal neuronal migration. The molecular mechanism underlying the pathogenesis of PH is unclear. Here we show that Regulators of calcineurin 1 (Rcan1), a Down syndrome-related gene, plays an important role in radial migration of rat cortical neurons. Downregulation of Rcan1 by expressing shRNA impaired neural progenitor proliferation and led to defects in radial migration and PH. Two isoforms of Rcan1 (Rcan1-1 and Rcan1-4) are expressed in the rat brain. Migration defects due to downregulation of Rcan1 could be prevented by shRNA-resistant expression of Rcan1-1 but not Rcan1-4. Furthermore, we found that Rcan1 knockdown significantly decreased the expression level of Flna, an F-actin cross-linking protein essential for cytoskeleton rearrangement and cell migration, mutation of which causes the most common form of bilateral PH in humans. Finally, overexpression of FLNA in Rcan1 knockdown neurons prevented migration abnormalities. Together, these findings demonstrate that Rcan1 acts upstream from Flna in regulating radial migration and suggest that impairment of Rcan1-Flna pathway may underlie PH pathogenesis.

  12. Erythropoietin-loaded oligochitosan nanoparticles for treatment of periventricular leukomalacia.

    PubMed

    Wang, Ting; Hu, Yan; Leach, Michelle K; Zhang, Long; Yang, Wenjing; Jiang, Li; Feng, Zhang-Qi; He, Nongyue

    2012-01-17

    In this study, a single intraperitoneal injection of erythropoietin (EPO) loaded oligochitosan nanoparticles (epo-NPs) (average diameter 266 nm) was investigated as a treatment for periventricular leukomalacia (PVL). Nanoparticles were fabricated using a gelation technology process. PVL rats models were prepared to examine the therapeutic efficacy of epo-NPs and analyze the mechanism by which epo-NPs protect white matter. The metabolization of epo-NPs in the liver was also investigated. The pathology and behavioral data show that this single injection of a low quantity of epo-NPs had an excellent therapeutic effect on the rat model of PVL. The EPO release curve in phosphate buffered saline solution was a good fit with the zero-order kinetics distribution and was maintained at around 25% in 48 h. In vivo experiments demonstrated that 50 IU/kg epo-NPs had the same effect as a 5000 IU/kg direct injection of free EPO. Nanoparticles prolonged the time course of EPO metabolization in the liver and the stable release of EPO from the nanoparticles kept the plasma concentration of EPO at around 100 IU/ml during the 8-12h post-injection. Therefore, we suggest that oligochitosan based nanoparticles are an effective vehicle for drug delivery.

  13. Upregulation of orexin receptor in paraventricular nucleus promotes sympathetic outflow in obese Zucker rats.

    PubMed

    Zhou, Jing-Jing; Yuan, Fang; Zhang, Yi; Li, De-Pei

    2015-12-01

    Sympathetic vasomotor tone is elevated in obesity-related hypertension. Orexin importantly regulates energy metabolism and autonomic function. We hypothesized that alteration of orexin receptor in the paraventricular nucleus (PVN) of the hypothalamus leads to elevated sympathetic vasomotor tone in obesity. We used in vivo measurement of sympathetic vasomotor tone and microinjection into brain nucleus, whole-cell patch clamp recording in brain slices, and immunocytochemical staining in obese Zucker rats (OZRs) and lean Zucker rats (LZRs). Microinjection of orexin 1 receptor (OX1R) antagonist SB334867 into the PVN reduced basal arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in anesthetized OZRs but not in LZRs. Microinjection of orexin A into the PVN produced greater increases in ABP and RSNA in OZRs than in LZRs. Western blot analysis revealed that OX1R expression levels in the PVN were significantly increased in OZRs compared with LZRs. OX1R immunoreactivity was positive in retrogradely labeled PVN-spinal neurons. The basal firing rate of labeled PVN-spinal neurons was higher in OZRs than in LZRs. SB334867 decreased the basal firing activity of PVN-spinal neurons in OZRs but had no effect in LZRs. Orexin A induced a greater increase in the firing rate of PVN-spinal neurons in OZRs than in LZRs. In addition, orexin A induced larger currents in PVN-spinal neurons in OZRs than in LZRs. These data suggest that upregulation of OX1R in the PVN promotes hyperactivity of PVN presympathetic neurons and elevated sympathetic outflow in obesity.

  14. N-methyl-norsalsolinol modulates serotonin metabolism in the rat caudate nucleus: correlation with behavioural changes.

    PubMed

    Thümen, Ansgar; Behnecke, Anne; Qadri, Fatimunnisa; Moser, Andreas

    2003-03-01

    In earlier studies the dihydroxylated tetrahydroisoquinoline derivative 2(N)-methyl-norsalsolinol (NMNorsal) was identified in patients with Parkinson's disease. In the present study, NMNorsal (20 or 40 mg/kg) was given intraperitoneally to rats kept under normal light-dark cycles. Using brain microdialysis technique, serotonin (5-HT), 5-hydroxyindolacetic acid (HIAA), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the dialysate from caudate nucleus in vivo and from tissue in vitro at various times following NMNorsal administration. Even after high-dose NMNorsal administration (40 mg/kg) and measurements up to 48 h after administration, levels of DA and its metabolite DOPAC were not modified. In contrast to the DA metabolism, 5-HT levels in the dialysate increased to approx. 2-fold during the 48 h following administration of a single high-dose of NMNorsal while HIAA decreased to approx. 50%. These changes of 5-HT and HIAA were nearly identical in the homogenate preparation of the caudate nucleus when compared to the amounts present in the dialysate. During assessment controls and low-dose-treated animals were almost always sleeping. Only high-dose NMNorsal-treated rats were active, with maximum activity after 48 h, however, behavioural activity was clearly different to the classical 5-HT behavioural syndrome. Taken together, increased 5-HT levels in the striatum found in our studies seem to be linked to the behavioural activity induced by high-dose NMNorsal, and NMNorsal appeared to perturb normal diurnal rhythms of spontaneous locomotor activity. The precise mechanism by which NMNorsal acts on 5-HT metabolism and behaviour is, however, unclear and further investigation is required.

  15. Dorsal Cochlear Nucleus of the Rat: Representation of Complex Sounds in Ears Damaged by Acoustic Trauma.

    PubMed

    Li, Yang; Ropp, Tessa-Jonne F; May, Bradford J; Young, Eric D

    2015-08-01

    Acoustic trauma damages the cochlea but secondarily modifies circuits of the central auditory system. Changes include decreases in inhibitory neurotransmitter systems, degeneration and rewiring of synaptic circuits, and changes in neural activity. Little is known about the consequences of these changes for the representation of complex sounds. Here, we show data from the dorsal cochlear nucleus (DCN) of rats with a moderate high-frequency hearing loss following acoustic trauma. Single-neuron recording was used to estimate the organization of neurons' receptive fields, the balance of inhibition and excitation, and the representation of the spectra of complex broadband stimuli. The complex stimuli had random spectral shapes (RSSs), and the responses were fit with a model that allows the quality of the representation and its degree of linearity to be estimated. Tone response maps of DCN neurons in rat are like those in other species investigated previously, suggesting the same general organization of this nucleus. Following acoustic trauma, abnormal response types appeared. These can be interpreted as reflecting degraded tuning in auditory nerve fibers plus loss of inhibitory inputs in DCN. Abnormal types are somewhat more prevalent at later times (103-376 days) following the exposure, but not significantly so. Inhibition became weaker in post-trauma neurons that retained inhibitory responses but also disappeared in many neurons. The quality of the representation of spectral shape, measured by sensitivity to the spectral shapes of RSS stimuli, was decreased following trauma; in fact, neurons with abnormal response types responded mainly to overall stimulus level, and not spectral shape.

  16. Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption.

    PubMed

    Bell, Richard L; Kimpel, Mark W; McClintick, Jeanette N; Strother, Wendy N; Carr, Lucinda G; Liang, Tiebing; Rodd, Zachary A; Mayfield, R Dayne; Edenberg, Howard J; McBride, William J

    2009-11-01

    The objective of this study was to determine the effects of binge-like alcohol drinking on gene expression changes in the nucleus accumbens (ACB) of alcohol-preferring (P) rats. Adult male P rats were given ethanol under multiple scheduled access (MSA; three 1-h dark cycle sessions/day) conditions for 8 weeks. For comparison purposes, a second ethanol drinking group was given continuous/daily alcohol access (CA; 24h/day). A third group was ethanol-naïve (W group). Average ethanol intakes for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hours after the last drinking episode, rats were euthanized, the brains extracted, and the ACB dissected. RNA was extracted and purified for microarray analysis. The only significant differences were between the CA and W groups (p<0.01; Storey false discovery rate=0.15); there were 374 differences in named genes between these 2 groups. There were 20 significant Gene Ontology (GO) categories, which included negative regulation of protein kinase activity, anti-apoptosis, and regulation of G-protein coupled receptor signaling. Ingenuity analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression in the ACB of the CA group), suggesting increased neuronal activity. There were 43 genes located within rat QTLs for alcohol consumption and preference; 4 of these genes (Tgfa, Hspa5, Mtus1 and Creb3l2) are involved in anti-apoptosis and increased transcription, suggesting that they may be contributing to cellular protection and maintaining high alcohol intakes. Overall, these findings suggest that chronic CA drinking results in genomic changes that can be observed during the early acute phase of ethanol withdrawal. Conversely, chronic MSA drinking, with its associated protracted withdrawal periods, results in genomic changes that may be masked by tight regulation of these genes following repeated experiences of ethanol withdrawal.

  17. Effects of Anterior Thalamic Nucleus Deep Brain Stimulation in Chronic Epileptic Rats

    PubMed Central

    Amorim, Beatriz; Cavarsan, Clarissa; Miranda, Maisa Ferreira; Aarão, Mayra C.; Madureira, Ana Paula; Rodrigues, Antônio M.; Nobrega, José N.; Mello, Luiz E.; Hamani, Clement

    2014-01-01

    Deep brain stimulation (DBS) has been investigated for the treatment of epilepsy. In rodents, an increase in the latency for the development of seizures and status epilepticus (SE) has been reported in different animal models but the consequences of delivering stimulation to chronic epileptic animals have not been extensively addressed. We study the effects of anterior thalamic nucleus (AN) stimulation at different current intensities in rats rendered epileptic following pilocarpine (Pilo) administration. Four months after Pilo-induced SE, chronic epileptic rats were bilaterally implanted with AN electrodes or had sham-surgery. Stimulation was delivered for 6 h/day, 5 days/week at 130 Hz, 90 µsec. and either 100 µA or 500 µA. The frequency of spontaneous recurrent seizures in animals receiving stimulation was compared to that recorded in the preoperative period and in rats given sham treatment. To investigate the effects of DBS on hippocampal excitability, brain slices from animals receiving AN DBS or sham surgery were studied with electrophysiology. We found that rats treated with AN DBS at 100 µA had a 52% non-significant reduction in the frequency of seizures as compared to sham-treated controls and 61% less seizures than at baseline. Animals given DBS at 500 µA had 5.1 times more seizures than controls and a 2.8 fold increase in seizure rate as compared to preoperative values. In non-stimulated controls, the average frequency of seizures before and after surgery remained unaltered. In vitro recordings have shown that slices from animals previously given DBS at 100 µA had a longer latency for the development of epileptiform activity, shorter and smaller DC shifts, and a smaller spike amplitude compared to non-stimulated controls. In contrast, a higher spike amplitude was recorded in slices from animals given AN DBS at 500 µA. PMID:24892420

  18. Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption

    PubMed Central

    Bell, Richard L.; Kimpel, Mark W.; McClintick, Jeanette N.; Strother, Wendy N.; Carr, Lucinda G.; Liang, Tiebing; Rodd, Zachary A.; Mayfield, R. Dayne; Edenberg, Howard J.; McBride, William J.

    2009-01-01

    The objective of this study was to determine the effects of binge-like alcohol drinking on gene expression changes in the nucleus accumbens (ACB) of alcohol-preferring (P) rats. Adult male P rats were given ethanol under multiple scheduled access (MSA; three 1-hr dark-cycle sessions/day) conditions for 8 weeks. For comparison purposes, a second ethanol drinking group was given continuous/daily alcohol access (CA; 24 hr/day). A third group was ethanol-naïve (W group). Average ethanol intakes for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last drinking episode, rats were euthanized, the brains extracted, and the ACB dissected. RNA was extracted and purified for microarray analysis. The only significant differences were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 differences in named genes between these 2 groups. There were 20 significant Gene Ontology (GO) categories, which included negative regulation of protein kinase activity, anti-apoptosis, and regulation of G-protein-coupled receptor signaling. Ingenuity® analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression in the ACB of the CA group), suggesting increased neuronal activity. There were 43 genes located within rat QTLs for alcohol consumption and preference; 4 of these genes (Tgfa, Hspa5, Mtus1 and Creb3l2) are involved in anti-apoptosis and increased transcription, suggesting that they may be contributing to cellular protection and maintaining high alcohol intakes. Overall, these findings suggest that chronic CA drinking results in genomic changes that can be observed during the early acute phase of ethanol withdrawal. Conversely, chronic MSA drinking, with its associated protracted withdrawal periods, results in genomic changes that may be masked by tight regulation of these genes following repeated experiences of ethanol withdrawal. PMID:19666046

  19. Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats.

    PubMed

    Laplante, François; Zhang, Zi-Wei; Huppé-Gourgues, Frédéric; Dufresne, Marc M; Vaucher, Elvire; Sullivan, Ron M

    2012-11-01

    In rats, selective depletion of the cholinergic interneurons in the ventral striatum (nucleus accumbens or N.Acc.) results in heightened behavioural sensitivity to amphetamine and impaired sensorimotor gating processes, suggesting a hyper-responsiveness to dopamine (DA) activity in the N.Acc. We hypothesized that local cholinergic depletion may also trigger distal functional alterations, particularly in prefrontal cortex (PFC). Adult male Sprague-Dawley rats were injected bilaterally in the N.Acc. with an immunotoxin targeting choline acetyltransferase. Two weeks later, cognitive function was assessed using the delayed alternation paradigm in the T-maze. The rats were then implanted with voltammetric recording electrodes in the ventromedial PFC to measure in vivo extracellular DA release in response to mild tail pinch stress. The PFC was also examined for density of tyrosine hydroxylase (TH)-labelled varicosities. In another cohort of control and lesioned rats, we measured post mortem tissue content of DA. Depletion of cholinergic neurons (restricted to N.Acc.) significantly impaired delayed alternation performance across delay intervals. While (basal) post mortem indices of PFC DA function were unaffected by N.Acc. lesions, in vivo mesocortical DA activation was markedly reduced; this deficit correlated significantly with cognitive impairments. TH-labelled varicosities however, were unaffected in cortical layer V relative to controls. These data suggest that selective depletion of cholinergic interneurons in N.Acc. triggers widespread functional impairments in mesocorticolimbic DA function and cognition. The possible relevance of these findings is also discussed in relation to schizophrenia, where reduced density of cholinergic neurons in ventral striatum has been reported. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Chronic Blockade of Phosphatidylinositol 3-Kinase in the Nucleus Tractus Solitarii Is Prohypertensive in the Spontaneously Hypertensive Rat

    PubMed Central

    Zubcevic, Jasenka; Waki, Hidefumi; Diez-Freire, Carlos; Gampel, Alexandra; Raizada, Mohan K.; Paton, Julian F.R.

    2009-01-01

    Phosphatidylinositol 3-kinase (PI3K) within brain stem neurons has been implicated in hypertension in the spontaneously hypertensive rat (SHR). Previously, we demonstrated elevated expression of PI3K subunits in rostral ventrolateral medulla and paraventricular nucleus of SHRs compared with Wistar-Kyoto rats. Here, we considered expression levels of PI3K in the nucleus tractus solitarii, a pivotal region in reflex regulation of arterial pressure, and determined its functional role for arterial pressure homeostasis in SHRs and Wistar-Kyoto rats. We found elevated mRNA levels of p110β and p110δ catalytic PI3K subunits in the nucleus tractus solitarii of adult (12 to 14 weeks old) SHRs relative to the age-matched Wistar-Kyoto rats (fold differences relative to β-actin: 1.7±0.2 versus 1.01±0.08 for p110β, n=6, P<0.05; 1.62±0.15 versus 1.02±0.1 for p110δ, n=6, P<0.05). After chronic blockade of PI3K signaling in the nucleus tractus solitarii by lentiviral-mediated expression of a mutant form of p85α, systolic pressure increased from 175±3 mm Hg to 191±6 mm Hg (P<0.01) in SHRs but not in Wistar-Kyoto rats. In addition, heart rate increased (from 331±6 to 342±6 bpm; P<0.05) and spontaneous baroreflex gain decreased (from 0.7±0.07 to 0.5±0.04 ms/mm Hg; P<0.001) in the SHRs. Thus, PI3K signaling in the nucleus tractus solitarii of SHR restrains arterial pressure in this animal model of neurogenic hypertension. PMID:19015400

  1. Eyeblink Classical Conditioning and Interpositus Nucleus Activity Are Disrupted in Adult Rats Exposed to Ethanol as Neonates

    PubMed Central

    Green, John T.; Johnson, Timothy B.; Goodlett, Charles R.; Steinmetz, Joseph E.

    2002-01-01

    Neonatal exposure to ethanol in rats, during the period of brain development comparable to that of the human third trimester, produces significant, dose-dependent cell loss in the cerebellum and deficits in coordinated motor performance. These rats are also impaired in eyeblink conditioning as weanlings and as adults. The current study examined single-unit neural activity in the interpositus nucleus of the cerebellum in adults following neonatal binge ethanol exposure. Group Ethanol received alcohol doses of 5.25 g/kg/day on postnatal days 4–9. Group Sham Intubated underwent acute intragastric intubation on postnatal days 4–9 but did not receive any infusions. Group Unintubated Control (from separate litters) did not receive any intubations. When rats were 3–7 mo old, pairs of extracellular microelectrodes were implanted in the region of the interpositus nucleus. Beginning 1 wk later, the rats were given either 100 paired or 190 unpaired trials per day for 10 d followed by 4 d of 100 conditioned stimulus (CS)-alone trials per day. As in our previous study, conditioned response acquisition in Group Ethanol rats was impaired. In addition, by session 5 of paired acquisition, Group Sham Intubated and Group Unintubated Control showed significant increases in interpositus nucleus activity, relative to baseline, in the CS–unconditioned stimulus interval. In contrast, Group Ethanol failed to show significant changes in interpositus nucleus activity until later in training. These results indicate that the disruption in eyeblink conditioning after early exposure to ethanol is reflected in alterations in interpositus nucleus activity. PMID:12359839

  2. Sulfated cholecystokinin-8 activates phospho-mTOR immunoreactive neurons of the paraventricular nucleus in rats

    PubMed Central

    Frommelt, Lisa; Inhoff, Tobias; Lommel, Reinhardt; Stengel, Andreas; Taché, Yvette; Grötzinger, Carsten; Bannert, Norbert; Wiedenmann, Bertram; Klapp, Burghard F.; Kobelt, Peter

    2014-01-01

    The serin/threonin-kinase, mammalian target of rapamycin (mTOR) was detected in the arcuate nucleus (ARC) and paraventricular nucleus of the hypothalamus (PVN) and suggested to play a role in the integration of satiety signals. Since cholecystokinin (CCK) plays a role in the short-term inhibition of food intake and induces c-Fos in PVN neurons, the aim was to determine whether intraperitoneally injected CCK-8S affects the neuronal activity in cells immunoreactive for phospho-mTOR in the PVN. Ad libitum fed male Sprague-Dawley rats received 6 or 10 μg/kg CCK-8S or 0.15 M NaCl ip (n=4/group). The number of c-Fosimmunoreactive (ir) neurons was assessed in the PVN, ARC and in the nucleus of the solitary tract (NTS). CCK-8S increased the number of c-Fos-ir neurons in the PVN (6 μg: 103 ± 13 vs. 10 μg: 165 ± 14 neurons/section; p<0.05) compared to vehicle treated rats (4 ± 1, p<0.05), but not in the ARC. CCK-8S also dose-dependently increased the number of c-Fos neurons in the NTS. Staining for phospho-mTOR and c-Fos in the PVN showed a dose-dependent increase of activated phospho-mTOR neurons (17 ± 3 vs. 38 ± 2 neurons/section; p<0.05), while no activated phospho-mTOR neurons were observed in the vehicle group. Triple staining in the PVN showed activation of phospho-mTOR neurons co-localized with oxytocin, corresponding to 9.8 ± 3.6% and 19.5 ± 3.3% of oxytocin neurons respectively. Our observations indicate that peripheral CCK-8S activates phospho-mTOR neurons in the PVN and suggest that phospho-mTOR plays a role in the mediation of CCK-8S's anorexigenic effects. PMID:20933028

  3. Participation of thalamic nuclei in the elaboration of conditioned avoidance reflexes of rats. VIII. Lesions of the nucleus posterior.

    PubMed

    Klingberg, F; Klingberg, H

    1982-01-01

    Bilateral symmetric lesions of the posterior thalamic nucleus reduced the preoperatively learnt avoidance responses in Long-Evans hooded rats strongly. Postoperative acquisition of conditioned avoidance reflexes was rather low in each rat in a simple runway and impossible in an alternation task. Thresholds of reactions to pain (withdrawal of paws from the grid floor) were significantly increased. The lesioned rats had trouble to find the way out, as if they had difficulties to localize the source of punishment or to associate pain information with any other cues.

  4. [Changes in DNA repair enzymes in rat ventroposterior nucleus of the thalamus after cerebral cortex infarction].

    PubMed

    He, Mei-Xia; Zeng, Jin-Sheng; Hua, Hai-Ying; Xing, Shi-Hui; Ba, Yun-Peng

    2010-10-01

    To investigate the damage within the ventroposterior nucleus (VPN) of the thalamus after focal cortical infarction and its mechanism, and explore the effect of ebselen on the oxidative damage after cerebral cortex infarction in hypertensive rats. Middle cerebral artery occlusion (MCAO) was induced in stroke-prone renovascular hypertensive rats (RHRSP), and the rats were divided into four groups by table of random number: sham operation group, model group, vehicle group and ebselen group, each group consisted of 8 rats. In animals subjected to sham surgery the middle cerebral artery was exposed only. Ebselen (5 ml/kg) or vehicle (a mixed solvent consisting of 0.5% carboxymethyl cellulose and 0.02% Tween 20, 5 ml/kg) was given by gastric gavage starting 24 hours after cerebral cortical infarction. Two weeks after the MCAO, the rats were sacrificed, and VPN from each group was sectioned and stained with hematoxylin-eosin (HE), and apurinic/apyrimidinic endonuclease (APE) and Escherichia coli MutY DNA glycosylase (MYH) were determined by immunohistochemistry. HE staining showed that ebselen ameliorated the VPN damage induced by ischemia. Immunohistochemical imaging analysis revealed a distinct nuclear staining of APE and nuclear and cytoplasm distribution of MYH in the entire region of the VPN. Compared with sham operation group, the number of APE and MYH positive cells decreased in model group and vehicle group (APE: 57.0±14.7, 49.4±12.5 vs. 101.0±13.6, MYH: 15.0±4.7, 10.4±2.5 vs. 56.0±13.2, all P<0.05). Compared with model group and vehicle group, the number of APE and MYH positive cells increased significantly in ebselen group (APE: 72.2±7.6 vs. 57.0±14.7, 49.4±12.5, MYH: 32.2±7.6 vs. 15.0±4.7, 10.4±2.5, all P<0.05); the difference of the number of APE and MYH positive cells between model group and vehicle group showed no statistical significance. After 2 weeks of MCAO, there is a marked decrease of APE and MYH in VPN; ebselen can obviously increase the

  5. Lesion of the Subfornical Organ attenuates Neuronal Activation of the Paraventricular Nucleus in response to Angiotensin II in normal rats.

    PubMed

    Meehan, Jessica; Collister, John P

    2011-09-23

    The subfornical organ, one of the central circumventricular organs, has been shown to mediate many of the effects of circulating angiotensin II (AngII). Where these signals are processed downstream is not fully understood. The SFO does indeed project to prominent cardiovascular regulatory centers such as the paraventricular nucleus (PVN), of whose neurons are activated by central AngII. We reasoned that AngII sensed at the SFO would cause neuronal activation at downstream hypothalamic areas such as the median preoptic nucleus and paraventricular nucleus, and as such would be diminished in animals with lesions of the SFO. To test this hypothesis, groups of rats underwent either SFO lesion (SFOx) or sham operation. Five days later rats were instrumented with radiotelemetry transducers for monitoring of mean arterial pressure (MAP) and venous catheters for infusions. MAP and heart rate were measured continuously. After a 4 day control period, infusion of AngII (0.575 µg/kg/min) was begun for a period of 2 hours. Rats were then sacrificed and brains were processed for neuronal Fos expression. AngII produced Fos expression in the SFO, MnPO and PVN of sham rats. Fos expression was greatly attenuated in the PVN of SFOx rats. These results support our hypothesis, suggesting that AngII sensitive neurons of the SFO can mediate neuronal activation in the PVN.

  6. 'Hidden lamination' in the dorsal lateral geniculate nucleus: the functional organization of this thalamic region in the rat.

    PubMed

    Reese, B E

    1988-01-01

    The cyto-and myeloarchitecture of the rat's dorsal lateral geniculate nucleus (dLGN) display none of the laminar features characteristic of this thalamic region in carnivores and primates. Despite this, the rodent's nucleus contains a segregation of functionally and ocularly distinct afferents--organizational properties manifested in the prominent lamination of these other mammalian forms. The rat's dLGN can be divided into two main regions: an inner core and an outer shell. The inner core contains two ocular laminae receiving direct retinotopic projections from the contralateral nasal and ipsilateral temporal retinae, mapping the contralateral visual hemifield. The outer shell receives a retinotopic projection from the complete contralateral retina only, the representation of the ipsilateral hemifield being extremely compressed at the medial edge of this lamina. The retinotopic maps in these three ocular laminae (contra, ipsi, contra) are in conjugate register, so that lines of projection course rostro-ventro-medially from the optic tract at the thalamic surface through these laminae. Three morphologically distinct retinal ganglion cell types project to the dLGN, and the axons of these ganglion cells are partially segregated within the optic tract in anticipation of their segregation within the nucleus, where they terminate at distinct locations along the lines of projection. Type I and III cells terminate in the inner core of the nucleus, while type II and III cells terminate in the outer shell. The outer shell also receives a direct projection from the superior colliculus. These characteristics of the afferent termination within the rat's dLGN support the view of a general mammalian plan for the organization of this thalamic region, and provide a basis for further experimentation to test speculations about potentially homologous subdivisions of this nucleus. Conclusions regarding functionally analogous pathways are proposed with less confidence, due to the

  7. Maternal behavior induced in male rats by bilateral lesions of the bed nucleus of the accessory olfactory tract.

    PubMed

    Izquierdo, M A; Collado, P; Segovia, S; Guillamón, A; del Cerro, M C

    1992-10-01

    In the present study, we investigate the effect of bilateral electrolytic lesions of the bed nucleus of the accessory olfactory tract (BAOT) in male Wistar rats that did not have care-pups experience, using a test of induced maternal behavior. Consistent with our previous findings in virgin female rats (10), there was a significantly shorter sensitization (3 days) and retrieval (2 days) latencies in the BAOT-lesioned group than in the sham-lesioned and intact-control male groups (12 days for both). Based on these findings, we propose that BAOT, a sexually dimorphic nucleus of the vomeronasal system, exerts an inhibitory modulation in the expression of parental behavior in male and female virgin rats. It may do so by maintaining an olfactory-based tonic inhibition of maternal behavior, thereby resulting in the adults' tonic avoidance of the pups until this inhibition is abolished by lesion, or reduced or overridden by appropriate hormonal and/or sensory influences.

  8. Lateral habenula and the rostromedial tegmental nucleus innervate neurochemically distinct subdivisions of the dorsal raphe nucleus in the rat.

    PubMed

    Sego, Chemutai; Gonçalves, Luciano; Lima, Leandro; Furigo, Isadora C; Donato, Jose; Metzger, Martin

    2014-05-01

    The lateral habenula (LHb) is an epithalamic structure differentiated in a medial (LHbM) and a lateral division (LHbL). Together with the rostromedial tegmental nucleus (RMTg), the LHb has been implicated in the processing of aversive stimuli and inhibitory control of monoamine nuclei. The inhibitory LHb influence on midbrain dopamine neurons has been shown to be mainly mediated by the RMTg, a mostly GABAergic nucleus that receives a dominant input from the LHbL. Interestingly, the RMTg also projects to the dorsal raphe nucleus (DR), which also receives direct LHb projections. To compare the organization and transmitter phenotype of LHb projections to the DR, direct and indirect via the RMTg, we first placed injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the LHb or the RMTg. We then confirmed our findings by retrograde tracing and investigated a possible GABAergic phenotype of DR-projecting RMTg neurons by combining retrograde tracing with in situ hybridization for GAD67. We found only moderate direct LHb projections to the DR, which mainly emerged from the LHbM and were predominantly directed to the serotonin-rich caudal DR. In contrast, RMTg projections to the DR were more robust, emerged from RMTg neurons enriched in GAD67 mRNA, and were focally directed to a distinctive DR subdivision immunohistochemically characterized as poor in serotonin and enriched in presumptive glutamatergic neurons. Thus, besides its well-acknowledged role as a GABAergic control center for the ventral tegmental area (VTA)-nigra complex, our findings indicate that the RMTg is also a major GABAergic relay between the LHb and the DR.

  9. Lesions of the nucleus accumbens disrupt reinforcement omission effects in rats.

    PubMed

    Judice-Daher, Danielle M; Bueno, José Lino O

    2013-09-01

    The reinforcement omission effects (ROEs) have been attributed to both motivational and attentional consequences of the surprising reinforcement omission. Some studies have been showed amygdala is part of a circuit involved in the ROEs modulation. The view that amygdala lesions interfere with the ROEs is supported by evidence involving amygdala in responses correlated with motivational processes. These processes depend on the operation of separate amygdala areas and their connections with other brain systems. It has been suggested the interaction between the amygdala and the nucleus accumbens (NAC) is important to the modulation of motivational processes. Recent neuroimaging studies in human revealed reward delivery enhances activity of subcortical structures (NAC and amygdala), whereas reward omission reduces the activity in these same structures. The present study aimed to clarify whether the mechanisms related to ROEs depend on NAC. Prior to acquisition training, rats received bilateral excitotoxic lesions of NAC (NAC group) or sham lesions (Sham group). Following postoperative recovery, the rats were trained on a fixed-interval with limited hold signaled schedule of reinforcement. After acquisition of stable performance, the training was changed from 100% to 50% schedule of reinforcement. Both NAC and Sham groups presented the ROEs. However, after nonreinforcement, the response rates of the NAC group were lower than those registered in the Sham group. The performance of the NAC group decreased in the period following nonreinforcement when compared to the period preceding reinforcement omission. These findings suggest the NAC is part of the neural substrate involved in the ROEs modulation.

  10. Local salsolinol modulates dopamine extracellular levels from rat nucleus accumbens: shell/core differences.

    PubMed

    Hipólito, Lucía; Sánchez-Catalán, María José; Granero, Luis; Polache, Ana

    2009-09-01

    Salsolinol (SAL), a condensation product of dopamine and acetaldehyde that appears in the rat and human brain after ethanol ingestion, has been largely implicated in the aetiology of alcoholism. Although the behavioural consequences of systemic or intracerebral SAL administrations have been described, the neurochemical effects of pharmacologically relevant doses of SAL and other tetrahydroisoquinolines (THIQs) in the brain areas involved in alcohol addiction are practically unknown. To gain an insight into this topic, male Wistar rats were stereotaxically implanted with one concentric microdialysis probe in either the shell or the core of the nucleus accumbens (NAc). Treatments involved local administration of 0.1, 5 and 25 microM SAL for 20 min through the dialysis probe. Dopamine (DA) concentrations in the shell or core of the NAc were on-line analyzed every 20 min by HPLC with electrochemical detection. Implantation of the probe was histologically evaluated at the end of the experiments. Our results indicate that dialysis application of 5 and 25 microM SAL into the core increased the dialysate levels of DA. Conversely, the administration of the same doses of this drug into the shell significantly reduced the DA levels in this subregion. In conclusion, these data reveal that local application of SAL affects the DA levels in the NAc subterritories in a region-specific manner. These findings may prove useful in probing CNS sites and mechanisms involved in alcohol consumption.

  11. Lesion of the tuberomammillary nucleus E2-region attenuates postictal seizure protection in rats.

    PubMed

    Jin, Chun-Lei; Zhuge, Zheng-Bing; Wu, Deng-Chang; Zhu, Yuan-Yuan; Wang, Shuang; Luo, Jian-Hong; Chen, Zhong

    2007-03-01

    Postictal seizure protection (PSP) is an endogenous anticonvulsant phenomenon that follows an epileptic seizure and inhibits the induction of further seizures. The tuberomammillary nucleus (TM), located in the posterior hypothalamus, consists of five subregions and is the sole source of histaminergic neurons in the brain. To determine whether the TM is involved in PSP in rats, we tested the effects of bilateral electrolytic lesions of the TM E2-region on seizures induced by intermittent maximal electroshock (MES). The TM E2-region lesions significantly attenuated PSP during the intermittent MES procedure. Furthermore, intracerebroventricular injection of alpha-fluoromethylhistidine (100 microg), a selective and irreversible histidine decarboxylase inhibitor, mimicked the attenuation of PSP induced by the lesion of TM E2-region. In addition, neurochemical experiments revealed that the TM E2-region lesions markedly decreased basal histamine levels in the cortex, hippocampus, brainstem and hypothalamus, but had no significant effect on basal glutamate and GABA levels. Moreover, intermittent MES induced a persistent decrease of brain histamine levels in both sham-operated and lesioned rats. These results indicate that through its intrinsic histaminergic system, the TM may exert powerful inhibitory function during the intermittent MES procedure and actively participate in the mechanisms of PSP.

  12. Kisspeptin-10 potentiates miniature excitatory postsynaptic currents in the rat supraoptic nucleus.

    PubMed

    Yokoyama, Toru; Minami, Kouichiro; Terawaki, Kiyoshi; Miyano, Kanako; Ogata, Junichi; Maruyama, Takashi; Takeuchi, Mamoru; Uezono, Yasuhito; Ueta, Yoichi

    2014-10-02

    Kisspeptin is the natural ligand of the G protein-coupled receptor -54 and plays a major role in gonadotropin-releasing hormone secretion in the hypothalamus. Kisspeptin-10 is an endogenous derivative of kisspeptin and has 10 -amino acids. Previous studies have demonstrated that central administration of kisspeptin-10 stimulates the secretion of arginine vasopressin (AVP) in male rats. We examined the effects of kisspeptin-10 on- excitatory synaptic inputs to magnocellular neurosecretory cells (MNCs) including AVP neurons in the supraoptic nucleus (SON) by obtaining in vitro whole-cell patch-clamp recordings from slice preparations of the rat brain. The application of kisspeptin-10 (100 nM-1 μM) significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in a dose-related manner without affecting the amplitude. The kisspeptin-10-induced potentiation of the mEPSCs was significantly attenuated by previous exposure to the kisspeptin receptor antagonist kisspeptin-234 (100 nM) and to the protein kinase C inhibitor bisindolylmaleimide I (20 nM). These results suggest that kisspeptin-10 participates in the regulation of synaptic inputs to the MNCs in the SON by interacting with the kisspeptin receptor.

  13. Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain injury.

    PubMed

    Li, Yafei; Li, Xihong; Qu, Yi; Huang, Jichong; Zhu, Tingting; Zhao, Fengyan; Li, Shiping; Mu, Dezhi

    2017-04-03

    High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining. Cortical levels of HMGB1, its receptor for advanced glycation end-products (RAGE), and downstream effecter, nuclear factor kappa-B (NF-κB) subunit p65, were detected via western blot.HMGB1was increased in the cytoplasm via translocation from the nucleus predominantly in neurons. Moreover, RAGE and NF-κB p65 were upregulated after septic brain injury. Ethyl pyruvate, an inhibitor of HMGB1, down-regulated the expression of RAGE and NF-κB p65via inhibiting HMGB1 expression in the cytoplasm. Collectively, our findings suggest that HMGB1 and its signaling transduction have critical roles in the pathogenesis of septic brain injury. HMGB1 inhibition might be a potential new therapeutic target for septic brain injury.

  14. Positive reinforcing effects of RFamide-related peptide-1 in the rat central nucleus of amygdala.

    PubMed

    Lénárd, László; Kovács, Anita; Ollmann, Tamás; Péczely, László; Zagoracz, Olga; Gálosi, Rita; László, Kristóf

    2014-12-15

    The amygdaloid body (AMY) plays an important role in memory, learning and reward-related processes. RFamide-related peptide-1 (RFRP-1) immunoreactive fibers and NPFF1 receptors were identified in the AMY, and previously we verified that neuropeptide RFRP-1 infused into the central nucleus of AMY (CeA) caused food intake decrease. The aim of the present study was to examine the possible rewarding or aversive effects of RFRP-1 in the CeA. In conditioned place preference, test male Wistar rats were microinjected bilaterally with 50 or 100ng RFRP-1 in volume of 0.4μl. In other groups of animals, 20ng NPFF receptor antagonist RF9 was applied or the antagonist was used 15min before 50ng RFRP-1 treatment. Fifty nanograms of RFRP-1 had positive reinforcing properties, while 100ng RFRP-1 had no effect. Prior treatment with NPFF receptor antagonist RF9 could block the rewarding effects of RFRP-1, while the antagonist applied alone did not influence the behavior of rats in place preference paradigm. Our results show that RFRP-1 and NPFF-1 receptors play important roles in the amygdaloid rewarding-reinforcing mechanisms.

  15. The involvement of norepinephrine in pain modulation in the nucleus accumbens of morphine-dependent rats.

    PubMed

    Zhang, Ying; Qu, Hui; Zhou, You; Wang, Yi; Zhang, Duo; Yang, Xu; Yang, ChunXiao; Xu, ManYing

    2015-01-12

    Opioids are effective analgesics used clinically for both acute and chronic pain management. However, repeated opioid treatment can induce serious side effects such as nausea, vomiting, drowsiness, respiratory depression, euphoria, dependence, hyperalgesia, and tolerance. The mechanism of noxious information transmission in the central nervous system following dependence is still not clear. Norepinephrine (NE), an important neurotransmitter, participates both in the process of opioid dependence and also pain modulation in the central nervous system. In this study, we examined the role of NE on the evoked discharges of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the nucleus accumbens (NAc) of rats, following the development of morphine dependence. Our results revealed that NE inhibited the evoked discharges of PENs and attenuated the inhibition of PINs, while phentolamine enhanced the evoked discharges of PENs and facilitated the inhibition of PINs. These results indicate that the inhibitory action of NE on pain modulation acts via alpha adrenoceptors in the NAc of morphine-dependent rats.

  16. ANABOLIC-ANDROGENIC STEROIDS DECREASE DENDRITIC SPINE DENSITY IN THE NUCLEUS ACCUMBENS OF MALE RATS

    PubMed Central

    Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana; Wood, Ruth I.

    2016-01-01

    Recent studies have demonstrated that anabolic-androgenic steroids (AAS) modify cognitive processes such as decision making and behavioral flexibility. However, the neural mechanisms underlying these AAS-induced cognitive changes remain poorly understood. The mesocorticolimbic dopamine (DA) system, particularly the nucleus accumbens (Acb), is important for reward, motivated behavior, and higher cognitive processes such as decision making. Therefore, AAS-induced plasticity in the DA system is a potential structural substrate for the observed cognitive alterations. High doses of testosterone (the most commonly-used AAS) increase dendritic spine density in limbic regions including the amygdala and hippocampus. However, effects on Acb are unknown. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically for 8 weeks with high-dose testosterone (7.5 mg/kg in water with 13% cyclodextrin) or vehicle sc. Brains were stained by Golgi-Cox to analyze neuronal morphology in medium spiny neurons of the shell region of Acb (AcbSh). 8 weeks of testosterone treatment significantly decreased spine density in AcbSh compared to brains of vehicle-treated rats (F1,14 = 5.455, p<0.05). Testosterone did not significantly affect total spine number, dendritic length, or arborization measured by Sholl analysis. These results show that AAS alter neuronal morphology in AcbSh by decreasing spine density throughout the dendritic tree, and provides a potential mechanism for AAS to modify cognition and decision-making behavior. PMID:27238893

  17. The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

    PubMed Central

    Baldi, Elisabetta; Mariottini, Chiara; Bucherelli, Corrado

    2007-01-01

    The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear training to acoustic conditioned stimulus (CS) and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as the conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way, there was no interference with normal NBM function during either acquisition or retrieval phases, allowing any amnesic effect to be due only to consolidation disruption. The results show that for contextual fear response memory consolidation, NBM functional integrity is necessary up to 24 h post-acquisition. On the other hand, NBM functional integrity was shown to be necessary for memory consolidation of the acoustic CS fear response only immediately after acquisition and not 24-h post-acquisition. The present findings help to elucidate the role of the NBM in memory consolidation and better define the neural circuits involved in fear memories. PMID:18086829

  18. Inner capillary diameter of hypothalamic paraventricular nucleus of female rat increases during lactation

    PubMed Central

    2013-01-01

    Background The role of the endothelial cell (EC) in blood flow regulation within the central nervous system has been little studied. Here, we explored EC participation in morphological changes of the anterior hypothalamic paraventricular nucleus (PVN) microvasculature of female rats at two reproductive stages with different metabolic demand (virginity and lactation). We measured the inner capillary diameter (ICD) of 800 capillaries from either the magnocellular or parvocellular regions. The space occupied by neural (somas, dendrites and axons) and glial, but excluding vascular elements of the neurovascular compartment was also measured in 100-μm2 sample fields of both PVN subdivisions. Results The PVN of both groups of animals showed ICDs that ranged from 3 to 10 microns. The virgin group presented mostly capillaries with small ICD, whereas the lactating females exhibited a significant increment in the percentage of capillaries with larger ICD. The space occupied by the neural and glial elements of the neurovascular compartment did not show changes with lactation. Conclusions Our findings suggest that during lactation the microvasculature of the PVN of female rats undergoes dynamic, transitory changes in blood flow as represented by an increment in the ICD through a self-cytoplasmic volume modification reflected by EC changes. A model of this process is proposed. PMID:23302443

  19. Intrinsic properties of the sodium sensor neurons in the rat median preoptic nucleus

    PubMed Central

    Voisin, Aurore N.; Mouginot, Didier

    2012-01-01

    The essential role of the median preoptic nucleus (MnPO) in the integration of chemosensory information associated with the hydromineral state of the rat relies on the presence of a unique population of sodium (Na+) sensor neurons. Little is known about the intrinsic properties of these neurons; therefore, we used whole cell recordings in acute brain slices to determine the electrical fingerprints of this specific neural population of rat MnPO. The data collected from a large sample of neurons (115) indicated that the Na+ sensor neurons represent a majority of the MnPO neurons in situ (83%). These neurons displayed great diversity in both firing patterns induced by transient depolarizing current steps and rectifying properties activated by hyperpolarizing current steps. This diversity of electrical properties was also present in non-Na+ sensor neurons. Subpopulations of Na+ sensor neurons could be distinguished, however, from the non-Na+ sensor neurons. The firing frequency was higher in Na+ sensor neurons, showing irregular spike discharges, and the amplitude of the time-dependent rectification was weaker in the Na+ sensor neurons than in non-Na+ sensor neurons. The diversity among the electrical properties of the MnPO neurons contrasts with the relative function homogeneity (Na+ sensing). However, this diversity might be correlated with a variety of direct synaptic connections linking the MnPO to different brain areas involved in various aspects of the restoration and conservation of the body fluid homeostasis. PMID:22874426

  20. The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat.

    PubMed

    Baldi, Elisabetta; Mariottini, Chiara; Bucherelli, Corrado

    2007-12-01

    The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear training to acoustic conditioned stimulus (CS) and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as the conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way, there was no interference with normal NBM function during either acquisition or retrieval phases, allowing any amnesic effect to be due only to consolidation disruption. The results show that for contextual fear response memory consolidation, NBM functional integrity is necessary up to 24 h post-acquisition. On the other hand, NBM functional integrity was shown to be necessary for memory consolidation of the acoustic CS fear response only immediately after acquisition and not 24-h post-acquisition. The present findings help to elucidate the role of the NBM in memory consolidation and better define the neural circuits involved in fear memories.

  1. Lesions of the rat nucleus basalis magnocellularis disrupt appetitive-to-aversive transfer learning.

    PubMed

    Butt, A E; Schultz, J A; Arnold, L L; Garman, E E; George, C L; Garraghty, P E

    2003-01-01

    Rats with selective lesions of the nucleus basalis magnocellularis (NBM) and sham-lesion control animals were tested in an operant appetitive-to-aversive transfer task. We hypothesized that NBM lesions would not affect performance in the appetitive phase, but that performance would be impaired during subsequent transfer to the aversive phase of the task. Additional groups of NBM lesion and control rats were tested in the avoidance condition only, where we hypothesized that NBM lesions would not disrupt performance. These hypotheses were based on the argument that the NBM is not necessary for simple association learning that does not tax attention. Both the appetitive phase of the transfer task and the avoidance only task depend only on simple associative learning and are argued not to tax attention. Consequently, performance in these tasks was predicted to be spared following NBM lesions. Complex, attention-demanding associative learning, however, is argued to depend on the NBM. Performance in the aversive phase of the transfer task is both attentionally demanding and associatively more complex than in either the appetitive or aversive tasks alone; thus, avoidance performance in the NBM lesion group was predicted to be impaired following transfer from prior appetitive conditioning. Results supported our hypotheses, with the NBM lesion group acquiring the appetitive response normally, but showing impaired performance following transfer to the aversive conditioning phase of the transfer task. Impairments were not attributable to disrupted avoidance learning per se, as avoidance behavior was normal in the NBM lesion group tested in the avoidance condition only.

  2. Role of the trigeminal mesencephalic nucleus in rat whisker pad proprioception

    PubMed Central

    2010-01-01

    Background Trigeminal proprioception related to rodent macrovibrissae movements is believed to involve skin receptors on the whisker pad because pad muscles operate without muscle spindles. This study was aimed to investigate in rats whether the trigeminal mesencephalic nucleus (TMnu), which provides proprioceptive feedback for chewing muscles, may be also involved in whisker pad proprioception. Methods Two retrograde tracers, Dil and True Blue Chloride, were injected into the mystacial pad and the masseter muscle on the same side of deeply anesthetized rats to label the respective projecting sensory neurons. This double-labeling technique was used to assess the co-innervation of both structures by the trigeminal mesencephalic nucleus (TMnu). In a separate group of anesthetized animals, the spontaneous electrical activities of TMnu neurons were analyzed by extracellular recordings during spontaneous movements of the macrovibrissae. Mesencephalic neurons (TMne) were previously identified by their responses to masseter muscle stretching. Changes in TMne spontaneous electrical activities, analyzed under baseline conditions and during whisking movements, were statistically evaluated using Student's t-test for paired observations. Results Neuroanatomical experiments revealed different subpopulations of trigeminal mesencephalic neurons: i) those innervating the neuromuscular spindles of the masseter muscle, ii) those innervating the mystacial pad, and iii) those innervating both structures. Extracellular recordings made during spontaneous movements of the macrovibrisae showed that whisking neurons similar to those observed in the trigeminal ganglion were located in the TMnu. These neurons had different patterns of activation, which were dependent on the type of spontaneous macrovibrissae movement. In particular, their spiking activity tonically increased during fan-like movements of the vibrissae and showed phasic bursting during rhythmic whisking. Furthermore, the same

  3. The effect of repetitive transcranial magnetic stimulation on monoamine outflow in the nucleus accumbens shell in freely moving rats.

    PubMed

    Löffler, Susanne; Gasca, Fernando; Richter, Lars; Leipscher, Ulrike; Trillenberg, Peter; Moser, Andreas

    2012-10-01

    Evidence exists that modulation of neuronal activity in nucleus accumbens shell region may re-establish normal function in various neuropsychiatric conditions such as drug-withdrawal, obsessive-compulsive disorder, depression and chronic pain. Here, we study the effects of acute repetitive transcranial magnetic stimulation on monoamine outflow in the nucleus accumbens shell in awake and freely moving rats using in vivo microdialysis. To scale the biochemical results to the induced electric field in the rat brain, we obtained a realistic simulation of the stimulation scenario using a finite element model. Applying 20 Hz repetitive transcranial magnetic stimulation in 6 trains of 50 stimuli with 280 μs pulse width at a magnetic field strength of 130% of the individual motor threshold, dopamine as well as serotonin outflow in the nucleus accumbens shell significantly increased compared to sham stimulation. Since the electric field decays rapidly with depth in the rat brain, we can conclude that the modulation in neurotransmitter outflow from the nucleus accumbens shell is presumably a remote effect of cortical stimulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Extracellular K+ in the supraoptic nucleus of the rat during reflex bursting activity by oxytocin neurones.

    PubMed Central

    Coles, J A; Poulain, D A

    1991-01-01

    1. We have investigated changes in extracellular potassium concentration [K+]o in the supraoptic nucleus of lactating rats and in particular those that occur during the intense burst of firing by the oxytocin neurones involved in the milk ejection reflex. 2. Double-barrelled K(+)-selective microelectrodes containing a highly selective sensor based on valinomycin were lowered through the exposed cortex towards the supraoptic nucleus (SON) of female rats anaesthetized with urethane. The mean resting [K+]o in the hypothalami of five rats was 2.4 mM, S.D. = 0.3 mM. 3. Where the reference barrel recorded extracellular action potentials from an oxytocin cell, the reflex burst of firing (4 s, typical maximum 50 Hz) was accompanied by a mean increase in [K+]o (delta[K+]o) of 0.22 mM (S.E.M. = 0.02 mM, fifty-seven bursts in eight cells in seven rats). The rise in [K+]o did not begin more than 0.1 s before the onset of the burst, and began to fall from its maximum during the burst. Slow field potentials, indicative of spatial buffering of K+, were undetectable (less than 50 microV). When the electrode was advanced in steps, the amplitudes of both delta[K+]o and the action potential declined steeply to about 10% over a distance of 20 microns: K+ from oxytocin cells appears to be prevented from dispersing freely through the extracellular space of the SON. 4. When the electrode recorded action potentials from a vasopressin cell, delta[K+]o during an oxytocin cell burst was very small: 0.021 mM (S.E.M. = 0.005 mM). At other sites in the SON, where antidromic stimulation evoked a field potential but no action potential, delta[K+]o was 0.047 +/- 0.005 mM. We conclude that the reason oxytocin bursts do not affect vasopressin cells is that [K+]o rises very little around vasopressin cells. A fortiori, since the increases in [K+]o were very small except where action potentials from oxytocin cells were recorded, they can make no significant contribution to synchronizing the onsets of

  5. Assessment of individual differences in the rat nucleus accumbens transcriptome following taste-heroin extended access.

    PubMed

    Imperio, Caesar G; McFalls, Ashley J; Colechio, Elizabeth M; Masser, Dustin R; Vrana, Kent E; Grigson, Patricia S; Freeman, Willard M

    2016-05-01

    Heroin addiction is a disease of chronic relapse that harms the individual through devaluation of personal responsibilities in favor of finding and using drugs. Only some recreational heroin users devolve into addiction but the basis of these individual differences is not known. We have shown in rats that avoidance of a heroin-paired taste cue reliably identifies individual animals with greater addiction-like behavior for heroin. Here rats received 5min access to a 0.15% saccharin solution followed by the opportunity to self-administer either saline or heroin for 6h. Large Suppressors of the heroin-paired taste cue displayed increased drug escalation, motivation for drug, and drug loading behavior compared with Small Suppressors. Little is known about the molecular mechanisms of these individual differences in addiction-like behavior. We examined the individual differences in mRNA expression in the nucleus accumbens (NAc) of rats that were behaviorally stratified by addiction-like behavior using next-generation sequencing. We hypothesized that based on the avoidance of the drug-paired cue there will be a unique mRNA profile in the NAc. Analysis of strand-specific whole genome RNA-Seq data revealed a number of genes differentially regulated in NAc based on the suppression of the natural saccharine reward. Large Suppressors exhibited a unique mRNA prolife compared to Saline controls and Small Suppressors. Genes related to immunity, neuronal activity, and behavior were differentially expressed among the 3 groups. In total, individual differences in avoidance of a heroin-paired taste cue are associated with addiction-like behavior along with differential NAc gene expression.

  6. Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats

    PubMed Central

    Trezza, Viviana; Damsteegt, Ruth; Manduca, Antonia; Petrosino, Stefania; Van Kerkhof, Linda W.M.; Pasterkamp, R. Jeroen; Zhou, Yeping; Campolongo, Patrizia; Cuomo, Vincenzo; Di Marzo, Vincenzo; Vanderschuren, Louk J.M.J.

    2012-01-01

    The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoids in social play behavior, a highly rewarding form of social interaction in adolescent rats. Here, we tested the hypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampus of 4–5 week old male Wistar rats. Furthermore, social play increased phosphorylation of CB1 cannabinoid receptors in the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented the associated elevation in anandamide levels in the amygdala, but not the NAc. Infusion of URB597 into the basolateral amygdala (BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A prevented the play-enhancing effects of systemic administration of URB597. Infusion of URB597 into the NAc also increased social play, but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716A did not affect social play after infusion into the core and shell subregions of the NAc, while it reduced social play when infused into the BLA. These data show that increased anandamide signalling in the amygdala and NAc augments social play, and identify the BLA as a prominent site of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats. PMID:23100412

  7. REM sleep diversity following the pedunculopontine tegmental nucleus lesion in rat.

    PubMed

    Petrovic, Jelena; Lazic, Katarina; Kalauzi, Aleksandar; Saponjic, Jasna

    2014-09-01

    The aim of this study was to demonstrate that two REM clusters, which emerge following bilateral pedunculopontine tegmental nucleus (PPT) lesions in rats, are two functionally distinct REM states. We performed the experiments in Wistar rats, chronically instrumented for sleep recording. Bilateral PPT lesions were produced by the microinfusion of 100 nl of 0.1M ibotenic acid (IBO). Following a recovery period of 2 weeks, we recorded their sleep for 6h. Bilateral PPT lesions were identified by NADPH - diaphorase histochemistry. We applied Fourier analysis to the signals acquired throughout the 6h recordings, and each 10s epoch was differentiated as a Wake, NREM or REM state. We analyzed the topography of the sleep/wake states architecture and their transition structure, their all state-related EEG microstructures, and the sensorimotor (SMCx) and motor (MCx) cortex REM related cortico-muscular coherences (CMCs). Bilateral PPT lesion in rats increased the likelihood of the emergence of two distinct REM sleep states, specifically expressed within the MCx: REM1 and REM2. Bilateral PPT lesion did not change the sleep/wake states architecture of the SMCx, but pathologically increased the duration of REM1 within the MCx, alongside increasing Wake/REM1/Wake and NREM/REM2/NREM transitions within both cortices. In addition, the augmented total REM SMCx EEG beta amplitude and REM1 MCx EEG theta amplitude was the underlying EEG microstructure pathology. PPT lesion induced REM1 and REM2 are differential states with regard to total EMG power, topographically distinct EEG microstructures, and locomotor drives to nuchal musculature.

  8. Positive reinforcing effect of oxytocin microinjection in the rat central nucleus of amygdala.

    PubMed

    László, K; Kovács, A; Zagoracz, O; Ollmann, T; Péczely, L; Kertes, E; Lacy, D G; Lénárd, L

    2016-01-01

    Neuropeptide oxytocin (OT) receives increasing attention since, it plays a role in various behaviors including anxiety, drug addiction, learning, social recognition, empathy, pair bonding and decreased aggression. The central nucleus of the amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. CeA was shown to be rich in OT-receptors (OTR). The aim of our study was to examine the possible effects of OT and OTR antagonist in the CeA on reinforcement using the conditioned place preference test and on anxiety using the elevated plus maze test. Male Wistar rats were microinjected bilaterally with 10 ng OT or 100 ng OT (Sigma: O6379, injected in volume of 0.4μl) or 10ng OTR antagonist (Sigma: L-2540) alone, or OTR antagonist 15 min prior 10 ng OT treatment or vehicle solution into the CeA. Rats receiving 10 ng OT spent significantly more time in the treatment quadrant during the test session, while 100 ng OT treatment produced no effect. Prior treatment with the non-peptide OTR antagonist blocked the effects of OT. The antagonist in itself did not influence the place preference. The elevated plus maze test revealed that 10 ng OT significantly increased the time spent in the open arms. OTR antagonist pre-treatment could inhibit this effect and the antagonist in itself did not affect the time spent in the open arms. Our results show that in the rat CeA OT has dose-dependent, positive reinforcing and anxiolytic effects, via OTR demonstrated by the blocking effects of selective OTR antagonist.

  9. Oxytocin in the nucleus accumbens core reduces reinstatement of methamphetamine-seeking behaviour in rats.

    PubMed

    Baracz, Sarah J; Everett, Nicholas A; McGregor, Iain S; Cornish, Jennifer L

    2016-03-01

    The psychostimulant methamphetamine (METH) is an addictive illicit drug. Systemic administration of the neuropeptide oxytocin modulates METH-related reward and METH-seeking behaviour. Recent findings demonstrated a reduction in METH-induced reward by oxytocin administration into the nucleus accumbens (NAc) core. It is not known, however, if oxytocin acts in this region to reduce relapse to METH-seeking behaviour. Using the drug reinstatement paradigm in rats experienced at METH self-administration, we aimed to determine whether oxytocin pre-treatment within the NAc core would reduce relapse to METH use and if this could be reversed by the co-administration of the oxytocin receptor (OTR) antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague-Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae in the NAc core. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour fixed ratio 1 scheduled sessions for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.5 pmol, 1.5 pmol, 4.5 pmol) or co-administration of oxytocin (1.5 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (1 nmol, 3 nmol) in the NAc core (500 nl/side) was examined on METH-primed (1 mg/kg, i.p.) reinstatement of drug-seeking behaviour. Our results showed oxytocin directly administered into the NAc core decreased METH-primed reinstatement in a dose-dependent manner. Co-administration of the selective OTR antagonist did not specifically reverse the inhibitory effects of oxytocin on METH priming, suggesting mediation by receptors other than the OTR. These findings highlight an important modulatory effect of oxytocin in the NAc core on relapse to METH seeking.

  10. Enhancement of oscillatory activity in the endopiriform nucleus of rats raised under abnormal oral conditions.

    PubMed

    Yoshimura, Hiroshi; Hasumoto-Honjo, Miho; Sugai, Tokio; Segami, Natsuki; Kato, Nobuo

    2014-02-21

    Endopiriform nucleus (EPN) is located deep to the piriform cortex, and has neural connections with not only neighboring sensory areas but also subcortical areas where emotional and nociceptive information is processed. Well-balanced oral condition might play an important role in stability of brain activities. When the oral condition is impaired, several areas in the brain might be affected. In the present study, we investigated whether abnormal conditions of oral region influence neural activities in the EPN. Orthodontic appliance that generates continuous force and chronic pain-related stress was fixed to maxillary incisors of rats, and raised. Field potential recordings were made from the EPN of brain slices. We previously reported that the EPN has an ability to generate membrane potential oscillation. In the present study, we have applied the same methods to assess activities of neuron clusters in the EPN. In the case of normal rats, stable field potential oscillations were induced in the EPN by application of low-frequency electrical stimulation under the medium with caffeine. In the case of rats with the orthodontic appliance, stable field potential oscillations were also induced, but both duration of oscillatory activities and wavelet number were increased. The enhanced oscillations were depressed by blockade of NMDA receptors. Thus, impairment of oral health under application of continuous orthodontic force and chronic pain-related stress enhanced neural activities in the EPN, in which up-regulation of NMDA receptors may be concerned. These findings suggest that the EPN might be involved in information processing with regard to abnormal conditions of oral region.

  11. Allopregnanolone in the bed nucleus of the stria terminalis modulates contextual fear in rats

    PubMed Central

    Nagaya, Naomi; Acca, Gillian M.; Maren, Stephen

    2015-01-01

    Trauma- and stress-related disorders are among the most common types of mental illness affecting the U.S. population. For many of these disorders, there is a striking sex difference in lifetime prevalence; for instance, women are twice as likely as men to be affected by posttraumatic stress disorder (PTSD). Gonadal steroids and their metabolites have been implicated in sex differences in fear and anxiety. One example, allopregnanolone (ALLO), is a neuroactive metabolite of progesterone that allosterically enhances GABAA receptor activity and has anxiolytic effects. Like other ovarian hormones, it not only occurs at different levels in males and females but also fluctuates over the female reproductive cycle. One brain structure that may be involved in neuroactive steroid regulation of fear and anxiety is the bed nucleus of the stria terminalis (BNST). To explore this question, we examined the consequences of augmenting or reducing ALLO activity in the BNST on the expression of Pavlovian fear conditioning in rats. In Experiment 1, intra-BNST infusions of ALLO in male rats suppressed freezing behavior (a fear response) to the conditioned context, but did not influence freezing to a discrete tone conditioned stimulus (CS). In Experiment 2, intra-BNST infusion of either finasteride (FIN), an inhibitor of ALLO synthesis, or 17-phenyl-(3α,5α)-androst-16-en-3-ol, an ALLO antagonist, in female rats enhanced contextual freezing; neither treatment affected freezing to the tone CS. These findings support a role for ALLO in modulating contextual fear via the BNST and suggest that sex differences in fear and anxiety could arise from differential steroid regulation of BNST function. The susceptibility of women to disorders such as PTSD may be linked to cyclic declines in neuroactive steroid activity within fear circuitry. PMID:26300750

  12. Allopregnanolone in the bed nucleus of the stria terminalis modulates contextual fear in rats.

    PubMed

    Nagaya, Naomi; Acca, Gillian M; Maren, Stephen

    2015-01-01

    Trauma- and stress-related disorders are among the most common types of mental illness affecting the U.S. population. For many of these disorders, there is a striking sex difference in lifetime prevalence; for instance, women are twice as likely as men to be affected by posttraumatic stress disorder (PTSD). Gonadal steroids and their metabolites have been implicated in sex differences in fear and anxiety. One example, allopregnanolone (ALLO), is a neuroactive metabolite of progesterone that allosterically enhances GABAA receptor activity and has anxiolytic effects. Like other ovarian hormones, it not only occurs at different levels in males and females but also fluctuates over the female reproductive cycle. One brain structure that may be involved in neuroactive steroid regulation of fear and anxiety is the bed nucleus of the stria terminalis (BNST). To explore this question, we examined the consequences of augmenting or reducing ALLO activity in the BNST on the expression of Pavlovian fear conditioning in rats. In Experiment 1, intra-BNST infusions of ALLO in male rats suppressed freezing behavior (a fear response) to the conditioned context, but did not influence freezing to a discrete tone conditioned stimulus (CS). In Experiment 2, intra-BNST infusion of either finasteride (FIN), an inhibitor of ALLO synthesis, or 17-phenyl-(3α,5α)-androst-16-en-3-ol, an ALLO antagonist, in female rats enhanced contextual freezing; neither treatment affected freezing to the tone CS. These findings support a role for ALLO in modulating contextual fear via the BNST and suggest that sex differences in fear and anxiety could arise from differential steroid regulation of BNST function. The susceptibility of women to disorders such as PTSD may be linked to cyclic declines in neuroactive steroid activity within fear circuitry.

  13. Effects of clonidine injections into the bed nucleus of the stria terminalis on fear and anxiety behavior in rats.

    PubMed

    Schweimer, Judith; Fendt, Markus; Schnitzler, Hans-Ulrich

    2005-01-10

    Emotions such as fear and anxiety are mediated by a neural network containing nuclei like the amygdala, the bed nucleus of the stria terminalis and the periaqueductal gray. Noradrenaline is a neurotransmitter closely connected with the processing of stimuli eliciting these emotions. The bed nucleus of the stria terminalis contains the highest density of noradrenaline within the brain. In the present study, we investigated effects of injections of the noradrenergic alpha2-adrenoceptor agonist clonidine into the bed nucleus of the stria terminalis on learned and unlearned fear (anxiety) in rats on different animal models of fear and anxiety: acquisition and expression of fear-potentiated startle, sensitization of the acoustic startle response by foot shocks and light-enhanced startle. Clonidine injections disrupted acquisition and expression of fear-potentiated startle, as well as light-enhanced startle, whereas sensitization was not affected. These results indicate that noradrenaline within the bed nucleus of the stria terminalis mediates both fear and anxiety. We suggest that there is rather a neurochemical than a neuroanatomical dissociation between learned fear and anxiety as hypothesized by Walker and Davis (Walker, D.L. and M. Davis, 1997b, Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear, J. Neurosci. 17, 9375-9383.).

  14. Steroid sulfatase deficiency with bilateral periventricular nodular heterotopia.

    PubMed

    Ozawa, Hiroshi; Osawa, Maki; Nagai, Toshiro; Sakura, Nobuo

    2006-03-01

    This report presents a case of steroid sulfatase deficiency with bilateral periventricular nodular heterotopia. A 13-year-old male was diagnosed as having steroid sulfatase deficiency because steroid sulfatase activity was not detected in his leukocytes. In deoxyribonucleic acid studies, steroid sulfatase locus and adjacent loci were found to be deleted in his deoxyribonucleic acid. Cranial magnetic resonance imaging revealed periventricular nodular heterotopia, disclosing an irregular contour of the lateral walls of the lateral ventricles due to small nodular masses that were isointense as to the gray matter. In steroid sulfatase deficiency patients, bilateral periventricular nodular heterotopia must be considered.

  15. Exogenous corticosterone induces the expression of the clock protein, PERIOD2, in the oval nucleus of the bed nucleus of the stria terminalis and the central nucleus of the amygdala of adrenalectomized and intact rats.

    PubMed

    Segall, Lauren A; Amir, Shimon

    2010-10-01

    The cyclical expression of the clock protein PERIOD2 (PER2) in select regions of the limbic forebrain is contingent upon the rhythmic secretion of the adrenal glucocorticoid, corticosterone. Daily rhythmic PER2 expression in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and the central nucleus of the amygdala (CEA) is abolished with the removal of the adrenal glands but restored with rhythmic hormone replacement via the drinking water at a time corresponding to the endogenous peak of circulating glucocorticoids. Here, we investigated the effects of serial or acute systemic injections of corticosterone on the expression of PER2 in the BNSTov and CEA of both adrenalectomized (ADX) and intact rats. We sought to determine whether there is a temporal window of corticosterone sensitivity by delivering the hormone at a time corresponding to trough levels of circulating glucocorticoids, at lights on. We found that daily morning injections of corticosterone induced PER2 expression in the BNSTov and CEA of ADX rats, with levels peaking 1 h after injection. In intact rats, daily morning injections significantly upregulated the expression of PER2 in the BNSTov and CEA 1 h after injection and dampened the evening peak, while a single injection abolished the rhythm of PER2 expression in the CEA but had no effect on PER2 in the BNSTov. Our findings suggest that despite the potential masking effect of signals from the light-entrained master clock, daytime chronic and acute corticosterone administration can alter the rhythmic expression of PER2 in the BNSTov and CEA, and that the response is region-specific and dependent on the duration of treatment.

  16. 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.

  17. Aberrant high frequency oscillations recorded in the rat nucleus accumbens in the methylazoxymethanol acetate neurodevelopmental model of schizophrenia.

    PubMed

    Goda, Sailaja A; Olszewski, Maciej; Piasecka, Joanna; Rejniak, Karolina; Whittington, Miles A; Kasicki, Stefan; Hunt, Mark J

    2015-08-03

    Altered activity of the nucleus accumbens (NAc) is thought to be a core feature of schizophrenia and animal models of the disease. Abnormal high frequency oscillations (HFO) in the rat NAc have been associated with pharmacological models of schizophrenia, in particular the N-methyl-d-aspartate receptor (NMDAR) hypofunction model. Here, we tested the hypothesis that abnormal HFO are also associated with a neurodevelopmental rat model. Using prenatal administration of the mitotoxin methylazoxymethanol acetate (MAM) we obtained the offspring MAM rats. Adult MAM and Sham rats were implanted with electrodes, for local field potential recordings, in the NAc. Spontaneous HFO (spHFO) in MAM rats were characterized by increased power and frequency relative to Sham rats. MK801 dose-dependently increased the power of HFO in both groups. However, the dose-dependent increase in HFO frequency found in Sham rats was occluded in MAM rats. The antipsychotic compound, clozapine reduced the frequency of HFO which was similar in both MAM and Sham rats. Further, HFO were modulated in a similar manner by delta oscillations in both MAM and Sham rats. Together these findings suggest that increased HFO frequency represents an important feature in certain animal models of schizophrenia. These findings support the hypothesis that altered functioning of the NAc is a core feature in animal models of schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Oleic acid synthesized by stearoyl-CoA desaturase (SCD-1) in the lateral periventricular zone of the developing rat brain mediates neuronal growth, migration and the arrangement of prospective synapses.

    PubMed

    Polo-Hernández, Erica; Tello, Vega; Arroyo, Angel A; Domínguez-Prieto, Marta; de Castro, Fernando; Tabernero, Arantxa; Medina, José M

    2014-06-27

    Our previous work has shown that oleic acid synthesized by astrocytes in response to serum albumin behaves as a neurotrophic factor in neurons, upregulating the expression of GAP-43 and MAP-2 proteins, which are respectively markers of axonal and dendrite growth. In addition, oleic acid promoted neuron migration and aggregation, resulting in clusters of neurons connected each other by the newly formed neurites. In this work we show that the presence of albumin or albumin plus oleic acid increases neuron migration in cultured explants of the lateral periventricular zone, resulting in an increase in the number of GAP-43-positive neurons leaving the explant. Upon silencing stearoyl-CoA desaturase-1 (SCD-1), a key enzyme in oleic acid synthesis by RNA of interference mostly prevented the effect of albumin but not that of albumin plus oleic acid, suggesting that the oleic acid synthesized due to the effect of albumin would be responsible for the increase in neuron migration. Oleic acid increased doublecortin (DCX) expression in cultured neurons, explants and organotypic slices, suggesting that DCX may mediate in the effect of oleic acid on neuron migration. The effect of oleic acid on neuron migration may be destined for the formation of synapses because the presence of oleic acid increased the expression of synaptotagmin and that of postsynaptic density protein (PDS-95), respectively markers of the pre- and postsynaptic compartments. In addition, confocal microscopy revealed the occurrence of points of colocalization between synaptotagmin and PDS-95, which is consistent with the idea that oleic acid promotes synapse arrangement.

  19. The Arcuate Nucleus: A Site of Fast Negative Feedback for Corticosterone Secretion in Male Rats.

    PubMed

    Leon-Mercado, Luis; Herrera Moro Chao, Daniela; Basualdo, María Del Carmen; Kawata, Mitsuhiro; Escobar, Carolina; Buijs, Ruud M

    2017-01-01

    Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of the hypothalamus (PVN), mainly via the sympathetic autonomic nervous system (ANS) directly stimulating Cort release from the adrenal gland and via corticotropin-releasing hormone targeting the adenohypophysis to release adrenocorticotropic hormone (ACTH). Cort feeds back through glucocorticoid receptors (GRs). Here we show in male Wistar rats that PVN neurons projecting to the adrenal gland do not express GRs, leaving the question of how the ANS in the PVN gets information about circulating Cort levels to control the adrenal. Since the arcuate nucleus (ARC) shows a less restrictive blood-brain barrier, expresses GRs, and projects to the PVN, we investigated whether the ARC can detect and produce fast adjustments of circulating Cort. In low Cort conditions (morning), local microdialysis in the ARC with type I GR antagonist produced a fast and sustained increase of Cort. This was not observed with a type II antagonist. At the circadian peak levels of Cort (afternoon), a type II GR antagonist, but not a type I antagonist, increased Cort levels but not ACTH levels. Antagonist infusions in the PVN did not modify circulating Cort levels, demonstrating the specificity of the ARC to give Cort negative feedback. Furthermore, type I and II GR agonists in the ARC prevented the increase of Cort after stress, demonstrating the role of the ARC as sensor to modulate Cort release. Our findings show that the ARC may be essential to sense blood levels of Cort and adapt Cort secretion depending on such conditions as stress or time of day.

  20. Temporal coding of taste in the parabrachial nucleus of the pons of the rat.

    PubMed

    Rosen, Andrew M; Victor, Jonathan D; Di Lorenzo, Patricia M

    2011-04-01

    Recent studies have provided evidence that temporal coding contributes significantly to encoding taste stimuli at the first central relay for taste, the nucleus of the solitary tract (NTS). However, it is not known whether this coding mechanism is also used at the next synapse in the central taste pathway, the parabrachial nucleus of the pons (PbN). In the present study, electrophysiological responses to taste stimuli (sucrose, NaCl, HCl, and quinine) were recorded from 44 cells in the PbN of anesthetized rats. In 29 cells, the contribution of the temporal characteristics of the response to the discrimination of various taste qualities was assessed. A family of metrics that quantifies the similarity of two spike trains in terms of spike count and spike timing was used. Results showed that spike timing in 14 PbN cells (48%) conveyed a significant amount of information about taste quality, beyond what could be conveyed by spike count alone. In another 14 cells (48%), the rate envelope (time course) of the response contributed significantly more information than spike count alone. Across cells there was a significant correlation (r = 0.51; P < 0.01) between breadth of tuning and the proportion of information conveyed by temporal dynamics. Comparison with previous data from the NTS (Di Lorenzo PM and Victor JD. J Neurophysiol 90: 1418-31, 2003 and J Neurophysiol 97: 1857-1861, 2007) showed that temporal coding in the NTS occurred in a similar proportion of cells and contributed a similar fraction of the total information at the same average level of temporal precision, even though trial-to-trial variability was higher in the PbN than in the NTS. These data suggest that information about taste quality conveyed by the temporal characteristics of evoked responses is transmitted with high fidelity from the NTS to the PbN.

  1. The Arcuate Nucleus: A Site of Fast Negative Feedback for Corticosterone Secretion in Male Rats

    PubMed Central

    Kawata, Mitsuhiro; Escobar, Carolina

    2017-01-01

    Abstract Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of the hypothalamus (PVN), mainly via the sympathetic autonomic nervous system (ANS) directly stimulating Cort release from the adrenal gland and via corticotropin-releasing hormone targeting the adenohypophysis to release adrenocorticotropic hormone (ACTH). Cort feeds back through glucocorticoid receptors (GRs). Here we show in male Wistar rats that PVN neurons projecting to the adrenal gland do not express GRs, leaving the question of how the ANS in the PVN gets information about circulating Cort levels to control the adrenal. Since the arcuate nucleus (ARC) shows a less restrictive blood–brain barrier, expresses GRs, and projects to the PVN, we investigated whether the ARC can detect and produce fast adjustments of circulating Cort. In low Cort conditions (morning), local microdialysis in the ARC with type I GR antagonist produced a fast and sustained increase of Cort. This was not observed with a type II antagonist. At the circadian peak levels of Cort (afternoon), a type II GR antagonist, but not a type I antagonist, increased Cort levels but not ACTH levels. Antagonist infusions in the PVN did not modify circulating Cort levels, demonstrating the specificity of the ARC to give Cort negative feedback. Furthermore, type I and II GR agonists in the ARC prevented the increase of Cort after stress, demonstrating the role of the ARC as sensor to modulate Cort release. Our findings show that the ARC may be essential to sense blood levels of Cort and adapt Cort secretion depending on such conditions as stress or time of day. PMID:28275717

  2. Anatomical evidence for a ponto-septal pathway via the nucleus incertus in the rat.

    PubMed

    Teruel-Martí, Vicent; Cervera-Ferri, Ana; Nuñez, Angel; Valverde-Navarro, Alfonso Amador; Olucha-Bordonau, Francisco Eliseo; Ruiz-Torner, Amparo

    2008-07-07

    Hippocampal theta activity is involved in sensory-motor integration and constitutes a functional basis for mnemonic functions. The medial septum-diagonal band of Broca (MS/DBv) is a key structure as pacemaker of the oscillation. In addition, some brainstem reticular structures are crucial for the activation of MS/DBv. Specifically, the nucleus reticularis pontis oralis (RPO) is considered the most effective pontine site for eliciting theta rhythm. Nevertheless, its connection with the MS/DBv is not direct. A previous study by our group pointed out that the nucleus incertus (NI) could be considered as a relay in this multisynaptic pathway. From this study, the stimulation of RPO increased the discharge rate of NI neurons in anesthetized rats and the lesion of the NI suppressed the RPO-elicited hippocampal theta. Those findings suggested a projection from RPO to NI, although the existing literature did not support this hypothesis. In order to clarify the dichotomy between the anatomical and the electrophysiological data, we performed a set of tracing studies. Anterograde tracer injections into RPO showed a profuse projection to NI. This connection was confirmed by retrograde tracer injections into NI. Injections of retrograde tracer in MS/DBv confirmed the intense NI-MS/DBv projection. Furthermore, simultaneous injections of anterograde and retrograde tracers into RPO and MS/DBv respectively resulted in a high-correlated pattern of terminal-like fibers over labeled somata in the NI. This study provides the first anatomical evidence of a ponto-septal pathway via the NI that contributes to generation and modulation the hippocampal theta activity.

  3. Theta synchronization between the hippocampus and the nucleus incertus in urethane-anesthetized rats.

    PubMed

    Cervera-Ferri, Ana; Guerrero-Martínez, Juan; Bataller-Mompeán, Manuel; Taberner-Cortes, Alida; Martínez-Ricós, Joana; Ruiz-Torner, Amparo; Teruel-Martí, Vicent

    2011-06-01

    Oscillatory coupling between distributed areas can constitute a mechanism for neuronal integration. Theta oscillations provide temporal windows for hippocampal processing and only appear during certain active states of animals. Since previous studies have demonstrated that nucleus incertus (NI) contributes to the generation of hippocampal theta activity, in this paper, we evaluated the oscillatory coupling between both structures. We compared hippocampal and NI field potentials that were simultaneously recorded in urethane-anesthetized rats. Electrical and cholinergic stimulations of the reticularis pontis oralis nucleus have been used as hippocampal theta generation models. The spectral analyses reveal that electrical stimulation induced an increase in theta oscillations in both channels, whose frequencies depended on the intensity of stimulation. The intensity range used simultaneously increased the normalized spectral energy in the fast theta band (6-12 Hz) in HPC and NI. Frequencies within the theta range were found to be very similar in both channels. In order to validate coupling, spectral coherence was inspected. The data reveal that coherence in the high theta band also increased while stimuli were applied. Cholinergic activation progressively increased the main frequency in both structures to reach an asymptotic period with stable peak frequency in the low theta range (3-6 Hz), which could be first observed in NI and lasted about 1,500 s. Coherence in this band reached values close to 1. Taken together, these results support an electrophysiological and functional coupling between the hippocampus and the reticular formation, suggesting NI to be part of a distributed network working at theta frequencies.

  4. Inhibitory control of nociceptive responses of trigeminal spinal nucleus cells by somatosensory corticofugal projection in rat.

    PubMed

    Malmierca, E; Martin, Y B; Nuñez, A

    2012-09-27

    The caudal division of the trigeminal spinal nucleus (Sp5C) is an important brainstem relay station of orofacial pain transmission. The aim of the present study was to examine the effect of cortical electrical stimulation on nociceptive responses in Sp5C neurons. Extracellular recordings were performed in the Sp5C nucleus by tungsten microelectrodes in urethane-anesthetized Sprague-Dawley rats. Nociceptive stimulation was produced by application of capsaicin cream on the whisker pad or by constriction of the infraorbital nerve. Capsaicin application evoked a long-lasting increase in the spontaneous firing rate from 1.4±0.2 to 3.4±0.6 spikes/s. Non-noxious tactile responses from stimuli delivered to the receptive field (RF) center decreased 5 min. after capsaicin application (from 2.3±0.1 to 1.6±0.1 spikes/stimulus) while responses from the whisker located at the RF periphery increased (from 1.3±0.2 to 2.0±0.1 spikes/stimulus under capsaicin). Electrical train stimulation of the primary (S1) or secondary (S2) somatosensory cortical areas reduced the increase in the firing rate evoked by capsaicin. Also, S1, but not S2, cortical stimulation reduced the increase in non-noxious tactile responses from the RF periphery. Inhibitory cortical effects were mediated by the activation of GABAergic and glycinergic neurons because they were blocked by bicuculline or strychnine. The S1 and S2 cortical stimulation also inhibited Sp5C neurons in animals with constriction of the infraorbital nerve. Consequently, the corticofugal projection from S1 and S2 cortical areas modulates nociceptive responses of Sp5C neurons and may control the transmission of nociceptive sensory stimulus.

  5. Cholinergic and non-cholinergic mesopontine tegmental neurons projecting to the subthalamic nucleus in the rat

    PubMed Central

    Kita, Takako; Kita, Hitoshi

    2010-01-01

    The subthalamic nucleus (STN) receives cholinergic and non-cholinergic projections from the mesopontine tegmentum. This study investigated the numbers and distributions of neurons involved in these projections in rats using Fluorogold (FG) retrograde tracing combined with immunostaining of choline acetyltransferase and a neuron-specific nuclear protein. The results suggest that a small population of cholinergic neurons mainly in the caudoventral part of the pedunculopontine tegmental nucleus (PPN), approximately 360 neurons (≈10% of total) in the homolateral and 80 neurons (≈2%) in the contralateral PPN, projects to the STN. In contrast, the number of non-cholinergic neurons projecting to the STN was estimated to be 9 times as much, with approximately 3300 in the homolateral side and 1300 neurons in the contralateral side. A large gathering of the FG-labeled non-cholinergic neurons was found rostrodorsomedial to the caudolateral PPN. The biotinylated dextran amine (BDA) anterograde tracing method was used to substantiate the mesopontine-STN projections. Injection of BDA into the caudoventral PPN labeled numerous thin fibers with small en-passant varicosities in the STN. Injection of BDA into the non-cholinergic neuron-rich area labeled a moderate number of thicker fibers with patches of aggregates of larger boutons. The densities of labeled fibers and the number of retrogradely labeled cells in the mesopontine tegmentum suggested that the terminal field formed in the STN by each cholinergic neuron is more extensive than that by each non-cholinergic neuron. The findings suggest that cholinergic and non-cholinergic mesopontine afferents may carry different information to the STN. PMID:21198985

  6. Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y

    PubMed Central

    Taksande, BG; Kotagale, NR; Nakhate, KT; Mali, PD; Kokare, DM; Hirani, K; Subhedar, NK; Chopde, CT; Ugale, RR

    2011-01-01

    BACKGROUND AND PURPOSE Agmatine, a multifaceted neurotransmitter, is abundantly expressed in the hypothalamic paraventricular nucleus (PVN). Our aim was to assess (i) the effect of agmatine on feeding behaviour and (ii) its association, if any, with neuropeptide Y (NPY). EXPERIMENTAL APPROACH Satiated rats fitted with intra-PVN cannulae were administered agmatine, alone or jointly with (i) α2-adrenoceptor agonist, clonidine, or antagonist, yohimbine; (ii) NPY, NPY Y1 receptor agonist, [Leu31, Pro34]-NPY, or antagonist, BIBP3226; or (iii) yohimbine and NPY. Cumulative food intake was monitored at different post-injection time points. Furthermore, the expression of hypothalamic NPY following i.p. treatment with agmatine, alone or in combination with yohimbine (i.p.), was evaluated by immunocytochemistry. KEY RESULTS Agmatine robustly increased feeding in a dose-dependent manner. While pretreatment with clonidine augmented, yohimbine attenuated the orexigenic response to agmatine. Similarly, NPY and [Leu31, Pro34]-NPY potentiated the agmatine-induced hyperphagia, whereas BIBP3226 inhibited it. Moreover, yohimbine attenuated the synergistic orexigenic effect induced by the combination of NPY and agmatine. Agmatine increased NPY immunoreactivity in the PVN fibres and in the cells of the hypothalamic arcuate nucleus (ARC) and this effect was prevented by pretreatment with yohimbine. NPY immunoreactivity in the fibres of the ARC, dorsomedial, ventromedial and lateral nuclei of the hypothalamus was not affected by any of the above treatments. CONCLUSIONS AND IMPLICATIONS The orexigenic effect of agmatine is coupled to increased NPY activity mediated by stimulation of α2-adrenoceptors within the PVN. This signifies the importance of agmatine or α2-adrenoceptor modulators in the development of novel therapeutic agents to treat feeding-related disorders. PMID:21564088

  7. Voluntary alcohol drinking enhances proopiomelanocortin (POMC) gene expression in nucleus accumbens shell and hypothalamus of Sardinian alcohol-preferring rats

    PubMed Central

    Zhou, Yan; Colombo, Giancarlo; Niikura, Keiichi; Carai, Mauro AM; Femenía, Teresa; García-Gutiérrez, Maria S; Manzanares, Jorge; Ho, Ann; Gessa, Gian Luigi; Kreek, Mary Jeanne

    2013-01-01

    Background Evidence obtained in humans and rodents indicates that beta-endorphin [encoded by the proopiomelanocortin (POMC) gene] is critical in regulation of alcohol drinking behavior. However, the alcohol effect on POMC gene expression has not been studied in rodent mesolimbic regions, such as the nucleus accumbens (NAc). Methods In this study, we first utilized POMC-EGFP transgenic mice to visualize POMC neurons, and found that POMC-EGFP cells were modestly distributed throughout the NAc shell and core, in addition to the hypothalamic arcuate nucleus. POMC mRNA expression in the NAc of mice and rats was confirmed using RT-PCR and solution hybridization assays. We then investigated whether there are genetically determined differences in basal mRNA levels of POMC and mu opioid receptor (MOP-r) between selectively bred Sardinian alcohol-preferring (sP) and non-preferring (sNP) rats, and whether these mRNA levels are altered in sP rats after alcohol drinking (10%, unlimited access) for 17 days. Results Alcohol-naive sP rats had higher basal POMC mRNA levels than sNP rats only in hypothalamus. Alcohol drinking increased POMC mRNA levels in both the NAc shell (by 100%) and hypothalamus (by 50%) of sP rats. Although sP rats had lower basal levels of MOP-r mRNA and GTPγS binding in NAc shell than sNP rats, voluntary alcohol consumption had no effect on MOP-r mRNA levels in the NAc shell. Conclusions Our results define the distribution of POMC-expressing neurons in the NAc of mice and rats. Higher POMC expression at basal levels in alcohol-preferring sP rats (genetically determined), along with increases after drinking (alcohol-induced) in the NAc shell and hypothalamus, suggest that the POMC systems play a role in high alcohol preference and consumption. PMID:22724395

  8. Characteristics of rostral solitary tract nucleus neurons with identified afferent connections that project to the parabrachial nucleus in rats.

    PubMed

    Suwabe, Takeshi; Bradley, Robert M

    2009-07-01

    Afferent information derived from oral chemoreceptors is transmitted to second-order neurons in the rostral solitary tract nucleus (rNST) and then relayed to other CNS locations responsible for complex sensory and motor behaviors. Here we investigate the characteristics of rNST neurons sending information rostrally to the parabrachial nucleus (PBN). Afferent connections to these rNST-PBN projection neurons were identified by anterograde labeling of the chorda tympani (CT), glossopharyngeal (IX), and lingual (LV) nerves. We used voltage- and current-clamp recordings in brain slices to characterize the expression of both the transient A-type potassium current, IKA and the hyperpolarization-activated inward current, Ih, important determinants of neuronal repetitive discharge characteristics. The majority of rNST-PBN neurons express IKA, and these IKA-expressing neurons predominate in CT and IX terminal fields but were expressed in approximately half of the neurons in the LV field. rNST-PBN neurons expressing Ih were evenly distributed among CT, IX and LV terminal fields. However, expression patterns of IKA and Ih differed among CT, IX, and LV fields. IKA-expressing neurons frequently coexpress Ih in CT and IX terminal fields, whereas neurons in LV terminal field often express only Ih. After GABAA receptor block all rNST-PBN neurons responded to afferent stimulation with all-or-none excitatory synaptic responses. rNST-PBN neurons had either multipolar or elongate morphologies and were distributed throughout the rNST, but multipolar neurons were more often encountered in CT and IX terminal fields. No correlation was found between the biophysical and morphological characteristics of the rNST-PBN projection neurons in each terminal field.

  9. An investigation of the origin of extracellular GABA in rat nucleus accumbens measured in vivo by microdialysis.

    PubMed

    Smith, S E; Sharp, T

    1994-01-01

    GABA transmission in the nucleus accumbens is believed to play a central role in motivational processes and the expression of psychostimulant drug action. Here we report measurements of extracellular GABA in nucleus accumbens of the rat and investigate its origin. Extracellular GABA was detected using microdialysis in combination with a novel HPLC-based assay. In the awake rat, GABA in the microdialysates (1) increased 10-fold following perfusion with 0.5 mM nipecotic acid, a GABA releasing agent and uptake blocker, (2) increased 7-fold following local perfusion with 50 mM KCl, (3) decreased 50% following perfusion with tetrodotoxin, (4) decreased 50% following perfusion with a Ca(2+(-free medium and (5) decreased 40% following perfusion with high (12.5 mM) MgCl. Finally, in the anaesthetized rat, GABA in the microdialysates decreased 50% following i.p. injection of 100 mg/kg 3-mercaptoproprionic acid, a GABA synthesis inhibitor. We conclude that GABA in microdialysates from nucleus accumbens of the rat (awake) responds appropriately to selected pharmacological agents and derives at least in part (50%) from neurones.

  10. Increased sucrose intake and corresponding c-Fos in amygdala and parabrachial nucleus of dietary obese rats.

    PubMed

    Li, Jinrong; Chen, Ke; Yan, Jianqun; Wang, Qian; Zhao, Xiaolin; Yang, Xuejuan; Yang, Dejun; Zhao, Shiru; Zhu, Guangjing; Sun, Bo

    2012-09-13

    The intake-excitatory effects of caloric foods are mainly due to the palatable taste and the ensuing positive postingestive effects. Dietary obese individuals are inclined to overeat high caloric foods. However, it is still unclear whether the taste or postingestive reinforcement mainly contributes to the excessive intake by obese individuals. In the present study, we measured 10- or 120-min sucrose solution drunk by dietary obese rats and measured c-Fos expression following 120-min tests in the central nucleus of amygdala (CeA), a forebrain nucleus involved in the hedonic reward and craving, and the parabrachial nucleus (PBN), a taste relay area responsive to positive postingestive effects. Dietary obese rats, compared with those fed normal chow, ingested larger amounts of sucrose solution (0.25 M) in the 120-min test, but not in the 10-min test. In addition, significantly more sucrose-induced c-Fos positive cells were found in the CeA, but much less in the external lateral subnucleus of the PBN of dietary obese rats. Our results demonstrate that increased sucrose intake in dietary obese rats is mainly due to the alteration of postingestive effects. The differences in these postingestive effects in obesity may involve greater positive/excitatory signals in which the CeA may play a role, and less negative/inhibitory signals in which the el-PBN may be involved.

  11. The effect of nucleus basalis magnocellularis deep brain stimulation on memory function in a rat model of dementia.

    PubMed

    Lee, Ji Eun; Jeong, Da Un; Lee, Jihyeon; Chang, Won Seok; Chang, Jin Woo

    2016-01-12

    Deep brain stimulation has recently been considered a potential therapy in improving memory function. It has been shown that a change of neurotransmitters has an effect on memory function. However, much about the exact underlying neural mechanism is not yet completely understood. We therefore examined changes in neurotransmitter systems and spatial memory caused by stimulation of nucleus basalis magnocellularis in a rat model of dementia. We divided rats into four groups: Normal, Lesion, Implantation, and Stimulation. We used 192 IgG-saporin for degeneration of basal forebrain cholinergic neuron related with learning and memory and it was injected into all rats except for the normal group. An electrode was ipsilaterally inserted in the nucleus basalis magnocellularis of all rats of the implantation and stimulation group, and the stimulation group received the electrical stimulation. Features were verified by the Morris water maze, immunochemistry and western blotting. All groups showed similar performances during Morris water maze training. During the probe trial, performance of the lesion and implantation group decreased. However, the stimulation group showed an equivalent performance to the normal group. In the lesion and implantation group, expression of glutamate acid decarboxylase65&67 decreased in the medial prefrontal cortex and expression of glutamate transporters increased in the medial prefrontal cortex and hippocampus. However, expression of the stimulation group showed similar levels as the normal group. The results suggest that nucleus basalis magnocellularis stimulation enhances consolidation and retrieval of visuospatial memory related to changes of glutamate acid decarboxylase65&67 and glutamate transporter.

  12. Transient calcium-dependent potassium current in magnocellular neurosecretory cells of the rat supraoptic nucleus.

    PubMed

    Bourque, C W

    1988-03-01

    1. Magnocellular neurosecretory neurones were impaled in the supraoptic nucleus of perfused explants of rat hypothalamus. Membrane currents were studied at 35 degrees C using the single-microelectrode voltage-clamp technique. 2. Depolarizing voltage steps applied from -100 mV evoked a transient outward current (TOC) from a threshold of -75 mV. From this potential, the amplitude of the current increased non-linearly with voltage. 3. Following its activation TOC reached a peak within 7 ms and subsequently decayed monotonically with a time constant of 30 ms. This time constant did not vary significantly with voltage between -75 and -55 mV. 4. The TOC showed complete steady-state inactivation at potentials positive to -55 mV. Inactivation was removed by hyperpolarization, with a mid-point near -80 mV. The removal of inactivation followed a complex time course with distinct fast (tens of milliseconds) and slow (hundreds of milliseconds) components. 5. Tail current measurements revealed that the TOC equilibrium potential (ETOC) lies near -97 mV in the presence of 3 mM [K+]o. Increasing [K+]o caused a decrease of TOC amplitude and a shift in ETOC of 57 mV/log [K+]o. The TOC is therefore predominantly a K+ current. 6. The TOC was unaffected by tetraethylammonium (up to 12 mM) but was reversibly reduced by 4-aminopyridine (ca. 50% block at 1.0 mM) and dendrotoxin (ca. 50% block at 4 nM). 7. The TOC was strongly inhibited (greater than 70%) by adding Co2+ or Mn2+ (1-3 mM) or Cd2+ (50-400 microM) to Ca-containing solutions, or by removal of Ca2+ from the perfusate. These effects were not accompanied by detectable changes in threshold voltage. The amplitude of TOC was also depressed by the organic Ca2+ channel blocker methoxyverapamil (D600). Finally replacement of Ca2+ by Ba2+ in the perfusate completely and reversibly abolished the TOC. 8. These findings suggest that neurosecretory neurones of the rat supraoptic nucleus display a transient K+ current which is strongly

  13. Transient calcium-dependent potassium current in magnocellular neurosecretory cells of the rat supraoptic nucleus.

    PubMed Central

    Bourque, C W

    1988-01-01

    1. Magnocellular neurosecretory neurones were impaled in the supraoptic nucleus of perfused explants of rat hypothalamus. Membrane currents were studied at 35 degrees C using the single-microelectrode voltage-clamp technique. 2. Depolarizing voltage steps applied from -100 mV evoked a transient outward current (TOC) from a threshold of -75 mV. From this potential, the amplitude of the current increased non-linearly with voltage. 3. Following its activation TOC reached a peak within 7 ms and subsequently decayed monotonically with a time constant of 30 ms. This time constant did not vary significantly with voltage between -75 and -55 mV. 4. The TOC showed complete steady-state inactivation at potentials positive to -55 mV. Inactivation was removed by hyperpolarization, with a mid-point near -80 mV. The removal of inactivation followed a complex time course with distinct fast (tens of milliseconds) and slow (hundreds of milliseconds) components. 5. Tail current measurements revealed that the TOC equilibrium potential (ETOC) lies near -97 mV in the presence of 3 mM [K+]o. Increasing [K+]o caused a decrease of TOC amplitude and a shift in ETOC of 57 mV/log [K+]o. The TOC is therefore predominantly a K+ current. 6. The TOC was unaffected by tetraethylammonium (up to 12 mM) but was reversibly reduced by 4-aminopyridine (ca. 50% block at 1.0 mM) and dendrotoxin (ca. 50% block at 4 nM). 7. The TOC was strongly inhibited (greater than 70%) by adding Co2+ or Mn2+ (1-3 mM) or Cd2+ (50-400 microM) to Ca-containing solutions, or by removal of Ca2+ from the perfusate. These effects were not accompanied by detectable changes in threshold voltage. The amplitude of TOC was also depressed by the organic Ca2+ channel blocker methoxyverapamil (D600). Finally replacement of Ca2+ by Ba2+ in the perfusate completely and reversibly abolished the TOC. 8. These findings suggest that neurosecretory neurones of the rat supraoptic nucleus display a transient K+ current which is strongly

  14. 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

  15. Blockade of median raphe nucleus α1-adrenoceptor subtypes increases food intake in rats.

    PubMed

    da Silva, Eduardo Simão; Flores, Rafael Appel; Cella, Elisa Carolina; Levone, Brunno Rocha; Taschetto, Ana Paula; Kochenborger, Larissa; Terenzi, Mariana Graciela; Faria, Moacir Serralvo; Paschoalini, Marta Aparecida

    2014-09-01

    Previous studies have shown that the blockade of α1-adrenoceptors in the median raphe nucleus (MnR) of free-feeding animals increases food intake. Since there is evidence for the presence of α1A-, α1B- and α1D-adrenoceptors in the MnR of rats, this study investigated the involvement of MnR α1-adrenoceptor subtypes in the control of feeding behavior, looking for possible differences on the role of each α1-adrenoceptor in feeding. Male adult rats weighing 280-300 g with guide cannulae chronically implanted above the MnR were injected with antagonists of α1A- (RS100329, 0, 2, 4 or 20 nmol), α1B- (Rec 15/2615, 0, 2, 4 or 20 nmol) or α1D-adrenoceptor (BMY 7378, 0, 2, 4 or 20 nmol). Subsequently, behavioral evaluation of ingestive and non-ingestive parameters was monitored for 1h and the amount of food and water ingested was assessed for 4h. The highest dose (20 nmol) of RS100329 and BMY 7378 increased food intake, feeding duration and frequency, and decreased the latency to start feeding. During the second hour 2 nmol dose of Rec 15/2615 increased food intake and all doses of BMY 7378 decreased water intake. No behavioral alterations were observed during the fourth hour. The results corroborate previous work from our lab in which we describe the involvement of α1-adrenoceptors of MnR on food intake control. Moreover, we show evidence that α1A- and α1D-adrenoceptors mediate feeding responses to adrenaline injections and that the behavioral modifications are of considerable duration, persisting up to 2h after injection of the antagonists. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Developmental reprogramming of rat GLUT5 requires glucocorticoid receptor translocation to the nucleus

    PubMed Central

    Douard, Véronique; Choi, Hye-In; Elshenawy, Summer; Lagunoff, David; Ferraris, Ronaldo P

    2008-01-01

    Fructose consumption has increased dramatically but little is known about mechanisms regulating the intestinal fructose transporter GLUT5 in vivo. In neonatal rats, GLUT5 can be induced only by luminal fructose and only after 14 days of age, unless the gut is primed with dexamethasone prior to fructose perfusion. To elucidate the mechanisms underlying dexamethasone modulation of GLUT5 development, we first identified the receptor mediating its effects then determined whether those effects were genomic. The glucocorticoid receptor (GR) antagonist RU486 dose-dependently prevented the dexamethasone-mediated effects on body weight, intestinal arginase2 (a known GR-regulated gene) and GLUT5. In contrast, an antagonist of the mineralocorticoid receptor as well as agonists of progesterone (PR) and pregnane-X (PXR) receptors did not block the effects of dexamethasone. These receptor antagonists and agonists had no effect on the intestinal glucose transporter SGLT1. Translocation of the GR into the enterocyte nucleus occurred only in dexamethasone-injected pups perfused with fructose, was accompanied by marked increases in brush border GLUT5 abundance, and was blocked by RU486. A priming duration of ∼24 h is optimal for induction but actinomycin D injection before dexamethasone priming prevented dexamethasone from allowing luminal fructose to induce GLUT5. Actinomycin D had no effect on dexamethasone-independent fructose-induced increases in glucose-6-phosphatase mRNA abundance, suggesting that it did not prevent fructose-induction of GLUT5, but instead prevented dexamethasone-induced synthesis of an intermediate required by fructose for GLUT5 regulation. In suckling rats < 14 days old, developmental regulation of transporters may involve cross-talk between hormonal signals modulating intestinal maturation and nutrient signals regulating specific transporters. PMID:18556366

  17. Endogenous opiates in the nucleus tractus solitarius mediate electroacupuncture-induced sleep activities in rats.

    PubMed

    Cheng, Chiung-Hsiang; Yi, Pei-Lu; Lin, Jaung-Geng; Chang, Fang-Chia

    2011-01-01

    Electroacupuncture (EA) possesses various therapeutic effects, including alleviation of pain, reduction of inflammation and improvement of sleep disturbance. The mechanisms of EA on sleep improvement, however, remain to be determined. It has been stated in ancient Chinese literature that the Anmian (EX17) acupoint is one of the trigger points that alleviates insomnia. We previously demonstrated that EA stimulation of Anmian acupoints in rats during the dark period enhances non-rapid eye movement (NREM) sleep, which involves the induction of cholinergic activity in the nucleus tractus solitarius (NTS). In addition to cholinergic activation of the NTS, activation of the endogenous opioidergic system may also be a mechanism by which acupuncture affects sleep. Therefore, this study was designed to investigate the involvement of the NTS opioidergic system in EA-induced alterations in sleep. Our present results indicate that EA of Anmian acupoints increased NREM sleep, but not rapid eye movement sleep, during the dark period in rats. This enhancement in NREM sleep was dose-dependently blocked by microinjection of opioid receptor antagonist, naloxone, and the μ-opioid receptor antagonist, naloxonazine, into the NTS; administrations of δ-receptor antagonist, natrindole, and the κ-receptor antagonist, nor-binaltrophimine, however, did not affect EA-induced alterations in sleep. Furthermore, β-endorphin was significantly increased in both the brainstem and hippocampus after the EA stimuli, an effect blocked by administration of the muscarinic antagonist scopolamine into the NTS. Our findings suggest that mechanisms of EA-induced NREM sleep enhancement may be mediated, in part, by cholinergic activation, stimulation of the opiodergic neurons to increase the concentrations of β-endorphin and the involvement of the μ-opioid receptors.

  18. Overexpression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats.

    PubMed

    Larson, Erin B; Graham, Danielle L; Arzaga, Rose R; Buzin, Nicole; Webb, Joseph; Green, Thomas A; Bass, Caroline E; Neve, Rachael L; Terwilliger, Ernest F; Nestler, Eric J; Self, David W

    2011-11-09

    Chronic exposure to addictive drugs enhances cAMP response element binding protein (CREB)-regulated gene expression in nucleus accumbens (NAc), and these effects are thought to reduce the positive hedonic effects of passive cocaine administration. Here, we used viral-mediated gene transfer to produce short- and long-term regulation of CREB activity in NAc shell of rats engaging in volitional cocaine self-administration. Increasing CREB expression in NAc shell markedly enhanced cocaine reinforcement of self-administration behavior, as indicated by leftward (long-term) and upward (short-term) shifts in fixed ratio dose-response curves. CREB also increased the effort exerted by rats to obtain cocaine on more demanding progressive ratio schedules, an effect highly correlated with viral-induced modulation of BDNF protein in the NAc shell. CREB enhanced cocaine reinforcement when expressed either throughout acquisition of self-administration or when expression was limited to postacquisition tests, indicating a direct effect of CREB independent of reinforcement-related learning. Downregulating endogenous CREB in NAc shell by expressing a short hairpin RNA reduced cocaine reinforcement in similar tests, while overexpression of a dominant-negative CREB(S133A) mutant had no significant effect on cocaine self-administration. Finally, increasing CREB expression after withdrawal from self-administration enhanced cocaine-primed relapse, while reducing CREB levels facilitated extinction of cocaine seeking, but neither altered relapse induced by cocaine cues or footshock stress. Together, these findings indicate that CREB activity in NAc shell increases the motivation for cocaine during active self-administration or after withdrawal from cocaine. Our results also highlight that volitional and passive drug administration can lead to substantially different behavioral outcomes.

  19. GABAA-receptor activation in the subthalamic nucleus compensates behavioral asymmetries in the hemiparkinsonian rat.

    PubMed

    Petri, David; Pum, Martin; Vesper, Jan; Huston, Joseph P; Schnitzler, Alfons

    2013-09-01

    The subthalamic nucleus (STN) has a pivotal role in the pathophysiology of Parkinson's disease (PD). Modulation of STN activity (by lesions, pharmacological or electrical stimulation) has been shown to improve motor parameters in PD patients and in animal models of PD. In an attempt to characterize the neurochemical bases for such antiparkinsonian action, we address specific neurotransmitter systems via local pharmacological manipulation of the STN in hemiparkinsonian rats. Here, we have focused on the GABAergic and glutamatergic receptors in the STN. In animals with unilateral 6-hydroxydopamine lesions of the nigro-striatal tract, we administered either the selective GABAA-agonist muscimol (0.5 μg and 1.0 μg), the non-competitive N-methyl-d-aspartate (NMDA)-antagonist MK-801 (dizocilpine; 2.5 μg), or vehicle (0.25 μl) into the STN. The effects of GABAergic and glutamatergic modulation of the STN on motor parameters were assessed by gauging rotational behavior and locomotion. Application of muscimol ipsilateral to the side of dopamine-depletion influenced turning behavior in a dose-dependent fashion, with the low dose re-adjusting turning behavior to a non-biased distribution, and the high dose evoking contraversive turning. The administration of MK-801 did not have such effects. These findings give evidence for the involvement of GABAergic activation in the STN in the compensation of motor asymmetries in the hemiparkinsonian rat, whereas N-methyl-d-aspartate (NMDA)-antagonism was ineffective in this model of PD.

  20. Deep brain stimulation of the subthalamic nucleus increases premature responding in a rat gambling task.

    PubMed

    Aleksandrova, Lily R; Creed, Meaghan C; Fletcher, Paul J; Lobo, Daniela S S; Hamani, Clement; Nobrega, José N

    2013-05-15

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option for the motor symptoms of Parkinson's disease (PD). However, several recent studies have found an association between STN-DBS and increased impulsivity. Currently, it is not clear whether the observed increase in impulsivity results from STN-DBS per se, or whether it involves an interaction with the underlying PD neuropathology and/or intake of dopaminergic drugs. We investigated the effects of STN-DBS on performance of intact rats on two tasks measuring impulsive responding: a novel rat gambling task (rGT) and a differential reinforcement of low rate responding (DRL20s) schedule. Following initial behavioural training, animals received electrode implantation into the STN (n=24) or sham surgery (n=24), and were re-tested on their assigned behavioural task, with or without STN-DBS. Bilateral STN-DBS administered for two hours immediately prior to testing, had no effects on rGT choice behaviour or on DRL response inhibition (p>0.05). However, STN-DBS significantly increased premature responding in the rGT task (p=0.0004), an effect that took several sessions to develop and persisted in subsequent trials when no stimulation was given. Consistent with the notion of distinct facets of impulsivity with unique neurochemical underpinnings, we observed differential effects of STN-DBS in the two tasks employed. These results suggest that STN-DBS in the absence of parkinsonism may not lead to a general loss of inhibitory control, but may instead affect impulsivity under specific conditions.

  1. Plasticity of GABAA receptor-mediated neurotransmission in the nucleus accumbens of alcohol-dependent rats

    PubMed Central

    Liang, Jing; Lindemeyer, A. Kerstin; Suryanarayanan, Asha; Meyer, Edward M.; Marty, Vincent N.; Ahmad, S. Omar; Shao, Xuesi Max; Olsen, Richard W.

    2014-01-01

    Chronic alcohol exposure-induced changes in reinforcement mechanisms and motivational state are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Here we describe the long-lasting alterations of γ-aminobutyric acid type A receptors (GABAARs) of medium spiny neurons (MSNs) in the NAcc after chronic intermittent ethanol (CIE) treatment, a rat model of alcohol dependence. CIE treatment and withdrawal (>40 days) produced decreases in the ethanol and Ro15-4513 potentiation of extrasynaptic GABAARs, which mediate the picrotoxin-sensitive tonic current (Itonic), while potentiation of synaptic receptors, which give rise to miniature inhibitory postsynaptic currents (mIPSCs), was increased. Diazepam sensitivity of both Itonic and mIPSCs was decreased by CIE treatment. The average magnitude of Itonic was unchanged, but mIPSC amplitude and frequency decreased and mIPSC rise time increased after CIE treatment. Rise-time histograms revealed decreased frequency of fast-rising mIPSCs after CIE treatment, consistent with possible decreases in somatic GABAergic synapses in MSNs from CIE rats. However, unbiased stereological analysis of NeuN-stained NAcc neurons did not detect any decreases in NAcc volume, neuronal numbers, or neuronal cell body volume. Western blot analysis of surface subunit levels revealed selective decreases in α1 and δ and increases in α4, α5, and γ2 GABAAR subunits after CIE treatment and withdrawal. Similar, but reversible, alterations occurred after a single ethanol dose (5 g/kg). These data reveal CIE-induced long-lasting neuroadaptations in the NAcc GABAergic neurotransmission. PMID:24694935

  2. Systemic administration of resveratrol suppress the nociceptive neuronal activity of spinal trigeminal nucleus caudalis in rats.

    PubMed

    Takehana, Shiori; Sekiguchi, Kenta; Inoue, Maki; Kubota, Yoshiko; Ito, Yukihiko; Yui, Kei; Shimazu, Yoshihito; Takeda, Mamoru

    2016-01-01

    Although a modulatory role has been reported for the red wine polyphenol resveratrol on several types of ion channels and excitatory synaptic transmission in the nervous system, the acute effects of resveratrol in vivo, particularly on nociceptive transmission of the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous resveratrol administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 18 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was inhibited by resveratrol (0.5-2 mg/kg, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. These inhibitory effects were reversed after approximately 20 min. The relative magnitude of inhibition by resveratrol of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. These results suggest that, in the absence of inflammatory or neuropathic pain, acute intravenous resveratrol administration suppresses trigeminal sensory transmission, including nociception, and so resveratrol may be used as a complementary and alternative medicine therapeutic agent for the treatment of trigeminal nociceptive pain, including hyperalgesia.

  3. Intracellular Calcium Spikes in Rat Suprachiasmatic Nucleus Neurons Induced by BAPTA-Based Calcium Dyes

    PubMed Central

    Hong, Jin Hee; Min, Cheol Hong; Jeong, Byeongha; Kojiya, Tomoyoshi; Morioka, Eri; Nagai, Takeharu; Ikeda, Masayuki; Lee, Kyoung J.

    2010-01-01

    Background Circadian rhythms in spontaneous action potential (AP) firing frequencies and in cytosolic free calcium concentrations have been reported for mammalian circadian pacemaker neurons located within the hypothalamic suprachiasmatic nucleus (SCN). Also reported is the existence of “Ca2+ spikes” (i.e., [Ca2+]c transients having a bandwidth of 10∼100 seconds) in SCN neurons, but it is unclear if these SCN Ca2+ spikes are related to the slow circadian rhythms. Methodology/Principal Findings We addressed this issue based on a Ca2+ indicator dye (fluo-4) and a protein Ca2+ sensor (yellow cameleon). Using fluo-4 AM dye, we found spontaneous Ca2+ spikes in 18% of rat SCN cells in acute brain slices, but the Ca2+ spiking frequencies showed no day/night variation. We repeated the same experiments with rat (and mouse) SCN slice cultures that expressed yellow cameleon genes for a number of different circadian phases and, surprisingly, spontaneous Ca2+ spike was barely observed (<3%). When fluo-4 AM or BAPTA-AM was loaded in addition to the cameleon-expressing SCN cultures, however, the number of cells exhibiting Ca2+ spikes was increased to 13∼14%. Conclusions/Significance Despite our extensive set of experiments, no evidence of a circadian rhythm was found in the spontaneous Ca2+ spiking activity of SCN. Furthermore, our study strongly suggests that the spontaneous Ca2+ spiking activity is caused by the Ca2+ chelating effect of the BAPTA-based fluo-4 dye. Therefore, this induced activity seems irrelevant to the intrinsic circadian rhythm of [Ca2+]c in SCN neurons. The problems with BAPTA based dyes are widely known and our study provides a clear case for concern, in particular, for SCN Ca2+ spikes. On the other hand, our study neither invalidates the use of these dyes as a whole, nor undermines the potential role of SCN Ca2+ spikes in the function of SCN. PMID:20224788

  4. Intracellular calcium spikes in rat suprachiasmatic nucleus neurons induced by BAPTA-based calcium dyes.

    PubMed

    Hong, Jin Hee; Min, Cheol Hong; Jeong, Byeongha; Kojiya, Tomoyoshi; Morioka, Eri; Nagai, Takeharu; Ikeda, Masayuki; Lee, Kyoung J

    2010-03-10

    Circadian rhythms in spontaneous action potential (AP) firing frequencies and in cytosolic free calcium concentrations have been reported for mammalian circadian pacemaker neurons located within the hypothalamic suprachiasmatic nucleus (SCN). Also reported is the existence of "Ca(2+) spikes" (i.e., [Ca(2+)](c) transients having a bandwidth of 10 approximately 100 seconds) in SCN neurons, but it is unclear if these SCN Ca(2+) spikes are related to the slow circadian rhythms. We addressed this issue based on a Ca(2+) indicator dye (fluo-4) and a protein Ca(2+) sensor (yellow cameleon). Using fluo-4 AM dye, we found spontaneous Ca(2+) spikes in 18% of rat SCN cells in acute brain slices, but the Ca(2+) spiking frequencies showed no day/night variation. We repeated the same experiments with rat (and mouse) SCN slice cultures that expressed yellow cameleon genes for a number of different circadian phases and, surprisingly, spontaneous Ca(2+) spike was barely observed (<3%). When fluo-4 AM or BAPTA-AM was loaded in addition to the cameleon-expressing SCN cultures, however, the number of cells exhibiting Ca(2+) spikes was increased to 13 approximately 14%. Despite our extensive set of experiments, no evidence of a circadian rhythm was found in the spontaneous Ca(2+) spiking activity of SCN. Furthermore, our study strongly suggests that the spontaneous Ca(2+) spiking activity is caused by the Ca(2+) chelating effect of the BAPTA-based fluo-4 dye. Therefore, this induced activity seems irrelevant to the intrinsic circadian rhythm of [Ca(2+)](c) in SCN neurons. The problems with BAPTA based dyes are widely known and our study provides a clear case for concern, in particular, for SCN Ca(2+) spikes. On the other hand, our study neither invalidates the use of these dyes as a whole, nor undermines the potential role of SCN Ca(2+) spikes in the function of SCN.

  5. Endogenous Opiates in the Nucleus Tractus Solitarius Mediate Electroacupuncture-Induced Sleep Activities in Rats

    PubMed Central

    Cheng, Chiung-Hsiang; Yi, Pei-Lu; Lin, Jaung-Geng; Chang, Fang-Chia

    2011-01-01

    Electroacupuncture (EA) possesses various therapeutic effects, including alleviation of pain, reduction of inflammation and improvement of sleep disturbance. The mechanisms of EA on sleep improvement, however, remain to be determined. It has been stated in ancient Chinese literature that the Anmian (EX17) acupoint is one of the trigger points that alleviates insomnia. We previously demonstrated that EA stimulation of Anmian acupoints in rats during the dark period enhances non-rapid eye movement (NREM) sleep, which involves the induction of cholinergic activity in the nucleus tractus solitarius (NTS). In addition to cholinergic activation of the NTS, activation of the endogenous opioidergic system may also be a mechanism by which acupuncture affects sleep. Therefore, this study was designed to investigate the involvement of the NTS opioidergic system in EA-induced alterations in sleep. Our present results indicate that EA of Anmian acupoints increased NREM sleep, but not rapid eye movement sleep, during the dark period in rats. This enhancement in NREM sleep was dose-dependently blocked by microinjection of opioid receptor antagonist, naloxone, and the μ-opioid receptor antagonist, naloxonazine, into the NTS; administrations of δ-receptor antagonist, natrindole, and the κ-receptor antagonist, nor-binaltrophimine, however, did not affect EA-induced alterations in sleep. Furthermore, β-endorphin was significantly increased in both the brainstem and hippocampus after the EA stimuli, an effect blocked by administration of the muscarinic antagonist scopolamine into the NTS. Our findings suggest that mechanisms of EA-induced NREM sleep enhancement may be mediated, in part, by cholinergic activation, stimulation of the opiodergic neurons to increase the concentrations of β-endorphin and the involvement of the μ-opioid receptors. PMID:19729491

  6. Ionic basis of the caesium-induced depolarisation in rat supraoptic nucleus neurones

    PubMed Central

    Ghamari-Langroudi, Masoud; Bourque, Charles W

    2001-01-01

    The effects of external Cs+ on magnocellular neurosecretory cells were studied during intracellular recordings from 93 supraoptic nucleus neurones in superfused explants of rat hypothalamus.Bath application of 3–5 mm Cs+ provoked reversible membrane depolarisation and increased firing rate in all of the neurones tested. Voltage-current analysis revealed an increase in membrane resistance between −120 and −55 mV. The increase in resistance was greater below −85 mV than at more positive potentials.Voltage-clamp analysis showed that external Cs+ blocked the hyperpolarisation-activated inward current, IH. Under current clamp, application of ZD 7288, a selective blocker of IH, caused an increase in membrane resistance at voltages ≤−65 mV. Voltage-current analysis further revealed that blockade of IH caused hyperpolarisation when the initial voltage was < −60 mV but had no effect at more positive values.Current- and voltage-clamp analysis of the effects of Cs+ in the presence of ZD 7288, or ZD 7288 and tetraethyl ammonium (TEA), revealed an increase in membrane resistance throughout the range of voltages tested (−120 to −45 mV). The current blocked by Cs+ in the absence of IH was essentially voltage independent and reversed at −100 mV. The reversal potential shifted by +22.7 mV when external [K+] was increased from 3 to 9 mm. We conclude that, in addition to blocking IH, external Cs+ blocks a leakage K+ current that contributes significantly to the resting potential of rat magnocellular neurosecretory cells. PMID:11691873

  7. Changes in immunoreactivity to calcium-binding proteins in the anterior olfactory nucleus of the rat after neonatal olfactory deprivation.

    PubMed

    Barbado, M V; Briñón, J G; Weruaga, E; Porteros, A; Arévalo, R; Aijón, J; Alonso, J R

    2002-09-01

    The effects of olfactory deprivation on the density of neuronal populations expressing the calcium-binding proteins calbindin D-28k, calretinin, and parvalbumin in the anterior olfactory nucleus of the rat were studied immunohistochemically in 60-day-old rats subjected to unilateral naris closure on the day of birth. The neuronal populations were characterized morphologically and topologically, and the density of each cell type was calculated in each subdivision of the anterior olfactory nucleus at seven rostrocaudal levels. Data were gathered into three groups: data from either the ipsilateral or contralateral anterior olfactory nucleus of experimental animals and data from control animals. Statistical analysis indicated that disruption of the normal afferent activity to one olfactory bulb affects the expression of the calcium-binding proteins investigated in the anterior olfactory nucleus, as revealed by variations in the density of certain neuronal populations. The observed effects were very heterogeneous and could not be related to any specific neuronal type, location, or to the expression of a given calcium-binding protein. Nevertheless, as a general rule the most affected neuronal populations were those expressing calbindin D-28k located in the rostral subdivisions. These subdivisions are the latest to develop in mammals and are those that receive the largest amount of inputs from the olfactory bulb.

  8. Presence and distribution of three calcium binding proteins in projection neurons of the adult rat cochlear nucleus.

    PubMed

    Pór, Agnes; Pocsai, Krisztina; Rusznák, Zoltán; Szucs, Géza

    2005-03-28

    The presence and distribution of three cytoplasmic calcium binding proteins, calbindin, calretinin, and parvalbumin, have been investigated in the projection neurons of the cochlear nucleus complex in adult rats by using immunohistochemistry in free-floating slices. Identification of the individual cell types was carried out on the basis of their intranuclear localization, morphological characteristics, and (in the cases of pyramidal and bushy neurons) by retrograde labeling with rhodamine-dextran. The most important findings were confirmed by using confocal microscopy. The data obtained in these experiments are the first to demonstrate the presence of parvalbumin in pyramidal neurons and globular and spherical bushy cells of rat cochlear nucleus, whereas octopus and giant cells did not show positivity for parvalbumin. Calretinin was not present in either Purkinje-like cells or giant neurons. According to the double immunolabeling co-localization experiments, the pyramidal neurons, Purkinje-like cells, globular bushy cells, and octopus cells express two different calcium binding proteins in their cytoplasm (although in different combinations) whereas giant cells and spherical bushy cells contain solely calbindin and parvalbumin, respectively. The presence of calretinin in globular bushy cells provides a tool for distinguishing them from spherical bushy cells. The immunolabeling of the fibers and axonal endings of the acoustic nerve in the ventral part of the cochlear nucleus indicated that these structures are also parvalbumin positive. It is concluded that the heterogenous cell composition of the cochlear nucleus is accompanied by a rather complex expression pattern of the cytoplasmic calcium binding proteins.

  9. Differential sensitivity of ethanol-elicited ERK phosphorylation in nucleus accumbens of Sardinian alcohol-preferring and -non preferring rats.

    PubMed

    Rosas, Michela; Zaru, Alessandro; Sabariego, Marta; Giugliano, Valentina; Carboni, Ezio; Colombo, Giancarlo; Acquas, Elio

    2014-08-01

    Sardinian alcohol-preferring (sP) and -non preferring (sNP) rats have been selectively bred for opposite ethanol preference and consumption; sP rats represent a validated experimental tool to model several aspects of excessive ethanol drinking in humans. Phosphorylated Extracellular signal-Regulated Kinase (pERK) in dopamine-rich terminal areas plays a critical role in several psychopharmacological effects of addictive drugs, including ethanol. This study was aimed at investigating whether ethanol-elicited ERK activation may differ in key brain areas of ethanol-naïve sP and sNP rats. To this end, the effects of ethanol (0, 0.5, 1, and 2 g/kg, administered intra-gastrically [i.g.]) on ERK phosphorylation were assessed by pERK immunohistochemistry in the shell (AcbSh) and core (AcbC) of the nucleus accumbens (Acb) as well as in the prelimbic (PrL) and infralimbic (IL) prefrontal cortex (PFCx), in the bed nucleus of stria terminalis (BSTL) and in the central nucleus of the amygdala (CeA). Ethanol (1 g/kg) significantly increased pERK immunoreactivity in AcbSh and AcbC of sP but not sNP rats. Conversely, ethanol failed to affect pERK expression in PrL and IL PFCx as well as in BSTL and CeA of both sP and sNP rats. These results suggest that selective breeding of these rat lines results in differential effects of acute ethanol on ERK phosphorylation in brain regions critical for the psychopharmacological effects of ethanol.

  10. 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

  11. Substance P and neurokinin A variations throughout the rat estrous cycle; comparison with ovariectomized and male rats: II. Trigeminal nucleus and cervical spinal cord.

    PubMed

    Duval, P; Lenoir, V; Moussaoui, S; Garret, C; Kerdelhué, B

    1996-09-01

    Substance P and neurokinin A were assayed in the trigeminal nucleus and cervical spinal cord of 4-day cycling female, ovariectomized, and male rats. During the estrous cycle, levels were largely stable in the trigeminal nucleus. In ovariectomized rats, the levels differed from those on any day of the estrous cycle suggesting a weak effect of ovarian steroids. In males, the variations in the substance P and neurokinin A contents in the trigeminal nucleus were not similar to those in either cyclic or ovariectomized rats. The levels fluctuated substantially in the cervical spinal cord. During the first 3 days of the estrous cycle, the substance P and neurokinin A contents fell concomitant with the 17 beta-estradiol surge, suggesting a downregulation of substance P and neurokinin A contents by 17 beta-estradiol. Furthermore, on estrus, progesterone seemed to inhibit the accumulation of both neurokinins. Testosterone may stimulate accumulation of substance P and neurokinin A in the cervical spinal cord, with a marked circadian rhythm. These results are in favor of the neurokinin content of the spinal cord being regulated by the gonadal steroids. In the trigeminal nucleus, only testosterone has an effect.

  12. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats.

    PubMed

    Baum, S S; Hill, R; Rommelspacher, H

    1998-10-01

    1. Kavapyrones have well-known psychotropic properties. The most common actions of the extract are relaxation and euphoria, depending on the circumstances of ingestion, whereas higher doses cause sleepiness and skeletal muscle relaxation. Several other actions have been reported such as anticonvulsant properties, neuroprotection and analgesia. No interactions with neuroreceptors have yet been found that would explain the multiple actions. 2. To reveal neuronal functions affected by the kavapyrones the authors studied their actions on the mesolimbic reward system using in vivo microdialysis. 3. A small dose of kava extract (20 mg/kg body weight i.p.) caused changes in rat behaviour and concentrations of dopamine in the nucleus accumbens. Higher doses (120 mg/kg i.p.) increased the levels of dopamine. With respect to the individual compounds, D,L-kawain induced in low doses a decrease in dopamine levels and in higher amounts either an increase or no change in dopamine concentrations. Yangonin resulted in a decrease of dopamine levels to below the detection limit and desmethoxyyangonin in an increase of dopamine levels. Dihydrokawain, methysticin and dihydromethysticin did not produce any significant changes of dopamine levels. D,L-kawain caused a decrease in 5-HT concentrations. Some of the other kavapyrones affected 5-HT levels as well. 4. The results suggest that the relaxing and slightly euphoric actions may be caused by the activation of the mesolimbic dopaminergic neurones. Changes of the activity of 5-HT neurones could explain the sleep-inducing action.

  13. Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat.

    PubMed

    Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Chávez-Saldaña, Margarita; Rojas, Patricia; Gutiérrez-Pérez, Oscar; Rojas, Carolina; Arteaga-Silva, Marcela

    2016-02-01

    Neonatal exposure to monosodium glutamate (MSG) induces circadian disorders in several physiological and behavioural processes regulated by the suprachiasmatic nucleus (SCN). The objective of this study was to evaluate the effects of neonatal exposure to MSG on locomotor activity, and on morphology, cellular density and expression of proteins, as evaluated by optical density (OD), of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)- and glial fibrillary acidic protein (GFAP)-immunoreactive cells in the SCN. Male Wistar rats were used: the MSG group was subcutaneously treated from 3 to 10 days of age with 3.5 mg/g/day. Locomotor activity was evaluated at 90 days of age using 'open-field' test, and the brains were processed for immunohistochemical studies. MSG exposure induced a significant decrease in locomotor activity. VP- and VIP-immunoreactive neuronal densities showed a significant decrease, while the somatic OD showed an increase. Major axes and somatic area were significantly increased in VIP neurons. The cellular and optical densities of GFAP-immunoreactive sections of SCN were significantly increased. These results demonstrated that newborn exposure to MSG induced morphological alterations in SCN cells, an alteration that could be the basis for behavioural disorders observed in the animals.

  14. Sensorimotor Processing in the Newborn Rat Red Nucleus during Active Sleep

    PubMed Central

    Del Rio-Bermudez, Carlos; Sokoloff, Greta

    2015-01-01

    Sensory feedback from sleep-related myoclonic twitches is thought to drive activity-dependent development in spinal cord and brain. However, little is known about the neural pathways involved in the generation of twitches early in development. The red nucleus (RN), source of the rubrospinal tract, has been implicated in the production of phasic motor activity during active sleep in adults. Here we hypothesized that the RN is also a major source of motor output for twitching in early infancy, a period when twitching is an especially abundant motor behavior. We recorded extracellular neural activity in the RN during sleep and wakefulness in 1-week-old unanesthetized rats. Neurons in the RN fired phasically before twitching and wake movements of the contralateral forelimb. A subpopulation of neurons in the RN exhibited a significant peak of activity after forelimb movement onset, suggesting reafferent sensory processing. Consistent with this observation, manual stimulation of the forelimb evoked RN responses. Unilateral inactivation of the RN using a mixture comprising GABAA, GABAB, and glycine receptor agonists caused an immediate and temporary increase in motor activity followed by a marked and prolonged decrease in twitching and wake movements. Altogether, these data support a causal role for the RN in infant motor behavior. Furthermore, they indicate that twitching, which is characterized by discrete motor output and reafferent input, provides an opportunity for sensorimotor integration and activity-dependent development of topography within the newborn RN. PMID:26019345

  15. Orexins excite neurons of the rat cerebellar nucleus interpositus via orexin 2 receptors in vitro.

    PubMed

    Yu, Lei; Zhang, Xiao-Yang; Zhang, Jun; Zhu, Jing-Ning; Wang, Jian-Jun

    2010-03-01

    Orexins are newfound hypothalamic neuropeptides implicated in the regulation of feeding behavior, sleep-wakefulness cycle, nociception, addiction, emotions, as well as narcolepsy. However, little is known about roles of orexins in motor control. Therefore, the present study was designed to investigate the effect of orexins on neuronal activity in the cerebellum, an important subcortical center for motor control. In this study, perfusing slices with orexin A (100 nM-1 microM) or orexin B (100 nM-1 microM) both produced neurons in the rat cerebellar interpositus nucleus (IN) a concentration-dependent excitatory response (96/143, 67.1%). Furthermore, both of the excitations induced by orexin A and B were not blocked by the low-Ca(2+)/high-Mg(2+) medium (n = 8), supporting a direct postsynaptic action of the peptides. Highly selective orexin 1 receptor antagonist SB-334867 did not block the excitatory response of cerebellar IN neurons to orexins (n = 22), but [Ala(11), D-Leu(15)] orexin B, a highly selective orexin 2 receptor (OX(2)R) agonist, mimicked the excitatory effect of orexins on the cerebellar neurons (n = 18). These results demonstrate that orexins excite the cerebellar IN neurons through OX(2)R and suggest that the central orexinergic nervous system may actively participate in motor control through its modulation on one of the final outputs of the spinocerebellum.

  16. Allyl isothiocyanates and cinnamaldehyde potentiate miniature excitatory postsynaptic inputs in the supraoptic nucleus in rats.

    PubMed

    Yokoyama, Toru; Ohbuchi, Toyoaki; Saito, Takeshi; Sudo, Yuka; Fujihara, Hiroaki; Minami, Kouichiro; Nagatomo, Toshihisa; Uezono, Yasuhito; Ueta, Yoichi

    2011-03-25

    Allyl isothiocyanates (AITC) and cinnamaldehyde are pungent compounds present in mustard oil and cinnamon oil, respectively. These compounds are well known as transient receptor potential ankyrin 1 (TRPA1) agonists. TRPA1 is activated by low temperature stimuli, mechanosensation and pungent irritants such as AITC and cinnamaldehyde. TRPA1 is often co-expressed in TRPV1. Recent study showed that hypertonic solution activated TRPA1 as well as TRPV1. TRPV1 is involved in excitatory synaptic inputs to the magnocellular neurosecretory cells (MNCs) that produce vasopressin in the supraoptic nucleus (SON). However, it remains unclear whether TRPA1 may be involved in this activation. In the present study, we examined the role of TRPA1 on the synaptic inputs to the MNCs in in vitro rat brain slice preparations, using whole-cell patch-clamp recordings. In the presence of tetrodotoxin, AITC (50μM) and cinnamaldehyde (30μM) increased the frequency of miniature excitatory postsynaptic currents without affecting the amplitude. This effect was significantly attenuated by previous exposure to ruthenium red (10μM), non-specific TRP channels blocker, high concentration of menthol (300μM) and HC-030031 (10μM), which are known to antagonize the effects of TRPA1 agonists. These results suggest that TRPA1 may exist at presynaptic terminals to the MNCs and enhance glutamate release in the SON.

  17. Role of cuneiform nucleus in regulation of sympathetic vasomotor tone in rats.

    PubMed

    Shafei, Mohammad Naser; Nasimi, Ali; Alaei, Hojatallah; Pourshanazari, Ali Asghar; Hosseini, Mahmoud

    2012-06-01

    The cuneiform nucleus (CnF) is a sympathoexcitatory area involved in the central cardiovascular regulation. Its role in the maintaining vasomotor tone has, however, not yet been clarified. In the present study the effects of cobalt chloride (CoCl(2)) a nonselective synapse blocker and NMDA and non-NMDA glutamate receptors on resting mean arterial blood pressure and heart rate of CnF have been evaluated. CoCl(2), AP5 (an NMDA receptor antagonist) and CNQX (an AMPA/kinase receptor antagonist) (100nl) were microinjected into the CnF of anesthetized rats. The blood pressure and heart rate were recorded throughout the experiment. The responses of blood pressure and heart rate were compared with the pre-injection (paired t-test) and control (independent t-test) values. Microinjection of CoCl(2), AP5 and CNQX did not change the basal blood pressure and heart rate. In conclusion, our present study indicates that the CnF is not important in the regulation of cardiovascular tone. Copyright © 2011. Published by Elsevier Ireland Ltd.

  18. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

    PubMed Central

    Albaugh, Daniel L.; Salzwedel, Andrew; Van Den Berge, Nathalie; Gao, Wei; Stuber, Garret D.; Shih, Yen-Yu Ian

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  19. Light-Induced Responses of Slow Oscillatory Neurons of the Rat Olivary Pretectal Nucleus

    PubMed Central

    Szkudlarek, Hanna J.; Orlowska, Patrycja; Lewandowski, Marian H.

    2012-01-01

    Background The olivary pretectal nucleus (OPN) is a small midbrain structure responsible for pupil constriction in response to eye illumination. Previous electrophysiological studies have shown that OPN neurons code light intensity levels and therefore are called luminance detectors. Recently, we described an additional population of OPN neurons, characterized by a slow rhythmic pattern of action potentials in light-on conditions. Rhythmic patterns generated by these cells last for a period of approximately 2 minutes. Methodology To answer whether oscillatory OPN cells are light responsive and whether oscillatory activity depends on retinal afferents, we performed in vivo electrophysiology experiments on urethane anaesthetized Wistar rats. Extracellular recordings were combined with changes in light conditions (light-dark-light transitions), brief light stimulations of the contralateral eye (diverse illuminances) or intraocular injections of tetrodotoxin (TTX). Conclusions We found that oscillatory neurons were able to fire rhythmically in darkness and were responsive to eye illumination in a manner resembling that of luminance detectors. Their firing rate increased together with the strength of the light stimulation. In addition, during the train of light pulses, we observed two profiles of responses: oscillation-preserving and oscillation-disrupting, which occurred during low- and high-illuminance stimuli presentation respectively. Moreover, we have shown that contralateral retina inactivation eliminated oscillation and significantly reduced the firing rate of oscillatory cells. These results suggest that contralateral retinal innervation is crucial for the generation of an oscillatory pattern in addition to its role in driving responses to visual stimuli. PMID:22427957

  20. Activation of 5-hyrdoxytryptamine 7 receptors within the rat nucleus tractus solitarii modulates synaptic properties

    PubMed Central

    Matott, Michael P.; Kline, David D.

    2016-01-01

    Serotonin (5-HT) is a potent neuromodulator with multiple receptor types within the cardiorespiratory system, including the nucleus tractus solitarii (nTS) - the central termination site of visceral afferent fibers. The 5-HT7 receptor facilitates cardiorespiratory reflexes through its action in the brainstem and likely in the nTS. However, the mechanism and site of action for these effects is not clear. In this study, we examined the expression and function of 5-HT7 receptors in the nTS of Sprague-Dawley rats. 5-HT7 receptor mRNA and protein were identified across the rostrocaudal extent of the nTS. To determine 5-HT7 receptor function, we examined nTS synaptic properties following 5-HT7 receptor activation in monosynaptic nTS neurons in the in vitro brainstem slice preparation. Application of 5-HT7 receptor agonists altered tractus solitarii evoked and spontaneous excitatory postsynaptic currents which were attenuated with a selective 5-HT7 receptor antagonist. 5-HT7 receptor-mediated changes in excitatory postsynaptic currents were also altered by block of 5-HT1A and GABAA receptors. Interestingly, 5-HT7 receptor activation also reduced the amplitude but not frequency of GABAA-mediated inhibitory currents. Together these results indicate a complex role for 5-HT7 receptors in the nTS that mediate its diverse effects on cardiorespiratory parameters. PMID:26779891

  1. Activation of MT(2) melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock.

    PubMed

    Hunt, A E; Al-Ghoul, W M; Gillette, M U; Dubocovich, M L

    2001-01-01

    The aim of this study was to identify the melatonin receptor type(s) (MT(1) or MT(2)) mediating circadian clock resetting by melatonin in the mammalian suprachiasmatic nucleus (SCN). Quantitative receptor autoradiography with 2-[(125)I]iodomelatonin and in situ hybridization histochemistry, with either (33)P- or digoxigenin-labeled antisense MT(1) and MT(2) melatonin receptor mRNA oligonucleotide probes, revealed specific expression of both melatonin receptor types in the SCN of inbred Long-Evans rats. The melatonin receptor type mediating phase advances of the circadian rhythm of neuronal firing rate in the SCN slice was assessed using competitive melatonin receptor antagonists, the MT(1)/MT(2) nonselective luzindole and the MT(2)-selective 4-phenyl-2-propionamidotetraline (4P-PDOT). Luzindole and 4P-PDOT (1 nM-1 microM) did not affect circadian phase on their own; however, they blocked both the phase advances (approximately 4 h) in the neuronal firing rate induced by melatonin (3 pM) at temporally distinct times of day [i.e., subjective dusk, circadian time (CT) 10; and dawn, CT 23], as well as the associated increases in protein kinase C activity. We conclude that melatonin mediates phase advances of the SCN circadian clock at both dusk and dawn via activation of MT(2) melatonin receptor signaling.

  2. Cardiovascular effects of injections of vasopressin into the nucleus tractus solitarius in conscious rats.

    PubMed Central

    King, K. A.; Pang, C. C.

    1987-01-01

    The effects of injections of arginine vasopressin (AVP) into the nucleus tractus solitarius (NTS) on mean arterial pressure (MAP), heart rate (HR) and plasma concentrations of noradrenaline and adrenaline were investigated in conscious, unrestrained rats. Injection of 2 ng AVP into the NTS significantly increased MAP but not plasma catecholamine concentrations, while injection of 10 ng AVP significantly increased MAP and plasma noradrenaline and adrenaline levels. Neither dose of AVP produced any change in HR. The vehicle did not affect MAP, HR or plasma catecholamine levels. Injection of a specific pressor antagonist of AVP, d(CH2)5Tyr-(Me)AVP (10 ng), did not change MAP, HR or plasma noradrenaline or adrenaline levels. These results suggest that the NTS is a central site of the pressor action of AVP. However, since the injection of the AVP antagonist did not reduce MAP or plasma noradrenaline or adrenaline levels, it suggests that AVP does not act tonically at the NTS to influence sympathoadrenal outflow. PMID:3567458

  3. Neuron types in the rat dorsal lateral geniculate nucleus identified in Nissl and deimpregnated Golgi preparations.

    PubMed

    Werner, L; Brauer, K

    1984-01-01

    To identify geniculo-cortical relay neurons (GCR-neurons) and interneurons (I-neurons) in Nissl stained sections of the albino rat's (Wistar strain) dorsal lateral geniculate nucleus (dLGN) we combined a Golgi deimpregnation technique (Fairén et al. 1977) with the Nissl staining. The two types of neurons show numerous characteristic features in Golgi preparations (Brauer and Schober 1973, Grossman et al. 1973, Brauer et al. 1974, Winkelmann et al. 1976, 1979). After application of the combined method it is obvious that neuronal somata exhibit also features which make it possible to identify these types of neurons in Nissl stained series. GCR-neurons are characterized by a very broad cytoplasmic portion, whereas a particularly thin cytoplasm rim is typical of I-neurons. Our findings confirm former results obtained by analysis of Nissl material (Werner and Kruger 1973, Werner et al. 1975, Werner and Winkelmann 1976, Werner et al. 1984). In these investigations, special attention was paid to cytoplasmic and nuclear characteristics in order to elucidate the ratio of GCR-/I-neurons (13:1) and the internal dLGN topography. It is still discussed if the described cytological features can be taken as basis for the classification of GCR- and I-neurons in other species.

  4. Sexual behavior in male rats after radiofrequency or dopamine-depleting lesions in nucleus accumbens.

    PubMed

    Liu, Y C; Sachs, B D; Salamone, J D

    1998-06-01

    Considerable neurochemical evidence links dopamine (DA) in nucleus accumbens (NAcc) to male sexual behavior. The present experiments were conducted to extend this information to the male's sexual response to remote stimuli from estrous female (noncontact erection; NCE). Male rats were tested for copulation and NCE after either 6-hydroxydopamine (6-OHDA) or radiofrequency (RF) lesions in NAcc). Males with an average 78% depletion of DA in NAcc had a lower incidence of NCE, longer latency to display NCE, and fewer erections. DA-depleted males also had less locomotor activity after injections of d-amphetamine, and reductions in apomorphine-induced yawning, but a normal incidence of penile erection. Males with RF lesions of the NAcc had longer NCE latencies. All males copulated to ejaculation after either 6-OHDA or RF lesions with little or no deficit, although the 6-OHDA-treated males had longer intromission latencies. The NCE deficit supports the hypothesized role of NAcc DA in arousal processes in responding to remote cues from estrous females. The minimal effect of lesions on copulation suggests that the presence of additional proximal stimulation during copulation may overcome the deficits induced by DA depletions or lesions in NAcc.

  5. GABA selectively controls the secretory activity of oxytocin neurons in the rat supraoptic nucleus.

    PubMed

    Engelmann, Mario; Bull, Philip M; Brown, Colin H; Landgraf, Rainer; Horn, Thomas F W; Singewald, Nicolas; Ludwig, Mike; Wotjak, Carsten T

    2004-02-01

    Recently we reported that a single social defeat experience triggers the release of oxytocin (OXT) from somata and dendrites, but not axon terminals, of neurons of the hypothalamic-neurohypophysial system. To further investigate the regulatory mechanisms underlying this dissociated release, we exposed male Wistar rats to a 30-min social defeat and monitored release of the inhibitory amino acids gamma amino butyric acid (GABA) and taurine within the hypothalamic supraoptic nucleus (SON) using microdialysis. Social defeat caused a significant increase in the release of both GABA and taurine within the SON (up to 480%; P < 0.01 vs. prestress release). To reveal the physiological significance of centrally released GABA, the specific GABAA-receptor antagonist bicuculline (0.02 mm) was administered into the SON via retrodialysis. This approach caused a significant increase in the release of OXT both within the SON and into the blood under basal conditions and during stress (up to 300 and 200%, respectively; P < 0.05 vs. basal values), without affecting plasma vasopressin. Electrophysiological studies confirmed the selective action of bicuculline on the firing activity of OXT neurons in the SON. Taken together, our data demonstrate that GABA is released within the SON during emotional stress to act as a selective inhibitor of both central and peripheral OXT secretion.

  6. Sensorimotor processing in the newborn rat red nucleus during active sleep.

    PubMed

    Del Rio-Bermudez, Carlos; Sokoloff, Greta; Blumberg, Mark S

    2015-05-27

    Sensory feedback from sleep-related myoclonic twitches is thought to drive activity-dependent development in spinal cord and brain. However, little is known about the neural pathways involved in the generation of twitches early in development. The red nucleus (RN), source of the rubrospinal tract, has been implicated in the production of phasic motor activity during active sleep in adults. Here we hypothesized that the RN is also a major source of motor output for twitching in early infancy, a period when twitching is an especially abundant motor behavior. We recorded extracellular neural activity in the RN during sleep and wakefulness in 1-week-old unanesthetized rats. Neurons in the RN fired phasically before twitching and wake movements of the contralateral forelimb. A subpopulation of neurons in the RN exhibited a significant peak of activity after forelimb movement onset, suggesting reafferent sensory processing. Consistent with this observation, manual stimulation of the forelimb evoked RN responses. Unilateral inactivation of the RN using a mixture comprising GABAA, GABAB, and glycine receptor agonists caused an immediate and temporary increase in motor activity followed by a marked and prolonged decrease in twitching and wake movements. Altogether, these data support a causal role for the RN in infant motor behavior. Furthermore, they indicate that twitching, which is characterized by discrete motor output and reafferent input, provides an opportunity for sensorimotor integration and activity-dependent development of topography within the newborn RN.

  7. Excitatory GABAergic synaptic potentials in the mesencephalic trigeminal nucleus of adult rat in vitro.

    PubMed

    Yokomizo, Y; Murai, Y; Tanaka, E; Inokuchi, H; Kusukawa, J; Higashi, H

    2005-04-01

    The mesencephalic trigeminal nucleus (MesV) contains the somata of primary afferent neurons innervating masticatory muscle spindles and the periodontal membrane. MesV afferent somata are unique in receiving synaptic inputs. Intracellular recordings in coronal pontine slices from adult rats were made from MesV neurons identified by having Cs-sensitive inward rectification and pseudounipolar morphology. Stimuli near the MesV evoked either a cluster of action potentials superimposed on a postsynaptic potential (PSP) or an antidromic spike at resting membrane potential (RMP). Membrane hyperpolarization revealed that each cluster of action potentials consisted of an antidromic spike and a subsequent PSP. Evoked PSPs in slices and miniature postsynaptic currents (mPSCs) recorded using whole-cell patch in dissociated MesV neurons were resistant to glutamate antagonists and strychnine but were reversibly abolished by 40 microM bicuculline. Superfusion of 1-10 mM GABA decreased input resistance and depolarized the membrane. Reversal potentials for evoked PSPs and GABA-induced depolarizations were similar and close to that for mPSCs which matched the Cl- equilibrium potential. Thus activation of synapses on MesV somata evokes GABAergic PSPs that generate action potentials at RMP in the adult. These data also indicate that primary afferent MesV neurons can act as interneurons in the central control of mastication.

  8. Dynamic properties of corticogeniculate excitatory transmission in the rat dorsal lateral geniculate nucleus in vitro

    PubMed Central

    Granseth, Björn

    2004-01-01

    The feedback excitation from the primary visual cortex to principal cells in the dorsal lateral geniculate nucleus (dLGN) is markedly enhanced with firing frequency. This property presumably reflects the ample short-term plasticity at the corticogeniculate synapse. The present study aims to explore corticogeniculate excitatory postsynaptic currents (EPSCs) evoked by brief trains of stimulation with whole-cell patch-clamp recordings in dLGN slices from DA-HAN rats. The EPSCs rapidly increased in amplitude with the first two or three impulses followed by a more gradual growth. A double exponential function with time constants 39 and 450 ms empirically described the growth for 5–25Hz trains. For lower train frequencies (down to 1Hz) a third component with time constant 4.8 s had to be included. The different time constants are suggested to represent fast and slow components of facilitation and augmentation. The time constant of the fast component changed with the extracellular calcium ion concentration as expected for a facilitation mechanism involving an endogenous calcium buffer that is more efficiently saturated with larger calcium influx. Concerning the function of the corticogeniculate feedback pathway, the different components of short-term plasticity interacted to increase EPSC amplitudes on a linear scale to firing frequency in the physiological range. This property makes the corticogeniculate synapse well suited to function as a neuronal amplifier that enhances the thalamic transfer of visual information to the cortex. PMID:14724201

  9. Participation of thalamic nuclei in the elaboration of conditioned avoidance reflexes of rats. VII. Lesions of the nucleus lateralis posterior.

    PubMed

    Klingberg, F; Klingberg, H

    1980-01-01

    Bilateral lesions of the nucleus laterials posterior thalami (LP) scarcely changed preoperatively learnt conditioned avoidance responses (CAR) in a runway and the Y-maze. Postoperative elaboration of CAR showed some difficulties in the runway which were increased during alternation training in the Y-maze. All rats with LP lesions had severe disturbances of spatial orientation in new situations, which could be overcome by training.

  10. Taste coding in the parabrachial nucleus of the pons in awake, freely licking rats and comparison with the nucleus of the solitary tract.

    PubMed

    Weiss, Michael S; Victor, Jonathan D; Di Lorenzo, Patricia M

    2014-04-01

    In the rodent, the parabrachial nucleus of the pons (PbN) receives information about taste directly from the nucleus of the solitary tract (NTS). Here we examined how information about taste quality (sweet, sour, salty, and bitter) is conveyed in the PbN of awake, freely licking rats, with a focus on how this information is transformed from the incoming NTS signals. Awake rats with electrodes in the PbN had free access to a lick spout that delivered taste stimuli (5 consecutive licks; 100 mM NaCl, 10 mM citric acid, 0.01 mM quinine HCl, or 100 mM sucrose and water) or water (as a rinse) on a variable-ratio schedule. To assess temporal coding, a family of metrics that quantifies the similarity of two spike trains in terms of spike count and spike timing was used. PbN neurons (n = 49) were generally broadly tuned across taste qualities with variable response latencies. Some PbN neurons were quiescent during lick bouts, and others, some taste responsive, showed time-locked firing to the lick pattern. Compared with NTS neurons, spike timing played a larger role in signaling taste in the first 2 s of the response, contributing significantly in 78% (38/49) of PbN cells compared with 45% of NTS cells. Also, information from temporal coding increased at a faster rate as the response unfolded over time in PbN compared with NTS. Collectively, these data suggest that taste-related information from NTS converges in the PbN to enable a subset of PbN cells to carry a larger information load.

  11. Acute repeated intracerebroventricular injections of angiotensin II reduce agonist and antagonist radioligand binding in the paraventricular nucleus of the hypothalamus and median preoptic nucleus in the rat brain.

    PubMed

    Speth, Robert C; Vento, Peter J; Carrera, Eduardo J; Gonzalez-Reily, Luz; Linares, Andrea; Santos, Kira; Swindle, Jamala D; Daniels, Derek

    2014-10-02

    Angiotensin II (Ang II) stimulates water and saline intakes when injected into the brain of rats. This arises from activation of the AT1 Ang II receptor subtype. Acute repeated injections, however, decrease the water intake response to Ang II without affecting saline intake. Previous studies provide evidence that Ang II-induced water intake is mediated via the classical G protein coupling pathway, whereas the saline intake caused by Ang II is mediated by an ERK 1/2 MAP kinase signaling pathway. Accordingly, the different behavioral response to repeated injections of Ang II may reflect a selective effect on G protein coupling. To test this hypothesis, we examined the binding of a radiolabeled agonist ((125)I-sarcosine(1) Ang II) and a radiolabeled antagonist ((125)I-sarcosine(1), isoleucine(8) Ang II) in brain homogenates and tissue sections prepared from rats given repeated injections of Ang II or vehicle. Although no treatment-related differences were found in hypothalamic homogenates, a focus on specific brain structures using receptor autoradiography, found that the desensitization treatment reduced binding of both radioligands in the paraventricular nucleus of the hypothalamus (PVN) and median preoptic nucleus (MnPO), but not in the subfornical organ (SFO). Because G protein coupling is reported to have a selective effect on agonist binding without affecting antagonist binding, these findings do not support a G protein uncoupling treatment effect. This suggests that receptor number is more critical to the water intake response than the saline intake response, or that pathways downstream from the G protein mediate desensitization of the water intake response.

  12. Taste coding in the parabrachial nucleus of the pons in awake, freely licking rats and comparison with the nucleus of the solitary tract

    PubMed Central

    Weiss, Michael S.; Victor, Jonathan D.

    2013-01-01

    In the rodent, the parabrachial nucleus of the pons (PbN) receives information about taste directly from the nucleus of the solitary tract (NTS). Here we examined how information about taste quality (sweet, sour, salty, and bitter) is conveyed in the PbN of awake, freely licking rats, with a focus on how this information is transformed from the incoming NTS signals. Awake rats with electrodes in the PbN had free access to a lick spout that delivered taste stimuli (5 consecutive licks; 100 mM NaCl, 10 mM citric acid, 0.01 mM quinine HCl, or 100 mM sucrose and water) or water (as a rinse) on a variable-ratio schedule. To assess temporal coding, a family of metrics that quantifies the similarity of two spike trains in terms of spike count and spike timing was used. PbN neurons (n = 49) were generally broadly tuned across taste qualities with variable response latencies. Some PbN neurons were quiescent during lick bouts, and others, some taste responsive, showed time-locked firing to the lick pattern. Compared with NTS neurons, spike timing played a larger role in signaling taste in the first 2 s of the response, contributing significantly in 78% (38/49) of PbN cells compared with 45% of NTS cells. Also, information from temporal coding increased at a faster rate as the response unfolded over time in PbN compared with NTS. Collectively, these data suggest that taste-related information from NTS converges in the PbN to enable a subset of PbN cells to carry a larger information load. PMID:24381029

  13. The neonatal neurotoxicity of monosodium L-glutamate on the sexually dimorphic nucleus of the preoptic area in rats.

    PubMed

    Hsieh, Y L; Hsu, C; Lue, S I; Hsu, H K; Peng, M T

    1997-01-01

    The neurotoxic effect of monosodium L-glutamate (MSG) on the morphologies in the darkly stained sexually dimorphic nucleus of the preoptic area (SDN-POA) and the lighter-staining surrounding area (non-SDN-POA) within the medial preoptic nucleus (MPN) was evaluated. Male and female Long-Evans rats were used. MSG (4 mg/g of body weight) was administered subcutaneously to pups on days 1 and 3 postnatally. Normal saline was used as the vehicle. At the age of 6 months, the rats were sacrificed and the brain tissues were fixed for histological examination. The morphological changes, i.e., total volume, density, total neuron number, neuronal nuclear volume (NNV) and ratio of pyknosis, of the SDN-POA and non-SDN-POA within the MPN, were estimated using the AMS VIDS III semiautomatic image-analytic system. The results indicate that neonatal MSG treatment caused significant neuronal loss and decreases in total volume of the SDN-POA and non-SDN-POA of male and female rats. However, only the SDN-POA of MSG-treated male rats showed a significant increase of pyknosis and decrease of neuronal density. A significant enlargement of NNV in the SDN-POA and non-SDN-POA was observed in the MSG-treated male rats. These results indicate that the MPN shows sex-specific and area-specific changes after neonatal neurotoxicity due to MSG.

  14. Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats.

    PubMed

    Hegarty, Deborah M; Hermes, Sam M; Largent-Milnes, Tally M; Aicher, Sue A

    2014-11-01

    We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats

    PubMed Central

    Hegarty, Deborah M.; Hermes, Sam M.; Largent-Milnes, Tally M.; Aicher, Sue A.

    2014-01-01

    We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings. PMID:24996127

  16. Effects of Food Restriction on Expression of Place Conditioning and Biochemical Correlates in Rat Nucleus Accumbens

    PubMed Central

    Jung, Caroline; Rabinowitsch, Ariana; Lee, Wei Ting; Zheng, Danielle; Cabeza de Vaca, Soledad; Carr, Kenneth D.

    2016-01-01

    Rationale When ad libitum fed rats undergo cocaine place preference conditioning (CPP) but are switched to food restriction for testing, CPP becomes resistant to extinction and correlates with phosphorylation of AMPA receptor GluA1 at Ser845 in nucleus accumbens (NAc) core. Objectives This study tested whether food restriction increases persistence of morphine CPP and conditioned place aversions (CPA) induced by LiCl and naloxone-precipitated morphine withdrawal. Materials and methods Ad libitum fed rats were conditioned with morphine (6.0 mg/kg, i.p.), LiCl (50.0/75.0 mg/kg, i.p.), or naloxone (1.0 mg/kg, s.c.) 22 hours post-morphine (20.0 mg/kg, s.c.). Half the subjects were then switched to food restriction. Daily testing resumed three weeks later and brains were harvested when one diet group met extinction criterion. Western analyses probed for pSer845-GluA1, pERK1 and pERK2 in NAc. Results Food restriction increased persistence of morphine CPP and preference scores correlated with pSer845-GluA1 in NAc core and shell. LiCl CPA was curtailed by food restriction, yet pSer845-GluA1 and pERK2 were elevated in NAc core of food restricted rats. Food restriction increased persistence of naloxone CPA, elevated pSer845-GluA1 in NAc core and shell, and aversion scores were negatively correlated with pERK1 and pERK2 in NAc core. Conclusions These results suggest that food restriction prolongs responsiveness to environmental contexts paired with subjective effects of both morphine and morphine withdrawal. A mechanistic scheme, attributing these effects to upregulation of pSer845-GluA1, but subject to override by CPA-specific, pERK2-mediated extinction learning, is explored to accommodate opposite effects of food restriction on LiCl and naloxone CPA. PMID:27376947

  17. Conditioned taste aversion and Ca/calmodulin-dependent kinase II in the parabrachial nucleus of rats.

    PubMed

    Krivanek, J

    2001-07-01

    Bielavska and colleagues (Bielavska, Sacchetti, Baldi, & Tassoni, 1999) have recently shown that KN-62, an inhibitor of calcium/calmodulin-dependent kinase II (CaCMK), induces conditioned taste aversion (CTA) when introduced into the parabrachial nucleus (PBN) of rats. The aim of the present report was to assess whether activity of CaCMK in the PBN is changed during CTA. We induced CTA in one group of rats by pairing saccharin consumption with an ip injection of lithium chloride. Another group of rats received lithium alone (without being paired with saccharin consumption) to test whether lithium has an effect on CaCMK in the PBN, independent of those effects due to training. In animals receiving CTA training, CaCMK activity in extracts of PBN was reduced by approximately 30% at the postacquisition intervals of 12, 24, and 48 h, compared to control animals receiving saccharin with saline injection. By 120 h after CTA training, no effect on CaCMK was present. At those postacquisition intervals showing CaCMK activity effects due to CTA, there were no effects attributable to lithium alone. Lithium alone produced only a short-lasting reduction in CaCMK activity (at 20 min a 30% decrease, at 60 min a 23% decrease; and at 6, 12, and 24 h no decrease). The time course of lithium-induced effects differed markedly from that of CTA training. All changes were Ca2+/- -dependent; we did not observe any changes in Ca-independent activity. CTA effects on CaCMK were selective for PBN, insofar as we did not observe any CTA effects on CaCMK in the visual cortex, a brain region unrelated to taste pathways. Since CTA produces a relatively long-lasting reduction in CaCMK activity (lasting 2 days or more) specifically in the PBN, which is critical a relay for taste information, the reduction of CaCMK activity may enable the consolidation of taste memory in an aversive situation.

  18. Autoradiographic localization of angiotensin II receptors in rat brain

    SciTech Connect

    Mendelsohn, F.A.O.; Quirion, R.; Saavedra, J.M.; Aguilera, G.; Catt, K.J.

    1984-03-01

    The /sup 125/I-labeled agonist analog (1-sarcosine)-angiotensin II ((Sar/sup 1/)AII) bound with high specificity and affinity (K/sub a/ = 2 x 10/sup 9/ M/sup -1/) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of AII receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of AII receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, pre- and parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that AII receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of AII receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of AII as a neuropeptide in the central nervous system. 75 references, 2 figures.

  19. Autoradiographic localization of angiotensin II receptors in rat brain.

    PubMed Central

    Mendelsohn, F A; Quirion, R; Saavedra, J M; Aguilera, G; Catt, K J

    1984-01-01

    The 125I-labeled agonist analog [1-sarcosine]-angiotensin II ( [Sar1]AII) bound with high specificity and affinity (Ka = 2 X 10(9) M-1) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of AII receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of AII receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, pre- and parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that AII receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of AII receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of AII as a neuropeptide in the central nervous system. Images PMID:6324205

  20. Neuronal and Endothelial Nitric Oxide Synthases in the Paraventricular Nucleus Modulate Sympathetic Overdrive in Insulin-Resistant Rats

    PubMed Central

    Lu, Qing-Bo; Feng, Xue-Mei; Tong, Ning; Sun, Hai-Jian; Ding, Lei; Wang, Yu-Jiao; Wang, Xuan; Zhou, Ye-Bo

    2015-01-01

    A central mechanism participates in sympathetic overdrive during insulin resistance (IR). Nitric oxide synthase (NOS) and nitric oxide (NO) modulate sympathetic nerve activity (SNA) in the paraventricular nucleus (PVN), which influences the autonomic regulation of cardiovascular responses. The aim of this study was to explore whether the NO system in the PVN is involved in the modulation of SNA in fructose-induced IR rats. Control rats received ordinary drinking water, whereas IR rats received 12.5% fructose-containing drinking water for 12 wks to induce IR. Basal SNA was assessed based on the changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to chemicals administered to the PVN. We found an increased plasma norepinephrine level but significantly reduced NO content and neuronal NOS (nNOS) and endothelial NOS (eNOS) protein expression levels in the PVN of IR rats compared to Control rats. No difference in inducible NOS (iNOS) protein expression was observed between the two groups. In anesthetized rats, the microinjection of sodium nitroprusside (SNP), an NO donor, or Nω-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of NOS, into the PVN significantly decreased and increased basal SNA, respectively, in both normal and IR rats, but these responses to SNP and L-NAME in IR rats were smaller than those in normal rats. The administration of selective inhibitors of nNOS or eNOS, but not iNOS, to the PVN significantly increased basal SNA in both groups, but these responses were also smaller in IR rats. Moreover, IR rats exhibited reduced nNOS and eNOS activity in the PVN. In conclusion, these data indicate that the decreased protein expression and activity levels of nNOS and eNOS in the PVN lead to a reduction in the NO content in the PVN, thereby contributing to a subsequent enhancement in sympathoexcitation during IR. PMID:26485682

  1. Hydrogen Sulfide in Paraventricular Nucleus Enhances Sympathetic Activity and Cardiac Sympathetic Afferent Reflex in Chronic Heart Failure Rats

    PubMed Central

    Gan, Xian-Bing; Liu, Tong-Yan; Xiong, Xiao-Qing; Chen, Wei-Wei; Zhou, Ye-Bo; Zhu, Guo-Qing

    2012-01-01

    Background Intracerebroventricular infusion of NaHS, a hydrogen sulfide (H2S) donor, increased mean arterial pressure (MAP). This study was designed to determine the roles of H2S in the paraventricular nucleus (PVN) in modulating sympathetic activity and cardiac sympathetic afferent reflex (CSAR) in chronic heart failure (CHF). Methodology/Principal Findings CHF was induced by left descending coronary artery ligation in rats. Renal sympathetic nerve activity (RSNA) and MAP were recorded under anesthesia. CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. PVN microinjection of low doses of a H2S donor, GYY4137 (0.01 and 0.1 nmol), had no significant effects on RSNA, MAP and CSAR. High doses of GYY4137 (1, 2 and 4 nmol) increased baseline RSNA, MAP and heart rate (HR), and enhanced CSAR. The effects were greater in CHF rats than sham-operated rats. A cystathionine-β-synthase (CBS) inhibitor, hydroxylamine (HA) in PVN had no significant effect on the RSNA, MAP and CSAR. CBS activity and H2S level in the PVN were decreased in CHF rats. No significant difference in CBS level in PVN was found between sham-operated rats and CHF rats. Stimulation of cardiac sympathetic afferents with capsaicin decreased CBS activity and H2S level in the PVN in both sham-operated rats and CHF rats. Conclusions Exogenous H2S in PVN increases RSNA, MAP and HR, and enhances CSAR. The effects are greater in CHF rats than those in sham-operated rats. Endogenous H2S in PVN is not responsible for the sympathetic activation and enhanced CSAR in CHF rats. PMID:23166827

  2. Dopamine-dependent hyperactivity in the rat following manipulation of GABA mechanisms in the region of the nucleus accumbens.

    PubMed

    Pycock, C J; Horton, R W

    1979-01-01

    The effect of manipulation of GABA mechanisms in the region of the nucleus accumbens on dopamine-dependent locomotor hyperactivity in the rat has been studied. Two models of hyperactivity were used: (1) the injection of dopamine into the region of the nucleus accumbens in nialamide-pretreated animals and (2) the systemic administration of d-amphetamine. Both GABA and the GABA agonist 3-aminopropane sulphonic acid (3-APS) depressed hyperactivity in a dose-related manner. High concentrations of GABA (greater than 100 micrograms) were required to produce a significant effect and the response was short-lived possibly reflecting the efficient GABA inactivating mechanisms. 3-APS proved to be approximately 10 times more potent as compared to GABA in the dopamine-accumbens hyperactivity model. Conversely GABA receptor antagonism with low doses of either picrotoxin or bicuculline enhanced the mild locomotor response induced by a low dose of dopamine injected into the nucleus accumbens. However such results were difficult to evaluate fairly as higher doses of the GABA antagonists resulted in varying degrees of generalized seizures. Blockade of GABA uptake systems with cis-1, 3-aminocyclohexane carboxylic acid (ACHC), nipecotic acid or beta-alanine within the region of the nucleus accumbens produced dose-related depression of dopamine-dependent hyperactivity in both models. GABA uptake blockade (nipecotic acid) significantly enhanced the GABA-mediated depression of hyperactivity induced by bilateral injection of dopamine into the nucleus accumbens. The results demonstrate an inhibitory action of GABA and drugs facilitating GABA-ergic transmission on dopamine-dependent hyperactivity in the rat. Although open to criticisms of not being able to distinguish between true GABA effects and the results of non-specific neuronal depression the hyperactivity model underlines the potency of the GABA uptake blocking compounds and their possible potential for future clinical use.

  3. Prediction of periventricular leukomalacia. Part II

    PubMed Central

    Samanta, Biswanath; Bird, Geoffrey L.; Kuijpers, Marijn; Zimmerman, Robert A.; Jarvik, Gail P.; Wernovsky, Gil; Clancy, Robert R.; Licht, Daniel J.; Gaynor, J. William; Nataraj, Chandrasekhar

    2009-01-01

    Summary Objective The objective of Part II is to analyze the dataset of extracted hemodynamic features (Case 3 of Part I) through computational intelligence (CI) techniques for identification of potential prognostic factors for periventricular leukomalacia (PVL) occurrence in neonates with congenital heart disease. Methods The extracted features (Case 3 dataset of Part I) were used as inputs to CI based classifiers, namely, multi-layer perceptron (MLP) and probabilistic neural network (PNN) in combination with genetic algorithms (GA) for selection of the most suitable features predicting the occurrence of PVL. The selected features were next used as inputs to a decision tree (DT) algorithm for generating easily interpretable rules of PVL prediction. Results Prediction performance for two CI based classifiers, MLP and PNN coupled with GA are presented for different number of selected features. The best prediction performances were achieved with 6 and 7 selected features. The prediction success was 100% in training and the best ranges of sensitivity (SN), specificity (SP) and accuracy (AC) in test were 60-73%, 74-84% and 71-74%, respectively. The identified features when used with the DTalgorithm gave best SN, SP and AC in the ranges of 87-90% in training and 80-87%, 74-79% and 79-82% in test. Among the variables selected in CI, systolic and diastolic blood pressures, and pCO2 figured prominently similar to Part I. Decision tree based rules for prediction of PVL occurrence were obtained using the CI selected features. Conclusions The proposed approach combines the generalization capability of CI based feature selection approach and generation of easily interpretable classification rules of the decision tree. The combination of CI techniques with DT gave substantially better test prediction performance than using CI and DT separately. PMID:19162456

  4. Chronic Methamphetamine Self-Administration Dysregulates Oxytocin Plasma Levels and Oxytocin Receptor Fibre Density in the Nucleus Accumbens Core and Subthalamic Nucleus of the Rat.

    PubMed

    Baracz, S J; Parker, L M; Suraev, A S; Everett, N A; Goodchild, A K; McGregor, I S; Cornish, J L

    2016-04-01

    The neuropeptide oxytocin attenuates reward and abuse for the psychostimulant methamphetamine (METH). Recent findings have implicated the nucleus accumbens (NAc) core and subthalamic nucleus (STh) in oxytocin modulation of acute METH reward and relapse to METH-seeking behaviour. Surprisingly, the oxytocin receptor (OTR) is only modestly involved in both regions in oxytocin attenuation of METH-primed reinstatement. Coupled with the limited investigation of the role of the OTR in psychostimulant-induced behaviours, we primarily investigated whether there are cellular changes to the OTR in the NAc core and STh, as well as changes to oxytocin plasma levels, after chronic METH i.v. self-administration (IVSA) and after extinction of drug-taking. An additional aim was to examine whether changes to central corticotrophin-releasing factor (CRF) and plasma corticosterone levels were also apparent because of the interaction of oxytocin with stress-regulatory mechanisms. Male Sprague-Dawley rats were trained to lever press for i.v. METH (0.1 mg/kg/infusion) under a fixed-ratio 1 schedule or received yoked saline infusions during 2-h sessions for 20 days. An additional cohort of rats underwent behavioural extinction for 15 days after METH IVSA. Subsequent to the last day of IVSA or extinction, blood plasma was collected for enzyme immunoassay, and immunofluorescence was conducted on NAc core and STh coronal sections. Rats that self-administered METH had higher oxytocin plasma levels, and decreased OTR-immunoreactive (-IR) fibres in the NAc core than yoked controls. In animals that self-administered METH and underwent extinction, oxytocin plasma levels remained elevated, OTR-IR fibre density increased in the STh, and a trend towards normalisation of OTR-IR fibre density was evident in the NAc core. CRF-IR fibre density in both brain regions and corticosterone plasma levels did not change across treatment groups. These findings demonstrate that oxytocin systems, both centrally

  5. Mechanisms of cardiovascular actions of urocortins in the hypothalamic arcuate nucleus of the rat

    PubMed Central

    Chitravanshi, Vineet C.; Kawabe, Kazumi

    2013-01-01

    The presence of urocortins (UCNs) and corticotropin-releasing factor (CRF) receptors has been reported in the hypothalamic arcuate nucleus (ARCN). We have previously reported that UCNs are involved in central cardiovascular regulation. Based on this information, we hypothesized that the ARCN may be one of the sites where UCNs exert their central cardiovascular actions. Experiments were done in artificially ventilated, adult male Wistar rats anesthetized with urethane. Unilateral microinjections (30 nl) of UCN1 (0.12–2 mM) elicited decreases in mean arterial pressure (MAP) and heart rate (HR). Maximum cardiovascular responses were elicited by a 1 mM concentration of UCN1. Microinjections of UCN2 and UCN3 (1 mM each) into the ARCN elicited similar decreases in MAP and HR. UCN1 was used as a prototype for the other experiments described below. HR responses elicited by UCN1 were significantly attenuated by bilateral vagotomy. Prior microinjections of NBI-27914 (CRF-1 receptor antagonist) and astressin (CRF-1 receptor and CRF-2 receptor antagonist) (1 mM each) into the ARCN significantly attenuated the cardiovascular responses elicited by UCN1 microinjections at the same site. Microinjections of UCN1 into the ARCN decreased efferent renal sympathetic nerve activity. It was concluded that microinjections of UCN1, UCN2, and UCN3 into the ARCN elicited decreases in MAP and HR. Decreases in MAP, HR, and renal sympathetic nerve activity elicited by UCN1 microinjections into the ARCN were mediated via CRF receptors. Bradycardic responses to UCN1 were mediated via the activation of vagus nerves, and decreases in MAP may be mediated via decreases in sympathetic nerve activity. PMID:23686711

  6. Mechanisms of cardiovascular actions of urocortins in the hypothalamic arcuate nucleus of the rat.

    PubMed

    Chitravanshi, Vineet C; Kawabe, Kazumi; Sapru, Hreday N

    2013-07-15

    The presence of urocortins (UCNs) and corticotropin-releasing factor (CRF) receptors has been reported in the hypothalamic arcuate nucleus (ARCN). We have previously reported that UCNs are involved in central cardiovascular regulation. Based on this information, we hypothesized that the ARCN may be one of the sites where UCNs exert their central cardiovascular actions. Experiments were done in artificially ventilated, adult male Wistar rats anesthetized with urethane. Unilateral microinjections (30 nl) of UCN1 (0.12-2 mM) elicited decreases in mean arterial pressure (MAP) and heart rate (HR). Maximum cardiovascular responses were elicited by a 1 mM concentration of UCN1. Microinjections of UCN2 and UCN3 (1 mM each) into the ARCN elicited similar decreases in MAP and HR. UCN1 was used as a prototype for the other experiments described below. HR responses elicited by UCN1 were significantly attenuated by bilateral vagotomy. Prior microinjections of NBI-27914 (CRF-1 receptor antagonist) and astressin (CRF-1 receptor and CRF-2 receptor antagonist) (1 mM each) into the ARCN significantly attenuated the cardiovascular responses elicited by UCN1 microinjections at the same site. Microinjections of UCN1 into the ARCN decreased efferent renal sympathetic nerve activity. It was concluded that microinjections of UCN1, UCN2, and UCN3 into the ARCN elicited decreases in MAP and HR. Decreases in MAP, HR, and renal sympathetic nerve activity elicited by UCN1 microinjections into the ARCN were mediated via CRF receptors. Bradycardic responses to UCN1 were mediated via the activation of vagus nerves, and decreases in MAP may be mediated via decreases in sympathetic nerve activity.

  7. Striatal Molecular Signature of Subchronic Subthalamic Nucleus High Frequency Stimulation in Parkinsonian Rat

    PubMed Central

    Lortet, Sylviane; Lacombe, Emilie; Boulanger, Nicolas; Rihet, Pascal; Nguyen, Catherine; Goff, Lydia Kerkerian-Le; Salin, Pascal

    2013-01-01

    This study addresses the molecular mechanisms underlying the action of subthalamic nucleus high frequency stimulation (STN-HFS) in the treatment of Parkinson's disease and its interaction with levodopa (L-DOPA), focusing on the striatum. Striatal gene expression profile was assessed in rats with nigral dopamine neuron lesion, either treated or not, using agilent microarrays and qPCR verification. The treatments consisted in anti-akinetic STN-HFS (5 days), chronic L-DOPA treatment inducing dyskinesia (LIDs) or the combination of the two treatments that exacerbated LIDs. STN-HFS modulated 71 striatal genes. The main biological processes associated with the differentially expressed gene products include regulation of growth, of apoptosis and of synaptic transmission, and extracellular region is a major cellular component implicated. In particular, several of these genes have been shown to support survival or differentiation of striatal or of dopaminergic neurons. These results indicate that STN HFS may induce widespread anatomo-functional rearrangements in the striatum and create a molecular environment favorable for neuroprotection and neuroplasticity. STN-HFS and L-DOPA treatment share very few common gene regulation features indicating that the molecular substrates underlying their striatal action are mostly different; among the common effects is the down-regulation of Adrb1, which encodes the adrenergic beta-1- receptor, supporting a major role of this receptor in Parkinson's disease. In addition to genes already reported to be associated with LIDs (preprodynorphin, thyrotropin-releasing hormone, metabotropic glutamate receptor 4, cannabinoid receptor 1), the comparison between DOPA and DOPA/HFS identifies immunity-related genes as potential players in L-DOPA side effects. PMID:23593219

  8. Increased glutamate synaptic transmission in the nucleus raphe magnus neurons from morphine-tolerant rats

    PubMed Central

    Bie, Bihua; Pan, Zhizhong Z

    2005-01-01

    Currently, opioid-based drugs are the most effective pain relievers that are widely used in the treatment of pain. However, the analgesic efficacy of opioids is significantly limited by the development of tolerance after repeated opioid administration. Glutamate receptors have been reported to critically participate in the development and maintenance of opioid tolerance, but the underlying mechanisms remain unclear. Using whole-cell voltage-clamp recordings in brainstem slices, the present study investigated chronic morphine-induced adaptations in glutamatergic synaptic transmission in neurons of the nucleus raphe magnus (NRM), a key supraspinal relay for pain modulation and opioid analgesia. Chronic morphine significantly increased glutamate synaptic transmission exclusively in one class of NRM cells that contains μ-opioid receptors in a morphine-tolerant state. The adenylyl cyclase activator forskolin and the cAMP analog 8-bromo-cAMP mimicked the chronic morphine effect in control neurons and their potency in enhancing the glutamate synaptic current was significantly increased in neurons from morphine-tolerant rats. MDL12330a, an adenylyl cyclase inhibitor, and H89, a protein kinase A (PKA) inhibitor, reversed the increase in glutamate synaptic transmission induced by chronic morphine. In addition, PMA, a phorbol ester activator of protein kinase C (PKC), also showed an increased potency in enhancing the glutamate synaptic current in these morphine-tolerant cells. The PKC inhibitor GF109203X attenuated the chronic morphine effect. Taken together, these results suggest that chronic morphine increases presynaptic glutamate release in μ receptor-containing NRM neurons in a morphine-tolerant state, and that the increased glutamate synaptic transmission appears to involve an upregulation of both the cAMP/PKA pathway and the PKC pathway. This glutamate-mediated activation of these NRM neurons that are thought to facilitate spinal pain transmission may contribute to

  9. Estrogen replacement modulates voltage-gated potassium channels in rat presympathetic paraventricular nucleus neurons

    PubMed Central

    2013-01-01

    Background The hypothalamic paraventricular nucleus (PVN) is an important site in the regulation of the autonomic nervous system. Specifically, PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) play a regulatory role in the determination of the sympathetic outflow in the cardiovascular system. In the PVN-RVLM neurons, the estrogen receptor β is expressed. However, to date, the effects of estrogen on PVN-RVLM neurons have not been reported. The present study investigated estrogen-mediated modulation of two voltage-gated potassium channel (Kv) subunits, Kv4.2 and Kv4.3, that are expressed predominantly in PVN neurons and the functional current of Kv4.2 and Kv4.3, the transient outward potassium current (IA). Results Single-cell real-time RT-PCR analysis showed that 17β-estradiol (E2) replacement (once daily for 4 days) selectively down-regulated Kv4.2 mRNA levels in the PVN-RVLM neurons of ovariectomized female rats. There was no change in Kv4.3 levels. Whole-cell patch-clamp recordings demonstrated that E2 also diminished IA densities. Interestingly, these effects were most apparent in the dorsal cap parvocellular subdivision of the PVN. E2 also shortened a delay in the excitation of the PVN-RVLM neurons. Conclusions These findings demonstrate that E2 exerts an inhibitory effect on the functions of IA, potentially by selectively down-regulating Kv4.2 but not Kv4.3 in PVN-RVLM neurons distributed in a specific parvocellular subdivision. PMID:24180323

  10. Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro

    NASA Technical Reports Server (NTRS)

    Phelan, K. D.; Gallagher, J. P.

    1992-01-01

    We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.

  11. Discharge patterns of principal cells and interneurones in lateral geniculate nucleus of rat

    PubMed Central

    Burke, W.; Sefton, Ann Jervie

    1966-01-01

    1. The cells of the lateral geniculate nucleus of the rat are classified into one of two distinct groups on the basis of their responses to a single shock to optic nerve or visual cortex. The distinctive difference between these two groups is that the P cells (87% of all cells) responded with short bursts of 1-5 spikes, whereas the I cells (13%) responded with long bursts of about 10 spikes. Both groups give recurring bursts at intervals of 100 msec or more for a total duration of up to about 5 sec. 2. The majority of P cells (75%) have a lower threshold for late firing than for early firing. The majority of I cells (62%) have about the same threshold and all I cells have very low thresholds. 3. To stimulation of the optic nerve the mean latency of the first spikes of all P cells is 4·4 msec. The mean latency of the first spikes of all I cells is 5·8 msec. The latency of the earliest spike in an I cell is 0·9 msec longer than the earliest spike in a P cell. 4. To stimulation of the visual cortex the latency of the earliest spike in an I cell is 1·0 msec longer than the earliest spike in a P cell. Most P cells (78%) respond with either very short latency (less than 1·7 msec) or with a wave form characteristic of antidromic invasion or both. No I cell has either of these characterstics. 5. It is concluded that P cells are principal cells projecting to visual cortex and that I cells are interneurones. PMID:5972163

  12. Protective effect of histamine microinjected into cerebellar fastigial nucleus on stress gastric mucosal damage in rats.

    PubMed

    Qiao, Xiao; Yang, Jun; Fei, Su-Juan; Zhu, Jin-Zhou; Zhu, Sheng-Ping; Liu, Zhang-Bo; Li, Ting-Ting; Zhang, Jian-Fu

    2015-12-10

    In the study, we investigated the effect of histamine microinjected into cerebellar fastigial nucleus (FN) on stress gastric mucosal damage (SGMD), and its mechanisms in rats. The model of SGMD was established by restraining and water (21±1°C)-immersion for 3h. The gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal damage. Histamine or receptor antagonist was microinjected into the FN. The decussation of superior cerebellar peduncle (DSCP) and the lateral hypothalamic area (LHA) were destroyed, respectively. The pathological changes of gastric mucosa were evaluated using biological signal acquisition system, Laser-Doppler flowmeter, and western blotting. We found that the microinjection of histamine (0.05, 0.5, and 5μg) into FN significantly attenuated the SGMD, in a dose-dependent manner, whereas, the microinjection of histamine H2 receptor antagonist, ranitidine, and glutamic acid decarboxylase antagonist, 3-mercaptopropionic acid (3-MPA) exacerbated the SGMD. The protective effect of histamine on SGMD was abolished by electrical lesion of DSCP or chemical ablation of LHA. The microinjection of histamine decreased the discharge frequency of the greater splanchnic nerve, and the gastric mucosal blood flow was increased. In addition, the cellular proliferation was enhanced, but the cellular apoptosis was reduced in the gastric mucosa. Also the pro-apoptosis protein, Bax, and caspase-3 were down-regulated, and the anti-apoptosis protein, Bcl-2 was up-regulated following microinjection of histamine. In conclusion, the FN participated in the regulation of SGMD after histamine microinjected into FN, and cerebellar-hypothalamic circuits (include: DSCP, LHA) contribute to the process, which may provide a new therapeutic strategy for SGMD.

  13. Depletion of glucose causes presynaptic inhibition of neuronal transmission in the rat dorsolateral septal nucleus.

    PubMed

    Akasu, T; Tsurusaki, M; Shoji, S

    1996-10-01

    The role of glucose in synaptic transmission was examined in the rat dorsolateral septal nucleus (DLSN) with single-microelectrode voltage-clamp and slice-patch technique. Removal of glucose from the oxygenated Krebs solution caused an outward current associated with an increased membrane conductance. The current-voltage relationship (I-V curve) showed that the hypoglycemia-induced outward current was reversed in polarity at the equilibrium potential for K+. Exposure of DLSN neurons to the glucose-free solution for 5-20 min depressed the excitatory postsynaptic current (EPSC), the inhibitory postsynaptic current (IPSC), and the late hyperpolarizing current (LHC). Replacement of glucose with 2-deoxy-D-glucose (2DG), an antimetabolic substrate, mimicked the deprivation of glucose. Mannoheptulose (10 mM) and dinitrophenol, inhibitors of glucose metabolism, also depressed the PSCs, even in the presence of 10 mM glucose. Glucose-free perfusion did not significantly depress the glutamate-induced inward current, indicating that the inhibition of the EPSC by the glucose-free perfusion was presynaptic. gamma-Aminobutyric acid (GABA)-induced outward currents were depressed by the glucose-free solution. Intracellular dialysis of DLSN neurons with a patch-pipette solution containing 5 mM ATP attenuated the hypoglycemia-induced outward current. Glucose-free superfusion consistently inhibited the IPSC and the LHC without changing the GABA-induced outward current in ATP-treated DLSN neurons. It is suggested that glucose metabolism directly regulates the release of both excitatory amino acids and GABA from the presynaptic nerve terminals.

  14. Astrocytes in the Rat Nucleus Tractus Solitarii Are Critical for Cardiovascular Reflex Control

    PubMed Central

    Lin, Li-Hsien; Moore, Steven A.; Jones, Susan Y.; McGlashon, Jacob

    2013-01-01

    We have shown that an antibody to dopamine-β-hydroxylase conjugated with saporin (anti-DBH-SAP) damages catecholamine neurons in the nucleus tractus solitarii (NTS) of rat, attenuates arterial baroreflexes, and leads to lability of arterial blood pressure, damage to cardiac myocytes, and, in some animals, sudden death. However, others have shown that injection of 6-hydroxydopamine (6-OHDA), a toxin devoid of saporin, also damaged NTS catecholamine neurons but did not lead to these cardiovascular changes. We found similar cardiovascular changes after injecting a different SAP conjugate to target NTS neurons with neurokinin (NK1) receptors. Because ribosome-inactivating proteins may be toxic to glia, we hypothesized that SAP, a ribosome-inactivating protein, might target glia whose loss could account for physiological changes. We tested this hypothesis by assessing effects on select neurons and on glia in the NTS after exposure to SAP, targeted SAP conjugates, or 6-OHDA. SAP and all SAP conjugates led to loss of immunoreactivity for glial fibrillary acidic protein, a marker for astrocytes, in the NTS while 6-OHDA did not. As reported previously, anti-DBH-SAP selectively killed noradrenergic neurons in the NTS while SAP conjugated to stabilized substance P (SSP-SAP) selectively killed neurons with NK1 receptors. In contrast, SAP produced no demonstrable neuronal damage. All injections led to activation of microglia in the NTS; however, only SAP and its conjugates attenuated cardiovascular reflexes while also producing lability of arterial pressure, damage to cardiac myocytes, and in some animals, sudden death. Thus, NTS astrocytes may play a role in mediating cardiovascular reflex transmission through the NTS. PMID:24259582

  15. Subthreshold oscillation of the membrane potential in magnocellular neurones of the rat supraoptic nucleus

    PubMed Central

    Boehmer, Gerd; Greffrath, Wolfgang; Martin, Erich; Hermann, Sven

    2000-01-01

    Electrophysiological properties and ionic basis of subthreshold oscillation of the membrane potential were examined in 104 magnocellular neurones of the rat supraoptic nucleus using intracellular recording techniques in a brain slice preparation. Subthreshold oscillation of the membrane potential occurring in all neurones examined was voltage dependent. Oscillation was initiated 7-12 mV negative to the threshold of fast action potentials. Oscillation was the result of neither excitatory nor inhibitory synaptic activity nor of electric coupling. Frequency analyses revealed a broad band frequency distribution of subthreshold oscillation waves (range 10-70 Hz). The frequency band of 15-33 Hz was observed in neurones depolarized close to the threshold of discharge. Subthreshold oscillation was blocked by TTX (1.25-2.5 μM) as well as by TEA (15 mM). Subthreshold oscillation was not blocked by low Ca2+-high Mg2+ superfusate, CdCl2, TEA (1-4.5 mM), 4-aminopyridine, apamin, charybdotoxin, iberiotoxin, BaCl2, carbachol and CsCl. During application of TTX, stronger depolarization induced high-threshold oscillation of the membrane potential at a threshold of about -32 mV. These oscillation waves occurred at a mean frequency of about 35 Hz and were blocked by CdCl2. Effects of ion channel antagonists suggest that subthreshold oscillation is generated by the interaction of a subthreshold sodium current and a subthreshold potassium current. The generation of high-threshold oscillation during TTX involves a high-threshold calcium current. Subthreshold oscillation of the membrane potential may be important for the inter-neuronal synchronization of discharge and for the amplification of synaptic events. PMID:10878105

  16. Components of after-hyperpolarization in magnocellular neurones of the rat supraoptic nucleus in vitro

    PubMed Central

    Greffrath, Wolfgang; Martin, Erich; Reuss, Stefan; Boehmer, Gerd

    1998-01-01

    The pharmacological sensitivity of hyperpolarizing components of spike train after-potentials was examined in sixty-one magnocellular neurones of the rat supraoptic nucleus using intracellular recording techniques in a brain slice preparation.In 26 % of all neurones a slow after-hyperpolarization (AHP) was observed in addition to a fast AHP. In 31 % of all neurones a depolarizing after-potential (DAP) was observed.The fast AHP was blocked by apamin whereas the slow AHP was blocked by charybdotoxin (ChTX). The DAP was enhanced by ChTX or a DAP was unmasked if not present during the control period.Low concentrations of TEA (0.15–1.5 mm) induced effects on the slow AHP and the DAP essentially resembling those of ChTX. The same was true for the effects of CoCl2 (1 mm).Spike train after-potentials were not affected by either iberiotoxin (IbTX), a selective high-conductance potassium (BK) channel antagonist, or margatoxin (MgTX), a Kv1.3 α-subunit antagonist.Kv1.3 α-subunit immunohistochemistry revealed that these units are not expressed in the somato-dendritic region of supraoptic neurones.The effects of ChTX, IbTX, MgTX, TEA, CoCl2 and CdCl2 on spike train after-potentials are interpreted in terms of an induction of the slow AHP by the activation of calcium-dependent potassium channels of intermediate single channel conductance (IK channels).The results suggest that at least the majority of supraoptic magnocellular neurones share the capability of generating both a slow AHP and a DAP. The slow AHP may act to control the expression of the DAP, thus regulating the excitability of magnocellular neurones. The interaction of the slow AHP and the DAP may be important for the control of phasic discharge. PMID:9806998

  17. Subthalamic nucleus activity in the awake hemiparkinsonian rat: relationships with motor and cognitive networks.

    PubMed

    Delaville, Claire; McCoy, Alex J; Gerber, Colin M; Cruz, Ana V; Walters, Judith R

    2015-04-29

    Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronized STN local field potential (LFP) activity with activity in motor cortex (MCx) and medial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively. Data show increases in STN and MCx 29-36 Hz LFP spectral power and coherence after dopamine depletion, which are reduced by apomorphine and levodopa treatments. In contrast, recordings from mPFC 3 weeks after dopamine depletion failed to show peaks in 29-36 Hz LFP power. However, mPFC and STN both showed peaks in the 45-55 Hz frequency range in LFP power and coherence during walking before and 21 days after dopamine depletion. Interestingly, power in this low gamma range was transiently reduced in both mPFC and STN after dopamine depletion but recovered by day 21. In contrast to the 45-55 Hz activity, the amplitude of the exaggerated 29-36 Hz rhythm in the STN was modulated by paw movement. Furthermore, as in PD patients, after dopamine treatment a third band (high gamma) emerged in the lesioned hemisphere. The results suggest that STN integrates activity from both motor and cognitive networks in a manner that varies with frequency, behavioral state, and the integrity of the dopamine system.

  18. Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens.

    PubMed

    Goda, Sailaja A; Piasecka, Joanna; Olszewski, Maciej; Kasicki, Stefan; Hunt, Mark J

    2013-07-01

    The nucleus accumbens (NAc) is a site critical for the actions of many drugs of abuse. Psychoactive compounds, such as N-methyl-D-aspartate receptor (NMDAR) antagonists, modify gamma (40-90) and high frequency oscillations (HFO, 130-180 Hz) in local field potentials (LFPs) recorded in the NAc. Lysergic acid diethylamide (LSD) and 2,5-dimethoxy-4-iodoamphetamine (DOI) are serotonergic hallucinogens and activation of 5HT2A receptors likely underlies their hallucinogenic effects. Whether these compounds can also modulate LFP oscillations in the NAc is unclear. This study aims to examine the effect of serotonergic hallucinogens on gamma and HFO recorded in the NAc and to test whether 5HT2A receptors mediate the effects observed. LFPs were recorded from the NAc of freely moving rats. Drugs were administered intraperitoneally. LSD (0.03-0.3 mg/kg) and DOI (0.5-2.0 mg/kg) increased the power and reduced the frequency of HFO. In contrast, the hallucinogens produced a robust reduction in the power of low (40-60 Hz), but not high gamma oscillations (70-90 Hz). MDL 11939 (1.0 mg/kg), a 5HT2A receptor antagonist, fully reversed the changes induced by DOI on HFO but only partially for the low gamma band. Equivalent increases in HFO power were observed after TCB-2 (5HT2A receptor agonist, 0.1-1.5 mg/kg), but not CP 809101 (5H2C receptor agonist, 0.1-3 mg/kg). Notably, hallucinogen-induced increases in HFO power were smaller than those produced by ketamine (25 mg/kg). Serotonergic hallucinogen-induced changes in HFO and gamma are mediated, at least in part, by stimulation of 5HT2A receptors. Comparison of the oscillatory changes produced by serotonergic hallucinogens and NMDAR antagonists are also discussed.

  19. Buprenorphine modulates methamphetamine-induced dopamine dynamics in the rat caudate nucleus.

    PubMed

    Pereira, Frederico C; Gough, Bobby; Macedo, Tice R; Ribeiro, Carlos F; Ali, Syed F; Binienda, Zbigniew K

    2011-01-01

    Methamphetamine (METH) abuse and addiction present a major problem in the United States and globally. Oxidative stress associated with exposure to METH mediates to the large extent METH-evoked neurotoxicity. While there are currently no medications approved for treating METH addiction, its pharmacology provides opportunities for potential pharmacotherapeutic adjuncts to behavioral therapy in the treatment of METH addiction. Opioid receptor agonists can modulate the activity of dopamine neurons and could, therefore, modify the pharmacodynamic effects of METH in the dopaminergic system. Efficacy of the adjunctive medication with buprenorphine has been demonstrated in the treatment of cocaine addiction extending beyond opiate addiction. We investigated the interactions of morphine (10 mg/kg) and buprenorphine (0.01 and 10 mg/kg) with METH (2 mg/kg) affecting striatal dopaminergic transmission. The extracellular concentration of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were determined using brain microdialysis coupled with high performance liquid chromatography with electrochemical detection (HPLC-ED) in the caudate nucleus of adult, awake, male Sprague-Dawley rats. Compared to METH alone, extracellular DA release was prolonged for 140 min without changes in DA peak-effect by combined treatment with morphine/METH. Morphine did not change DOPAC efflux evoked by METH. On the other hand, both buprenorphine doses attenuated the METH-induced DA peak-effect. However, whereas high buprenorphine dose extended DA outflow for 190 min, the low-dose abbreviated DA release. High buprenorphine dose also shortened METH-induced decrease in DOPAC efflux. Data confirm that opiates modulate dopaminergic neurotransmission evoked by METH. Alteration of dopaminergic response to METH challenge under buprenorphine may suggest effectiveness of buprenorphine treatment in METH addiction.

  20. The Good and Bad Differentially Encoded within the Subthalamic Nucleus in Rats

    PubMed Central

    Breysse, Emmanuel; Pelloux, Yann

    2015-01-01

    Abstract The subthalamic nucleus (STN) has only recently been added into the reward circuit. It has been shown to encode information regarding rewards (4% sucrose, 32% cocaine). To investigate the encoding of negative value, STN neurons were recorded in rats performing a task using discriminative stimuli predicting various rewards and especially during the replacement of a positive reinforcer (4% sucrose) by an aversive reinforcer (quinine). The results show that STN neurons encode information relative to both positive and aversive reinforcers via specialized subpopulations. The specialization is reset when the context is modified (change from a favorable context (4% vs 32% sucrose) to an unfavorable context (quinine vs 32% sucrose). An excitatory response to the cue light predicting the reward seems to be associated with the preferred situation, suggesting that STN plays a role in encoding the relative value of rewards. STN also seems to play a critical role in the encoding of execution error. Indeed, various subpopulations of neurons responding exclusively at early (i.e., “oops neurons”) or at correct lever release were identified. The oops neurons respond mostly when the preferred reward (32% sucrose) is missed. Furthermore, STN neurons respond to reward omission, suggesting a role in reward prediction error. These properties of STN neurons strengthen its position in the reward circuit as a key cerebral structure through which reward-related processes are mediated. It is particularly important given the fact that STN is the target of surgical treatment for Parkinson’s disease and obsessive compulsive disorders, and has been suggested for the treatment of addiction as well. PMID:26478913

  1. Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine.

    PubMed

    Ericson, Mia; Molander, Anna; Stomberg, Rosita; Söderpalm, Bo

    2006-06-01

    The mesolimbic dopamine (DA) system, projecting from the ventral tegmental area (VTA) to the nucleus accumbens (nAcc), is involved in reward-related behaviours and addictive processes, such as alcoholism and drug addiction. It was recently suggested that strychnine-sensitive glycine receptors (GlyR) in the nAcc regulate both basal and ethanol-induced mesolimbic DA activity via a neuronal loop involving endogenous activation of nicotinic acetylcholine receptors (nAChR) in the VTA. However, as the nAcc appears to contain few glycine-immunoreactive cell bodies or fibres, the question as to what may be the endogenous ligand for GlyRs in this brain region remains open. Here we have investigated whether the amino acid taurine could serve this purpose using in vivo microdialysis in awake, freely moving male Wistar rats. Local perfusion of taurine (1, 10 or 100 mm in the perfusate) increased DA levels in the nAcc. The taurine (10 mm)-induced DA increase was, similarly to that previously observed after ethanol, completely blocked by (i) perfusion of the competitive GlyR antagonist strychnine in the nAcc, (ii) perfusion of the nAChR antagonist mecamylamine (100 microm) in the VTA, and (iii) systemic administration of the acetylcholine-depleting drug vesamicol (0.4 mg/kg, i.p). The present results suggest that taurine may be an endogenous ligand for GlyRs in the nAcc and that the taurine-induced elevation of DA levels in this area, similarly to that observed after local ethanol, is mediated via a neuronal loop involving endogenous activation of nAChRs in the VTA.

  2. Sudden Death Following Selective Neuronal Lesions in the Rat Nucleus Tractus Solitarii

    PubMed Central

    Talman, William T.; Lin, Li-Hsien

    2013-01-01

    In efforts to assess baroreflex and cardiovascular responses in rats in which substance P (SP) or catecholamine transmission had been eliminated we studied animals after bilateral injections into the nucleus tractus solitarii (NTS) of SP or stabilized SP (SSP) conjugated to saporin (SP-SAP or SSP-SAP respectively) or SAP conjugated to an antibody to dopamine-β-hydroxylase (anti-DBH-SAP). We found that SP- and SSP-SAP eliminated NTS neurons that expressed the SP neurokinin-1 receptor (NK1R) while anti-DBH-SAP eliminated NTS neurons expressing tyrosine hydroxylase (TH) and DBH. The toxins were selective. Thus SP-or SSP-SAP did not eliminate TH/DBH neurons and anti-DBH-SAP did not eliminate NK1R neurons in the NTS. Each toxin, however, led to chronic lability of arterial blood pressure, diminished baroreflex function, cardiac ventricular irritability, coagulation necrosis of cardiac myocytes and, in some animals, sudden death associated with asystole. However, when TH/DBH neurons were targeted and eliminated by injection of 6-hydroxydopamine (6-OHDA), none of the cardiovascular or cardiac changes occurred. The studies reviewed here reveal that selective lesions of the NTS lead to altered baroreflex control and to cardiac changes that may lead to sudden death. Though the findings could support a role for SP or catecholamines in baroreflex transmission neither is proven in that NK1R colocalizes with glutamate receptors. Thus neurons with both are lost when treated with SP- or SSP-SAP. In addition, loss of catecholamine neurons after treatment with 6-OHDA does not affect cardiovascular control. Thus, the effect of the toxins may depend on an action of SAP independent of the effects of the SAP conjugates on targeted neuronal types. PMID:23245583

  3. Functional role of cyclic nucleotide-gated channels in rat medial vestibular nucleus neurons

    PubMed Central

    Podda, Maria Vittoria; D'Ascenzo, Marcello; Leone, Lucia; Piacentini, Roberto; Azzena, Gian Battista; Grassi, Claudio

    2008-01-01

    Although cyclic nucleotide-gated (CNG) channels are expressed in numerous brain areas, little information is available on their functions in CNS neurons. The aim of the present study was to define the distribution of CNG channels in the rat medial vestibular nucleus (MVN) and their possible involvement in regulating MVN neuron (MVNn) excitability. The majority of MVNn expressed both CNG1 and CNG2 A subunits. In whole-cell current-clamp experiments carried out on brainstem slices containing the MVNn, the membrane-permeant analogues of cyclic nucleotides, 8-Br-cGMP and 8-Br-cAMP (1 mm), induced membrane depolarizations (8.9 ± 0.8 and 9.2 ± 1.0 mV, respectively) that were protein kinase independent. The cGMP-induced depolarization was associated with a significant decrease in the membrane input resistance. The effects of cGMP on membrane potential were almost completely abolished by the CNG channel blockers, Cd2+ and l-cis-diltiazem, but they were unaffected by blockade of hyperpolarization-activated cyclic nucleotide-gated channels. In voltage-clamp experiments, 8-Br-cGMP induced non-inactivating inward currents (−22.2 ± 3.9 pA) with an estimated reversal potential near 0 mV, which were markedly inhibited by reduction of extracellular Na+ and Ca2+ concentrations. Membrane depolarization induced by CNG channel activation increased the firing rate of MVNn without changing the action potential shape. Collectively, these findings provide novel evidence that CNG channels affect membrane potential and excitability of MVNn. Such action should have a significant impact on the function of these neurons in sensory–motor integration processes. More generally, it might represent a broad mechanism for regulating the excitability of different CNS neurons. PMID:18048449

  4. Contribution of excitatory amino acid receptors of the retrotrapezoid nucleus to the sympathetic chemoreflex in rats.

    PubMed

    Takakura, Ana C; Moreira, Thiago S

    2011-10-01

    In the present study, we evaluated the role of glutamatergic mechanisms in the retrotrapezoid nucleus (RTN) in changes of splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) elicited by central and peripheral chemoreceptor activation. Mean arterial pressure (MAP), sSND and PND were recorded in urethane-anaesthetized, vagotomized, sino-aortic denervated and artificially ventilated male Wistar rats. Hypercapnia (10% CO(2)) increased MAP by 32 ± 4 mmHg, sSND by 104 ± 4% and PND amplitude by 101 ± 5%. Responses to hypercapnia were reduced after bilateral injection of the NMDA receptor antagonist d,l-2-amino-5-phosphonovalerate (AP-5; 100 mm in 50 nl) in the RTN (MAP increased by 16 ± 3 mmHg, sSND by 82 ± 3% and PND amplitude by 63 ± 7%). Bilateral injection of the non-NMDA receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 100 mm in 50 nl) and the metabotropic receptor antagonist (+/-)-α-methyl-4-carboxyphenylglycine (MCPG; 100 mm in 50 nl) in the RTN did not affect sympathoexcitatory responses induced by hypercapnia. Injection of DNQX reduced hypercapnia-induced phrenic activation, whereas MCPG did not. In animals with intact carotid chemoreceptors, bilateral injections of AP-5 and DNQX in the RTN reduced increases in MAP, sSND and PND amplitude produced by intravenous injection of NaCN (50 μg kg(-1)). Injection of MCPG in the RTN did not change responses produced by NaCN. These data indicate that RTN ionotropic glutamatergic receptors are involved in the sympathetic and respiratory responses produced by central and peripheral chemoreceptor activation.

  5. Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro

    NASA Technical Reports Server (NTRS)

    Phelan, K. D.; Gallagher, J. P.

    1992-01-01

    We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.

  6. Increased glutamate synaptic transmission in the nucleus raphe magnus neurons from morphine-tolerant rats.

    PubMed

    Bie, Bihua; Pan, Zhizhong Z

    2005-02-09

    Currently, opioid-based drugs are the most effective pain relievers that are widely used in the treatment of pain. However, the analgesic efficacy of opioids is significantly limited by the development of tolerance after repeated opioid administration. Glutamate receptors have been reported to critically participate in the development and maintenance of opioid tolerance, but the underlying mechanisms remain unclear. Using whole-cell voltage-clamp recordings in brainstem slices, the present study investigated chronic morphine-induced adaptations in glutamatergic synaptic transmission in neurons of the nucleus raphe magnus (NRM), a key supraspinal relay for pain modulation and opioid analgesia. Chronic morphine significantly increased glutamate synaptic transmission exclusively in one class of NRM cells that contains mu-opioid receptors in a morphine-tolerant state. The adenylyl cyclase activator forskolin and the cAMP analog 8-bromo-cAMP mimicked the chronic morphine effect in control neurons and their potency in enhancing the glutamate synaptic current was significantly increased in neurons from morphine-tolerant rats. MDL12330a, an adenylyl cyclase inhibitor, and H89, a protein kinase A (PKA) inhibitor, reversed the increase in glutamate synaptic transmission induced by chronic morphine. In addition, PMA, a phorbol ester activator of protein kinase C (PKC), also showed an increased potency in enhancing the glutamate synaptic current in these morphine-tolerant cells. The PKC inhibitor GF109203X attenuated the chronic morphine effect. Taken together, these results suggest that chronic morphine increases presynaptic glutamate release in mu receptor-containing NRM neurons in a morphine-tolerant state, and that the increased glutamate synaptic transmission appears to involve an upregulation of both the cAMP/PKA pathway and the PKC pathway. This glutamate-mediated activation of these NRM neurons that are thought to facilitate spinal pain transmission may contribute to

  7. Light, neurotransmitters and the suprachiasmatic nucleus control of pineal melatonin production in the rat.

    PubMed

    Kennaway, D J

    1997-01-01

    There is considerable interest in the neuronal pathways involved in the generation and entrainment of circadian rhythms. We have monitored the output of the pineal gland via the urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT.6S), following drug treatment to provide information on the transmitters mediating the effects of light. As a check on the specificity of the response [suprachiasmatic nucleus (SCN) versus direct pineal effects] we also monitored in separate experiments c-Fos induction in the SCN in response to the treatments. Administration of the excitatory amino acid (EAA) antagonist MK-801 (3 mg/kg) failed to inhibit either the acute or entraining effects of light on melatonin production and only partially (approximately 30%) prevented the induction of c-Fos in the SCN. These results suggested that EAA are either not important in mediating the effects of light in the rat or that pathways utilising transmitters other than EAA may be involved. When the non-specific serotonin agonist quipazine was administered at CT 18, it mimicked both the acute and phase delaying effects of light on melatonin secretion and induced c-Fos in the SCN with a regional distribution identical to that observed following light treatment. Characterisation of the receptor subtypes involved in this response implicated the 5HT2c receptor on the basis of the response to (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane HCl (DOI, 0.1-0.5 mg/kg) and the potent antagonism by ritanserin and ketanserin. DOI (0.5 mg/kg) also induced c-Fos in the SCN and the induction was prevented by ritanserin and ketanserin. Despite the potency of 5HT2c agonists in mimicking light effects on melatonin rhythmicity, at the time of preparation we have not been able to block the effects of 2-1x/1-min light pulses on the melatonin rhythm with either metergoline (15 mg/kg), ritanserin (3 mg/kg) or ketanserin (3 mg/kg). Similarly ritanserin (10 mg/kg) failed to block light-induced c-Fos induction in

  8. Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats.

    PubMed

    Kitaichi, Yuji; Inoue, Takeshi; Nakagawa, Shin; Boku, Shuken; Kakuta, Aya; Izumi, Takeshi; Koyama, Tsukasa

    2010-11-25

    Selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for depression. Recent reports in the literature describe differences in antidepressant effects among SSRIs. Although each SSRI apparently has different pharmacological actions aside from serotonin reuptake inhibition, the relations between antidepressant effects and unique pharmacological properties in respective SSRIs remain unclear. This study was designed to compare abilities of three systemically administered SSRIs to increase the extracellular levels of serotonin, dopamine, and noradrenaline acutely in three brain regions of male Sprague-Dawley rats. We examined effects of sertraline, fluvoxamine, and paroxetine on extracellular serotonin, dopamine, and noradrenaline levels in the medial prefrontal cortex, nucleus accumbens and striatum of rats using in vivo microdialysis. Dialysate samples were collected in sample vials every 20 min for 460 min. Extracellular serotonin, dopamine, and noradrenaline levels were determined using high-performance liquid chromatography with electrochemical detection. All SSRI administrations increased extracellular serotonin levels in all regions. Only sertraline administration increased extracellular dopamine concentrations in the nucleus accumbens and striatum. All SSRI administrations increased extracellular noradrenaline levels in the nucleus accumbens, although fluvoxamine was less effective. These results suggest that neurochemical differences account for the differences in clinical antidepressant effects among SSRIs. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Ca(2+) in the dorsal raphe nucleus promotes wakefulness via endogenous sleep-wake regulating pathway in the rats.

    PubMed

    Cui, Su-Ying; Li, Sheng-Jie; Cui, Xiang-Yu; Zhang, Xue-Qiong; Yu, Bin; Huang, Yuan-Li; Cao, Qing; Xu, Ya-Ping; Yang, Guang; Ding, Hui; Song, Jin-Zhi; Ye, Hui; Sheng, Zhao-Fu; Wang, Zi-Jun; Zhang, Yong-He

    2016-07-26

    Serotonergic neurons in the dorsal raphe nucleus (DRN) are involved in the control of sleep-wake states. Our previous studies have indicated that calcium (Ca(2+)) modulation in the DRN plays an important role in rapid-eye-movement sleep (REMS) and non-REMS (NREMS) regulation during pentobarbital hypnosis. The present study investigated the effects of Ca(2+) in the DRN on sleep-wake regulation and the related neuronal mechanism in freely moving rats. Our results showed that microinjection of CaCl2 (25 or 50 nmol) in the DRN promoted wakefulness and suppressed NREMS including slow wave sleep and REMS in freely moving rats. Application of CaCl2 (25 or 50 nmol) in the DRN significantly increased serotonin in the DRN and hypothalamus, and noradrenaline in the locus coeruleus and hypothalamus. Immunohistochemistry study indicated that application of CaCl2 (25 or 50 nmol) in the DRN significantly increased c-Fos expression ratio in wake-promoting neurons including serotonergic neurons in the DRN, noradrenergic neurons in the locus coeruleus, and orxinergic neurons in the perifornical nucleus, but decreased c-Fos expression ratio of GABAergic sleep-promoting neurons in the ventrolateral preoptic nucleus. These results suggest that Ca(2+) in the DRN exert arousal effects via up-regulating serotonergic functions in the endogenous sleep-wake regulating pathways.

  10. 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.

  11. Absolute number of parvicellular and magnocellular neurons in the red nucleus of the rat midbrain: a stereological study.

    PubMed

    Aghoghovwia, Benjamin E; Oorschot, Dorothy E

    2016-09-01

    The absolute number of parvicellular and magnocellular neurons in the red nucleus was estimated using design-based stereological counting methods and systematic random sampling techniques. Six young adult male rats, and a complete set of serial 40-μm glycolmethacrylate sections for each rat, were used to quantify neuronal numbers. After a random start, a systematic subset (i.e. every third) of the serial sections was used to estimate the total volume of the red nucleus using Cavalieri's method. The same set of sampled sections was used to estimate the number of neurons in a known subvolume (i.e. the numerical density Nv ) by the optical disector method. Multiplication of the total volume by Nv yielded the absolute number of neurons. It was found that the right red nucleus consisted, on average, of 8400 parvicellular neurons (with a coefficient of variation of 0.16) and 7000 magnocellular neurons (0.12). These total neuronal numbers provide important data for the transfer of information through these nuclei and for species comparisons. © 2016 Anatomical Society.

  12. 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

  13. Role of glutamatergic receptors located in the nucleus raphe magnus on antinociceptive effect of morphine microinjected into the nucleus cuneiformis of rat.

    PubMed

    Haghparast, Abbas; Soltani-Hekmat, Ava; Khani, Abbas; Komaki, Alireza

    2007-10-29

    Neurons in the nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, project to medullary nucleus raphe magnus (NRM), which is a key medullary relay for descending pain modulation and is critically involved in opioid-induced analgesia. Previous studies have shown that antinociceptive response of CnF-microinjected morphine can be modulated by the specific subtypes of glutamatergic receptors within the CnF. In this study, we evaluated the role of NMDA and kainate/AMPA receptors that are widely distributed within the NRM on morphine-induced antinociception elicited from the CnF. Hundred and five male Wistar rats weighing 250-300 g were used. Morphine (10, 20 and 40 microg) and NMDA receptor antagonist, MK-801 (10 microg) or kainate/AMPA receptor antagonist, DNQX (0.5 microg) in 0.5 microl saline were stereotaxically microinjected into the CnF and NRM, respectively. The latency of tail-flick response was measured at set intervals (2, 7, 12, 17, 22, 27 min after microinjection) by using an automated tail-flick analgesiometer. The results showed that morphine microinjection into the CnF dose-dependently causes increase in tail-flick latency (TFL). MK-801 microinjected into the NRM, just 1 min before morphine injection into the CnF, significantly attenuated antinociceptive effects of morphine. On the other hand, DNQX microinjected into the NRM, significantly increased TFL after local application of morphine into the CnF. We suggest that morphine related antinociceptive effect elicited from the CnF is mediated, in part, by NMDA receptor at the level of the NRM whereas kainite/AMPA receptor has a net inhibitory influence at the same pathway.

  14. Electrolytic lesion of the nucleus raphe magnus reduced the antinociceptive effects of bilateral morphine microinjected into the nucleus cuneiformis in rats.

    PubMed

    Haghparast, Abbas; Ordikhani-Seyedlar, Mehdi; Ziaei, Maryam

    2008-06-27

    Several lines of investigation show that the rostral ventromedial medulla is a critical relay for midbrain regions, including the nucleus cuneiformis (CnF), which control nociception at the spinal cord. There is some evidence that local stimulation or morphine administration into the CnF produces the effective analgesia through the nucleus raphe magnus (NRM). The present study tries to determine the effect of morphine-induced analgesia following microinjection into the CnF in the absence of NRM. Seven days after the cannulae implantation, morphine was microinjected bilaterally into the CnF at the doses of 0.25, 1, 2.5, 5, 7.5 and 10 microg/0.3 microl saline per side. The morphine-induced antinociceptive effect measured by tail-flick test at 30, 60, 90 and 120 min after microinjection. The results showed that bilateral microinjection of morphine into the CnF dose-dependently causes increase in tail-flick latency (TFL). The 50% effective dose of morphine was determined and microinjected into the CnF (2.5 microg/0.3 microl saline per side) in rats after NRM electrolytic lesion (1 mA, 30 s). Lesion of the NRM significantly decreased TFLs, 30 (P<0.01) and 60 (P<0.05) but not 90-120 min after morphine microinjection into the CnF, compared with sham-lesion group. We concluded that morphine induces the analgesic effects through the opioid receptors in the CnF. It is also appeared that morphine-induced antinociception decreases following the NRM lesion but it seems that there are some other descending pain modulatory pathways that activate in the absence of NRM.

  15. Cardiovascular response to renin substrate microinjection into the central nucleus of the amygdala of rats.

    PubMed

    Heshmatian, Behnam; Parviz, Mohsen; Karimian, Sayed Morteza; Keshavarz, Mansoor; Sohanaki, Hamid

    2007-05-07

    Central nucleus of the amygdala is involved in cardiovascular regulation. Although most components of the renin-angiotensin system have been found to be distributed in amygdala, renin expression in brain has remained controversial. This work was undertaken to elucidate the extent of renin presence in this nucleus. A cannula was implanted bilaterally into the central nucleus of the amygdala. Mean arterial pressure and heart rate were directly measured via indwelling femoral artery cannula post bilateral intra central nucleus of the amygdala microinjection of renin substrate. Renin substrate microinjection dose-dependently increased mean arterial pressure and heart rate, whereas captopril, saralasin and losartan pretreatment inhibited these effects. The results suggest the presence of local renin or similar proteases in this nucleus.

  16. Dorsal raphe nucleus of brain in the rats flown in space inflight and postflight alteration of structure

    NASA Astrophysics Data System (ADS)

    Krasnov, I.

    The structure of brain dorsal raphe nucleus (DRN) was studied in the rats flown in space aboard Space Shuttle "Columbia" (STS-58, SLS-2 program) and dissected on day 13 of the mission ("inflight" rats) and in 5-6 hours after finishing 14-day flight ("postflight" rats). The brain of "inflight" rats were excised after decapitation, sectioned sagitally halves of brain were fixed by immersion in 2,5 % glutaraldehyde in 0.1 M cacodylate buffer pH 7.3 at 4°C and kept in the flight at 4°C. After landing the brain frontal 0.5 mm sections from DRN area were osmificated and embedded in araldite at NASA ARC. The brains of "postflight": and control rats were underwent to the same procedure. Electronmicroscopical analysis, computer morphometry and glial cell count were performed at Moscow. In DRN neuropil of "inflight" rats the most part of axo-dendritic synapses were surrounded by glia cell processes and had decreased electron density of pre- and postsynaptic membrane and pronounced diminution of synaptic vesicle amount while dendrites were characterized by decrease in matrix electron density and microtubule quantity that in total indicates the decline of afferent flow reaching DRN neurons in microgravity. In DRN neurons of "inflight" rats all mitochondria were characterized by evenly increased dimensions, decreased matrix electron density, small amount of short and far- between located cristae and enlarged intermembrane and intercristae spaces, that in total points out low level of coupling of oxidation to phosphorilation, decrease in energy supply of neuron. Amount of ribosome in cytoplasm was significantly decreased indicating lower lever of biosynthetic processes. The last is supported by diminished dimensions of neuronal body, nucleus and nucleolus (place of r RNA synthesis), cross section area of that were reduced in DRN neurons of "inflight" rats by 18.8 % (p < 0.01), 11.1 % and 26.6 % (p <0,005) correspondingly. Ultrastructure and dimensions of intracellular

  17. Increased expression of proenkephalin and prodynorphin mRNAs in the nucleus accumbens of compulsive methamphetamine taking rats.

    PubMed

    Cadet, Jean Lud; Krasnova, Irina N; Walther, Donna; Brannock, Christie; Ladenheim, Bruce; McCoy, Michael T; Collector, Daniel; Torres, Oscar V; Terry, Ndeah; Jayanthi, Subramaniam

    2016-11-14

    Addiction is associated with neuroadaptive changes in the brain. In the present paper, we used a model of methamphetamine self-administration during which we used footshocks to divide rats into animals that continue to press a lever to get methamphetamine (shock-resistant) and those that significantly reduce pressing the lever (shock-sensitive) despite the shocks. We trained male Sprague-Dawley rats to self-administer methamphetamine (0.1 mg/kg/infusion) for 9 hours daily for 20 days. Control group self-administered saline. Subsequently, methamphetamine self-administration rats were punished by mild electric footshocks for 10 days with gradual increases in shock intensity. Two hours after stopping behavioral experiments, we euthanized rats and isolated nucleus accumbens (NAc) samples. Affymetrix Array experiments revealed 24 differentially expressed genes between the shock-resistant and shock-sensitive rats, with 15 up- and 9 downregulated transcripts. Ingenuity pathway analysis showed that these transcripts belong to classes of genes involved in nervous system function, behavior, and disorders of the basal ganglia. These genes included prodynorphin (PDYN) and proenkephalin (PENK), among others. Because PDYN and PENK are expressed in dopamine D1- and D2-containing NAc neurons, respectively, these findings suggest that mechanisms, which impact both cell types may play a role in the regulation of compulsive methamphetamine taking by rats.

  18. Increased expression of proenkephalin and prodynorphin mRNAs in the nucleus accumbens of compulsive methamphetamine taking rats

    PubMed Central

    Cadet, Jean Lud; Krasnova, Irina N.; Walther, Donna; Brannock, Christie; Ladenheim, Bruce; McCoy, Michael T.; Collector, Daniel; Torres, Oscar V.; Terry, Ndeah; Jayanthi, Subramaniam

    2016-01-01

    Addiction is associated with neuroadaptive changes in the brain. In the present paper, we used a model of methamphetamine self-administration during which we used footshocks to divide rats into animals that continue to press a lever to get methamphetamine (shock-resistant) and those that significantly reduce pressing the lever (shock-sensitive) despite the shocks. We trained male Sprague-Dawley rats to self-administer methamphetamine (0.1 mg/kg/infusion) for 9 hours daily for 20 days. Control group self-administered saline. Subsequently, methamphetamine self-administration rats were punished by mild electric footshocks for 10 days with gradual increases in shock intensity. Two hours after stopping behavioral experiments, we euthanized rats and isolated nucleus accumbens (NAc) samples. Affymetrix Array experiments revealed 24 differentially expressed genes between the shock-resistant and shock-sensitive rats, with 15 up- and 9 downregulated transcripts. Ingenuity pathway analysis showed that these transcripts belong to classes of genes involved in nervous system function, behavior, and disorders of the basal ganglia. These genes included prodynorphin (PDYN) and proenkephalin (PENK), among others. Because PDYN and PENK are expressed in dopamine D1- and D2-containing NAc neurons, respectively, these findings suggest that mechanisms, which impact both cell types may play a role in the regulation of compulsive methamphetamine taking by rats. PMID:27841313

  19. Sex-specific effects of met-enkephalin treatment on vasopressin immunoreactivity in the rat supraoptic nucleus.

    PubMed

    Blanco, E; Carretero, J; Sànchez, F; Riesco, J M; Vàzquez, R

    1989-01-01

    The supraoptic nucleus of male and female rats treated with met-enkephalin or naloxone and met-enkephalin was examined with light microscopical immunocytochemistry for Arginine-vasopressin. Both genders exhibited the same distribution of immunostained magnocellular neurons. Met-enkephalin treatment caused an increase in number of immunostained vasopressin neurons. This effect was more pronounced in females than in males. Naloxone treatment diminished immunoreactive cytoplasmic vasopressin in males more effectively than in females. In enkephalin-treated animals numerous vasopressin immunoreactive varicosities appeared within the supraoptic nucleus, but were mostly absent in naloxone-treated animals and in controls. Our results indicate that met-enkephalin treatment either stimulates vasopressin synthesis or inhibits secretion. It is likely that steroid hormones mediate the action of enkephalin on vasopressin secretion in a specific manner.

  20. Deep brain stimulation of the medial septum or nucleus accumbens alleviates psychosis-relevant behavior in ketamine-treated rats.

    PubMed

    Ma, Jingyi; Leung, L Stan

    2014-06-01

    Deep brain stimulation (DBS) has been shown to be effective for relief of Parkinson's disease, depression and obsessive-compulsive disorder in humans, but the effect of DBS on psychosis is largely unknown. In previous studies, we showed that inactivation of the medial septum or nucleus accumbens normalized the hyperactive and psychosis-related behaviors induced by psychoactive drugs. We hypothesized that DBS of the medial septum or nucleus accumbens normalizes the ketamine-induced abnormal behaviors and brain activity in freely moving rats. Male Long-Evans rats were subcutaneously injected with ketamine (3 mg/kg) alone, or given ketamine and DBS, or injected with saline alone. Subcutaneous injection of ketamine resulted in loss of gating of hippocampal auditory evoked potentials (AEPs), deficit in prepulse inhibition (PPI) and hyperlocomotion, accompanied by increased hippocampal gamma oscillations of 70-100 Hz. Continuous 130-Hz stimulation of the nucleus accumbens, or 100-Hz burst stimulation of the medial septum (1s on and 5s off) significantly attenuated ketamine-induced PPI deficit and hyperlocomotion. Medial septal stimulation also prevented the loss of gating of hippocampal AEPs and the increase in hippocampal gamma waves induced by ketamine. Neither septal or accumbens DBS alone without ketamine injection affected spontaneous locomotion or PPI. The results suggest that DBS of the medial septum or nucleus accumbens may be an effective method to alleviate psychiatric symptoms of schizophrenia. The effect of medial septal DBS in suppressing both hippocampal gamma oscillations and abnormal behaviors induced by ketamine suggests that hippocampal gamma oscillations are a correlate of disrupted behaviors.

  1. Inactivation of the medial mammillary nucleus attenuates theta rhythm activity in the hippocampus in urethane-anesthetized rats.

    PubMed

    Żakowski, Witold; Braszka, Łukasz; Zawistowski, Piotr; Orzeł-Gryglewska, Jolanta; Jurkowlaniec, Edyta

    2017-04-03

    Although the importance of the mammillary body for memory and learning processes is well known, its exact role has remained vague. The fact, that many neurons in one nucleus of the mammillary body in rats, i.e. the medial mammillary nucleus (MM), fires according with hippocampal theta rhythm, makes this structure crucial for a theta rhythm signaling in so-called extended hippocampal system. These neurons are driven by descending projections from the hippocampal formation, but it is still unknown whether the mammillary body only conveys theta rhythm or may also modulate it. In the present study, we investigated the effect of pharmacological inactivation (local infusion of 0.5μl of 20% procaine hydrochloride solution) of the MM on hippocampal theta rhythm in urethane-anesthetized rats. We found that intra-MM procaine microinjections suppress sensory-elicited theta rhythm in the hippocampus by reduction of its amplitude, but not the frequency. Procaine infusion decreased the EEG signal power of low theta frequency bands, i.e. 3-5Hz, down to 9.2% in 3-4Hz band in comparison to pre-injection conditions. After water infusion (control group) no changes of hippocampal EEG signal power were observed. Our findings showed for the first time that inactivation of the MM leads to a disruption of hippocampal theta rhythm in the rat, which may suggest that the mammillary body can regulate theta rhythm signaling in the extended hippocampal system.

  2. Melanin-concentrating hormone inputs to the nucleus accumbens originate from distinct hypothalamic sources and are apposed to GABAergic and cholinergic cells in the Long-Evans rat brain.

    PubMed

    Haemmerle, C A S; Campos, A M P; Bittencourt, J C

    2015-03-19

    Melanin-concentrating hormone [MCH] is a neuropeptide that modulates several behaviors, such as feeding and reward. Because the hedonic and rewarding features of a food also influence feeding behavior, the nucleus accumbens [Acb] has been highlighted as a key area integrating these roles. Functional data confirm that MCH acts on a subdivision of the Acb; however, considering the importance of finding anatomical and neurochemical data that correlate the previously demonstrated function of MCH, we delineated this investigation based on the following points: (1) Is there a pattern of innervation by MCH fibers regarding the subregions within the Acb? (2) Specifically, which hypothalamic nuclei synthesize MCH and innervate the Acb? (3) Finally, what are the neurochemical identities of the accumbal neurons innervated by MCH inputs? We examined the MCH immunoreactivity [MCH-ir] in the Acb in rat brains using the peroxidase technique. Additionally, after injecting retrograde neuronal tracer [Fluoro-Gold® - FG®] into subdivisions of the Acb [shell or core], we mapped single- or double-labeled cells. Moreover, using a double immunoperoxidase protocol, we investigated the MCH-ir fibers for gamma-aminobutyric acid [GABA]-ir and choline acetyltransferase [ChAT]-ir cells in the shell subdivision of the Acb [AcbSh]. We found that the MCH-ir fibers preferentially innervate the medial AcbSh, particularly the septal pole. This innervation originated from the incerto-hypothalamic area [IHy], internuclear area, lateral hypothalamic area, perifornical area, periventricular nucleus and posterior hypothalamus. Moreover, the IHy has the highest relationship between double/single retrogradely labeled cells [n=5.33±0.66/16±0.93, i.e. 33.33%] in the whole hypothalamus. Furthermore, our data suggest that MCH-ir fibers are in apposition to GABAergic and cholinergic cells in the AcbSh. Therefore, we provide anatomical support to the ongoing functional studies investigating the relation

  3. Suprachiasmatic Nucleus and Subparaventricular Zone Lesions Disrupt Circadian Rhythmicity but Not Light-Induced Masking Behavior in Nile Grass Rats.

    PubMed

    Gall, Andrew J; Shuboni, Dorela D; Yan, Lily; Nunez, Antonio A; Smale, Laura

    2016-04-01

    The ventral subparaventricular zone (vSPVZ) receives direct retinal input and influences the daily patterning of activity in rodents, making it a likely candidate for the mediation of acute behavioral responses to light (i.e., masking). We performed chemical lesions aimed at the vSPVZ of diurnal grass rats (Arvicanthis niloticus) using N-methyl-D,L-aspartic acid (NMA), a glutamate agonist. Following NMA lesions, we placed grass rats in various lighting conditions (e.g., 12:12 light-dark, constant dark, constant light); presented a series of light pulses at circadian times (CT) 6, 14, 18, and 22; and placed them in a 7-h ultradian cycle to assess behavioral masking. Extensive bilateral lesions of the vSPVZ disrupted the expression of circadian rhythms of activity and abolished the circadian modulation of masking responses to light, without affecting light-induced masking behavior per se. We also found that in diurnal grass rats, NMA was capable of destroying not only neurons of the vSPVZ but also those of the suprachiasmatic nucleus (SCN), even though excitotoxins have been ineffective at destroying cells within the SCN of nocturnal rodents. The vulnerability of the grass rat's SCN to NMA toxicity raises the possibility of a difference in density of receptors for glutamate between nocturnal and diurnal species. In cases in which damage extended to the SCN, masking responses to light were present and similar to those displayed by animals with damage restricted to the vSPVZ. Thus, extensive bilateral lesions of the SCN and vSPVZ disrupted the expression of circadian rhythms without affecting acute responses to light in a diurnal species. Our present and previous results suggest that retinorecipient brain areas other than the SCN or vSPVZ, such as the intergeniculate leaflet or olivary pretectal nucleus, may be responsible for the mediation of masking responses to light in the diurnal grass rat.

  4. Effects of cochlear ablation on amino acid concentrations in the chinchilla posteroventral cochlear nucleus, as compared to rat.

    PubMed

    Godfrey, D A; Chen, K; Godfrey, M A; Jin, Y-M; Robinson, K T; Hair, C

    2008-06-12

    Using a microchemical approach, we measured changes of amino acid concentrations in the chinchilla caudal posteroventral cochlear nucleus (PVCN) after cochlear ablation to determine to what extent slow decreases of glutamate and aspartate concentrations after carboplatin treatment resulted from slower effects of cochlear damage in chinchillas than in rats and guinea pigs, as opposed to effects of carboplatin treatment being slower than those of cochlear ablation. Our results indicate that both factors are involved: decreases of glutamate and aspartate concentrations after cochlear ablation are much slower in chinchillas than in rats and guinea pigs, but they are much faster than the decreases after carboplatin treatment. Further, aspartate and glutamate concentrations in the chinchilla caudal PVCN decreased by larger amounts after cochlear ablation than in rats or guinea pigs, and there was a transient increase of aspartate concentration at short survival times. Detailed mapping of amino acid concentrations in the PVCN of a chinchilla with 1 month survival after cochlear ablation and a rat with 7 days' survival indicated that the reductions of glutamate and aspartate occurred throughout the PVCN but were somewhat larger in ventral and caudal parts in chinchilla. Any decreases in the adjacent granular region were very small. There were also sustained bilateral decreases in concentrations of other amino acids, notably GABA and glycine, in the caudal PVCN of cochlea-ablated chinchillas but not rats. The effects of cochlear ablation on the concentrations of most of these other amino acids in chinchilla caudal PVCN differed from those of carboplatin treatment. Thus, although a major effect of auditory nerve damage on the cochlear nucleus-decreases of glutamate and aspartate concentrations-occurs across species and types of lesions, the details of timing and magnitude and the effects on other amino acids can vary greatly.

  5. High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat.

    PubMed

    Hume, Catherine; Sabatier, Nancy; Menzies, John

    2017-07-01

    Oxytocin is a potent anorexigen and is believed to have a role in satiety signaling. We developed rat models to study the activity of oxytocin neurons in response to voluntary consumption or oral gavage of foods using c-Fos immunohistochemistry and in vivo electrophysiology. Using c-Fos expression as an indirect marker of neural activation, we showed that the percentage of magnocellular oxytocin neurons expressing c-Fos increased with voluntary consumption of sweetened condensed milk (SCM). To model the effect of food in the stomach, we gavaged anesthetized rats with SCM. The percentage of supraoptic nucleus and paraventricular nucleus magnocellular oxytocin-immunoreactive neurons expressing c-Fos increased with SCM gavage but not with gastric distention. To further examine the activity of the supraoptic nucleus, we made in vivo electrophysiological recordings from SON neurons, where anesthetized rats were gavaged with SCM or single cream. Pharmacologically identified oxytocin neurons responded to SCM gavage with a linear, proportional, and sustained increase in firing rate, but cream gavage resulted in a transient reduction in firing rate. Blood glucose increased after SCM gavage but not cream gavage. Plasma osmolarity and plasma sodium were unchanged throughout. We show that in response to high-sugar, but not high-fat, food in the stomach, there is an increase in the activity of oxytocin neurons. This does not appear to be a consequence of stomach distention or changes in osmotic pressure. Our data suggest that the presence of specific foods with different macronutrient profiles in the stomach differentially regulates the activity of oxytocin neurons. Copyright © 2017 Endocrine Society.

  6. Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats

    PubMed Central

    Machado, Andre G.; Baker, Kenneth B.; Schuster, Daniel; Butler, Robert S.; Rezai, Ali

    2009-01-01

    Novel neurorehabilitative strategies are needed to improve motor outcomes following stroke. Based on the disynaptic excitatory projections of the dentatothalamocortical pathway to the motor cortex as well as anterior and posterior cortical areas, we hypothesize that chronic electrical stimulation of the contralesional dentate (lateral cerebellar) nucleus output can enhance motor recovery after ischemia via augmentation of perilesional cortical excitability. Seventy five Wistar rats were pre-trained in the Montoya staircase task and subsequently suffered left cerebral ischemia with the 3-vessel occlusion model. All survivors underwent stereotactic right lateral cerebellar nucleus (LCN) implantation of bipolar electrodes. Rats were then randomized to 4 groups: LCN stimulation at 10 pps, 20 pps, 50 pps or sham stimulation, which was delivered for a period of six weeks. Performance on the Montoya task was re-assessed over the last four weeks of the stimulation period. On the right (contralesional) side, motor performance of the groups undergoing sham, 10 pps, 20 pps and 50 pps stimulation was, respectively, 2.5± 2.7; 2.1 ± 2.5; 6.0 ± 3.9 (p<0.01) and 4.5 ± 3.5 pellets. There was no difference on the left (ipsilesional) side motor performance among the sham or stimulation groups, varying from 15.9 ± 6.7 to 17.2 ± 2.1 pellets. We conclude that contralesional chronic electrical stimulation of the lateral cerebellar nucleus at 20 pps but not at 10 or 50 pps improves motor recovery in rats following ischemic strokes. This effect is likely to be mediated by increased perilesional cortical excitability via chronic activation of the dentatothalamocortical pathway. PMID:19445910

  7. Interleukin-1 Inhibits Putative Cholinergic Neurons in Vitro and REM Sleep when Microinjected into the Rat Laterodorsal Tegmental Nucleus

    PubMed Central

    Brambilla, Dario; Barajon, Isabella; Bianchi, Susanna; Opp, Mark R.; Imeri, Luca

    2010-01-01

    Study Objectives: REM sleep is suppressed during infection, an effect mimicked by the administration of cytokines such as interleukin-1 (IL-1). In spite of this observation, brain sites and neurochemical systems mediating IL-1-induced suppression of REM sleep have not been identified. Cholinergic neurons in the brainstem laterodorsal tegmental nucleus (LDT) are part of the neuronal circuitry responsible for REM sleep generation. Since IL-1 inhibits acetylcholine synthesis and release, the aim of this study was to test the two different, but related hypotheses. We hypothesized that IL-1 inhibits LDT cholinergic neurons, and that, as a result of this inhibition, IL-1 suppresses REM sleep. Design, Measurement, and Results: To test these hypotheses, the electrophysiological activity of putative cholinergic LDT neurons was recorded in a rat brainstem slice preparation. Interleukin-1 significantly inhibited the firing rate of 76% of recorded putative cholinergic LDT neurons and reduced the amplitude of glutamatergic evoked potentials in 60% of recorded neurons. When IL-1 (1 ng) was microinjected into the LDT of freely behaving rats, REM sleep was reduced by about 50% (from 12.7% ± 1.5% of recording time [after vehicle] to 6.1% ± 1.4% following IL-1 administration) during post-injection hours 3-4. Conclusions: Results of this study support the hypothesis that IL-1 can suppress REM sleep by acting at the level of the LDT nucleus. Furthermore this effect may result from the inhibition of evoked glutamatergic responses and of spontaneous firing of putative cholinergic LDT neurons. Citation: Brambilla D; Barajon I; Bianchi S; Opp MR; Imeri L. Interleukin-1 inhibits putative cholinergic neurons in vitro and REM sleep when microinjected into the rat laterodorsal tegmental nucleus. SLEEP 2010;33(7):919-929. PMID:20614852

  8. Renal Denervation Improves Exaggerated Sympathoexcitation in Rats with Heart Failure: A Role for nNOS in the Paraventricular Nucleus

    PubMed Central

    Patel, Kaushik P.; Xu, Bo; Liu, Xuefei; Sharma, Neeru M.; Zheng, Hong

    2016-01-01

    Renal denervation (RDN) has been postulated to reduce sympathetic drive during heart failure (HF), but the central mechanisms are not completely understood. The purpose of the present study was to assess the contribution of neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus (PVN) in modulating sympathetic outflow in rats with HF that underwent RDN. HF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, bilateral RDN was performed. Rats with HF had an increase in FosB-positive cells in the PVN with a concomitant increase in urinary excretion of norepinephrine and both of these parameters were ameliorated after RDN. nNOS-positive cells immunostaining, diaphorase staining, and nNOS protein expression were significantly decreased in the PVN of HF rats, findings that were ameliorated by RDN. Microinjection of nNOS inhibitor L-NMMA into the PVN resulted in a blunted increase in lumbar sympathetic nerve activity (ΔLSNA: 11 ± 2 vs. 24 ± 2%) in HF than in sham group. This response was normalized after RDN. Stimulation of afferent renal nerve (ARN) produced a greater activation of PVN neurons in rats with HF. ARN stimulation elicited a greater increase in LSNA in rats with HF compared to sham rats (ΔLSNA: 45 ± 5 vs. 22 ± 2%). These results suggest that intact renal nerves contribute to the reduction of nNOS in the PVN, resulting in activation of the neurons in the PVN of rats with HF. RDN restores nNOS and thus attenuates the sympathoexcitation commonly observed in HF. PMID:27185748

  9. Hyperventilation evoked by activation of the vicinity of the caudal inferior olivary nucleus depends on the fastigial nucleus in anesthetized rats.

    PubMed

    Zhuang, Jianguo; Xu, Fadi; Frazier, Donald T

    2008-05-01

    Several studies have demonstrated that cerebellar deep nuclei, particularly the rostral fastigial nucleus (FNr), are involved in respiratory modulation. These nuclei receive inputs from the contralateral caudal inferior olivary nuclei of the medulla. The objectives of this study were to determine whether electrical and chemical activation of the vicinity of the caudal inferior olivary nuclei (vIOc) affected respiration and, if true, whether the FNr was involved in the vIOc stimulation-evoked ventilatory responses. Experiments were conducted in 30 anesthetized and spontaneously breathing rats. Our results showed that 1) electrical (25 or 100 microA at 10 or 20 Hz for 10 s) and chemical (1 or 100 mM, 25-50 nl N-methyl-D-aspartate) stimulation of the vIOc augmented ventilation predominantly via increasing tidal volume; 2) the responses to the electrical stimulation were almost eliminated by lesion of the contralateral FNr via microinjection of ibotenic acid; and 3) the respiratory responses to electrical stimulation in the vicinity of the rostral IO were 65-70% smaller compared with that evoked by vIOc stimulation. These findings strongly suggest that vIOc neurons play a significant role in modulation of respiratory activity, largely depending on their projections to the FNr.

  10. Corticosterone microinjected into nucleus pontis oralis increases tonic immobility in rats.

    PubMed

    Sandoval-Herrera, Vicente; Trujillo-Ferrara, José G; Miranda-Páez, Abraham; De La Cruz, Fidel; Zamudio, Sergio R

    2011-09-01

    Tonic immobility (TI) is also known as "immobility response", "immobility reflex", "animal hypnosis", etc. It is an innate antipredatory behavior characterized by an absence of movement, varying degrees of muscular activity, and a relative unresponsiveness to external stimuli. Experimentally, TI is commonly produced by manually forcing an animal into an inverted position and restraining it in that position until the animal becomes immobile. Part of the neural mechanism(s) of TI involves the medullo-pontine reticular formation, with influence from other components of the brain, notably the limbic system. It has been observed that TI is more prolonged in stressed animals, and systemic injection of corticosterone (CORT) also potentiates this behavior. At present, the anatomical brain regions involved in the CORT modulation of TI are unknown. Thus, our study was made to determine if some pontine areas could be targets for the modulation of TI by CORT. A unilateral nucleus pontis oralis (PnO) microinjection of 1 μL of CORT (0.05 μg/1 μL) in rats resulted in clear behavioral responses. The animals had an increased duration of TI caused by clamping the neck (in this induction, besides of body inversion and restraint, there is also clamping the neck), with an enhancement in open-field motor activity, which were prevented by pretreatment injection into PnO with 1 μL of the mineralocorticoid-receptor antagonist spironolactone (0.5 μg/1 μL) or 1 μL of the glucocorticoid-receptor antagonist mifepristone (0.5 μg/1 μL). In contrast, these behavioral changes were not seen when CORT (0.05 μg/1 μL) was microinjected into medial lemniscus area or paramedian raphe. Our data support the idea that, in stressful situations, glucocorticoids released from adrenals of the prey reach the PnO to produce a hyper arousal state, which in turn can prolong the duration of TI. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Participation of thalamic nuclei in the elaboration of conditioned avoidance reflexes of rats. V. Lesions of the nucleus mediodorsalis.

    PubMed

    Klingberg, F; Klingberg, H

    1978-01-01

    Hooded rats of the Long-Evans strain with isolated bilateral lesions of the nucleus mediodorsalis thalami (MD) were not able to avoid foot-shocks in a simple runway and in the jumping test. They even did not move and showed no emotional reactions during the conditioned stimulus. The lesions did not change spontaneous behaviour, motor patterns or the thresholds of pain reactivity. The animals displayed less spontaneous and goal-directed orienting responses. The possible participation of MD in a functional system realizing certain kinds of prognosis is discussed.

  12. Up-regulation of cocaine- and amphetamine-regulated transcript (CART) in the rat nucleus accumbens after repeated electroconvulsive shock.

    PubMed

    Roh, Myoung-Sun; Cui, Feng Ji; Ahn, Yong Min; Kang, Ung Gu

    2009-10-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide regulates appetite, reward, and mood. CART expression is regulated via the protein kinase A (PKA) pathway, and electroconvulsive shock (ECS), an efficient antipsychotic and antidepressant measure, activates PKA-related signaling. Thus, we hypothesized that ECS may regulate the expression of CART. ECS given daily for five consecutive days increased CART mRNA and protein in the rat nucleus accumbens (NAc), accompanied by an increase in CREB phosphorylation. Our results suggest that ECS-induced CART up-regulation might be associated with PKA-CREB signaling, but the causal direction remains to be elucidated in future studies.

  13. Variable effects of parabrachial nucleus lesions on salt appetite in rats depending upon experimental paradigm and saline concentration.

    PubMed

    Stricker, Edward M; Grigson, Patricia S; Norgren, Ralph

    2013-04-01

    Previous studies have demonstrated that bilateral lesions of the gustatory (medial) zone of the parabrachial nucleus (PBN) in the pons eliminate the salt (sodium chloride; NaCl) appetite induced in rats by treatment with the diuretic drug, furosemide. The present studies reexamined NaCl intake of rats with PBN lesions induced by ibotenic acid, using multiple models of salt appetite. The impairment of a conditioned taste aversion, an established consequence of PBN damage, was used as an initial screen with which to assess the effectiveness of the lesions. Rats with PBN lesions did not drink either 0.3 of a molar (M) solution of NaCl or 0.5 M NaCl in response to daily treatment with desoxycorticosterone acetate. These findings suggest that the excitatory stimulus of salt appetite mediated by mineralocorticoids is abolished by PBN lesions. In contrast, rats with PBN lesions drank some 0.5 M NaCl and more 0.3 M NaCl, in addition to water, in response to hypovolemia induced by subcutaneous injection of 30% polyethylene glycol solution. Those findings suggest that an excitatory stimulus of salt appetite, presumably mediated by Angiotensin II, is not abolished by PBN lesions. These and other observations indicate that lesions of the gustatory PBN in rats may or may not eliminate salt appetite, depending on which model is used and which concentration of NaCl solution is available.

  14. [Chinese herbal medicine enhances sexual function and c-Fos/nNOS expression in the nucleus accumbens of orchidectomized rats].

    PubMed

    Liu, Hongyu; Cui, Jianmei; Zhai, Haifeng; Xue, Jinjuan; Wang, Xiaoyang

    2016-06-01

    There was a decrease in accessory genital organ weight, plasma testosterone, and sexual behavior, as well as a low number of c-Fos-positive cells and a large nNOS-positive cell area in orchidectomized rats. Administration of the herbal medicine increased accessory genital organ weight, testosterone level, mating behavior, and c-Fos-positive cell number, while it decreased the nNOS-positive cell area in orchidectomized rats. An increase of plasma testosterone after administration of "kidney-nourishing" herbal medicine might contribute to the elevated sexual function and activity in orchidectomized rats. In addition, a central nervous system mechanism, such as the functional alteration of NAc, might be involved. Abstract To determine whether the central nervous system is involved in the effect of Chinese herbal medicine on sexual function recovery in orchidectomized rats. Orchidectomized rats were administered intragastrically with a decoction of "kidney-nourishing" Chinese herbal medicine once per day for 28 days. Accessory genital organ weight, plasma testosterone, and mating behavior were investigated. The expression of c-Fos and neuronal nitric oxide synthase (nNOS) in neuronal cells in the nucleus accumbens (NAc) was analyzed by immunohistochemistry.

  15. Differential gene expression in the nucleus accumbens and frontal cortex of lewis and Fischer 344 rats relevant to drug addiction.

    PubMed

    Higuera-Matas, A; Montoya, G L; Coria, S M; Miguéns, M; García-Lecumberri, C; Ambrosio, E

    2011-03-01

    Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism.These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse.

  16. The medial prefrontal cortex and nucleus accumbens mediate the motivation for voluntary wheel running in the rat.

    PubMed

    Basso, Julia C; Morrell, Joan I

    2015-08-01

    Voluntary wheel running in rats provides a preclinical model of exercise motivation in humans. We hypothesized that rats run because this activity has positive incentive salience in both the acquisition and habitual stages of wheel running and that gender differences might be present. Additionally, we sought to determine which forebrain regions are essential for the motivational processes underlying wheel running in rats. The motivation for voluntary wheel running in male and female Sprague-Dawley rats was investigated during the acquisition (Days 1-7) and habitual phases (after Day 21) of running using conditioned place preference (CPP) and the reinstatement (rebound) response after forced abstinence, respectively. Both genders displayed a strong CPP for the acquisition phase and a strong rebound response to wheel deprivation during the habitual phase, suggesting that both phases of wheel running are rewarding for both sexes. Female rats showed a 1.5 times greater rebound response than males to wheel deprivation in the habitual phase of running, while during the acquisition phase, no gender differences in CPP were found. We transiently inactivated the medial prefrontal cortex (mPFC) or the nucleus accumbens (NA), hypothesizing that because these regions are involved in the acquisition and reinstatement of self-administration of both natural and pharmacological stimuli, they might also serve a role in the motivation to wheel run. Inactivation of either structure decreased the rebound response in the habitual phase of running, demonstrating that these structures are involved in the motivation for this behavior. (c) 2015 APA, all rights reserved).

  17. Variable effects of parabrachial nucleus lesions on salt appetite in rats depending upon experimental paradigm and saline concentration

    PubMed Central

    Stricker, Edward M.; Grigson, Patricia S.; Norgren, Ralph

    2014-01-01

    Previous studies have demonstrated that bilateral lesions of the gustatory (medial) zone of the parabrachial nucleus (PBN) in the pons eliminate the salt appetite induced in rats by treatment with the diuretic drug, furosemide. The present studies re-examined NaCl intake of rats with PBN lesions induced by ibotenic acid, using multiple models of salt appetite. The impairment of a conditioned taste aversion, an established consequence of PBN damage, was used as an initial screen with which to assess the effectiveness of the lesions. Rats with PBN lesions did not drink either 0.3 M NaCl or 0.5 M NaCl in response to daily treatment with desoxycorticosterone acetate. These findings suggest that the excitatory stimulus of salt appetite mediated by mineralocorticoids is abolished by PBN lesions. In contrast, rats with PBN lesions drank some 0.5 M NaCl, and more 0.3 M NaCl, in addition to water in response to hypovolemia induced by subcutaneous injection of 30% polyethylene glycol solution. Those findings suggest that an excitatory stimulus of salt appetite, presumably mediated by angiotensin II, is not abolished by PBN lesions. These and other observations indicate that lesions of the gustatory PBN in rats may or may not eliminate salt appetite, depending on which model is used and which concentration of NaCl solution is available. PMID:23398436

  18. Differential Gene Expression in the Nucleus Accumbens and Frontal Cortex of Lewis and Fischer 344 Rats Relevant to Drug Addiction

    PubMed Central

    Higuera-Matas, A; Montoya, G. L; Coria, S.M; Miguéns, M; García-Lecumberri, C; Ambrosio, E

    2011-01-01

    Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism. These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse. PMID:21886580

  19. Cardiovascular effects of microinjection of atrial natriuretic factor (ANF) in the nucleus tractus solitarii of spontaneously hypertensive rats.

    PubMed

    Ermirio, R; Ruggeri, P; Cogo, C E; Picchio, V; Calaresu, F R

    1994-12-01

    The effects on mean arterial pressure (MAP) and heart rate (HR) of unilateral microinjections of atrial natriuretic factor (ANF) into discrete sites of the nucleus tractus solitarii (NTS) of spontaneously hypertensive rats (SHR) were compared with those observed in normotensive Wistar-Kyoto rats (WKY). NTS sites were identified to be involved in cardiovascular control on the basis of the bradycardia and hypotension elicited by microinjections of 20 nl of 0.1 M L-glutamate. Microinjection of 20 nl of 10(-7) M ANF into 38 NTS 'cardiovascular sites' in rats of the SHR strain decreased MAP (-8.7 +/- 1.8 mmHg) and HR (-7.8 +/- 1.9 bpm) in 9 sites (24%), but caused no changes in the remaining 29 sites (76%). In WKY rats 35 cardiovascular sites within the NTS were studied. In 18 sites (51%) ANF microinjections induced a decrease in MAP (-15.1 +/- 1.9 mmHg) and in HR (-18.1 +/- 3.9 bpm), whereas the remaining 17 sites (49%) were unaffected. The decreased responsiveness of the NTS to ANF in the SHR animals could play a role in the development and/or maintenance of the elevated arterial blood pressure in genetically hypertensive rats.

  20. Protein Kinase A in the Pedunculopontine Tegmental Nucleus of Rat Contributes to Regulation of Rapid Eye Movement Sleep

    PubMed Central

    Datta, Subimal; Desarnaud, Frank

    2012-01-01

    Intracellular signaling mechanisms within the pedunculopontine tegmental (PPT) nucleus for the regulation of recovery rapid eye movement (REM) sleep following REM sleep deprivation remain unknown. This study was designed to determine the role of PPT intracellular cAMP-dependent protein kinase A (cAMP-PKA) in the regulation of recovery REM sleep in freely moving rats. The results show that a brief period (3 h) of selective REM sleep deprivation caused REM sleep rebound associated with increased PKA activity and expression of the PKA catalytic subunit protein (PKA-CU) in the PPT. Local application of a cAMP-PKA-activation-selective inhibitor, RpCAMPS (0.55, 1.1, and 2.2 nmol/100 µl; n = 8 rats/group), bilaterally into the PPT, reduced PKA activity and PKA-CU expression in the PPT, and suppressed the recovery REM sleep, in a dose-dependent manner. Regression analyses revealed significant positive relationships between: PPT levels of PKA activity and the total percentages of REM sleep recovery (Rsqr = 0.944; n = 40 rats); PPT levels of PKA-CU expression and the total percentages of REM sleep recovery (Rsqr = 0.937; n = 40 rats); PPT levels of PKA-CU expression and PKA activity (Rsqr = 0.945; n = 40 rats). Collectively, these results provide evidence that activation of intracellular PKA in the PPT contributes to REM sleep recovery following REM sleep deprivation. PMID:20844122

  1. Antinociceptive role of oxytocin in the nucleus raphe magnus of rats, an involvement of mu-opioid receptor.

    PubMed

    Wang, Jing-Wen; Lundeberg, Thomas; Yu, Long-Chuan

    2003-10-15

    Recent studies showed that oxytocin plays an important role in nociceptive modulation in the central nervous system. The present study was undertaken to investigate the role of oxytocin in antinociception in the nucleus raphe magnus (NRM) of rats and the possible interaction between oxytocin and the opioid systems. Intra-NRM injection of oxytocin induced dose-dependent increases in hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulation in rats. The antinociceptive effect of oxytocin was significantly attenuated by subsequent intra-NRM injection of the oxytocin antagonist 1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin. Intra-NRM injection of naloxone dose-dependently antagonized the increased HWLs induced by preceding intra-NRM injection of oxytocin, indicating an involvement of opioid receptors in oxytocin-induced antinociception in the NRM of rats. Furthermore, the antinociceptive effect of oxytocin was dose-dependently attenuated by subsequent intra-NRM injection of the mu-opioid antagonist beta-funaltrexamine (beta-FNA), but not by the kappa-opioid antagonist nor-binaltorphimine (nor-BNI) or the delta-opioid antagonist naltrindole. The results demonstrated that oxytocin plays an antinociceptive role in the NRM of rats through activating the oxytocin receptor. Moreover, mu-opioid receptors, not kappa and delta receptors, are involved in the oxytocin-induced antinociception in the NRM of rats.

  2. GABAergic mechanisms in the nucleus accumbens septi regulating rat motor activity: the effect of chronic treatment with desipramine.

    PubMed

    Płaznik, A; Stefański, R; Kostowski, W

    1990-07-01

    The influence of chronic treatment with desipramine upon GABAergic mechanisms within the nucleus accumbens septi (NAS) affecting rat motor behavior was studied in the automatic open fields. It was shown that intra-accumbens injections of picrotoxin on one hand and muscimol and baclofen on the other, produced dose-dependent increase or decrease in rat motility, respectively. Locomotor stimulation usually observed after picrotoxin did not occur in rats given local injections of a solution containing both picrotoxin and GABA A receptor agonist muscimol. Muscimol (130 ng as a pure compound) blocked also hypermotility produced by intra-accumbens administration of dopamine releasing drug d-amphetamine (10 micrograms). This part of the experiment was summarized as indicating that both GABA A and GABA B receptor-related mechanisms, which are under negative control of dopaminergic neurons in the NAS, play an important role in regulating behavior in the rat. In the second part of the experiment it was observed that chronic treatment of rats with desipramine (DMI) (10 mg/kg, PO, twice daily for 21 days, rats were tested 24 hr after the last dose of the drug) significantly attenuated or blocked the inhibitory effect on locomotion of both baclofen and muscimol. The stimulatory influence of picrotoxin seemed also to be diminished, but it still attained the level of accepted statistical significance. On the basis of these and other data it is concluded that observed changes in the effects of GABAergic agonists in DMI-treated rats are probably due to an enhancement of local dopaminergic mechanisms, thus leading to the potentiation of a negative interaction between dopaminergic and GABAergic mechanisms within the NAS.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Endogenous hydrogen peroxide in paraventricular nucleus mediates sympathetic activation and enhanced cardiac sympathetic afferent reflex in renovascular hypertensive rats.

    PubMed

    Xu, Yao; Gao, Qing; Gan, Xian-Bing; Chen, Lei; Zhang, Lei; Zhu, Guo-Qing; Gao, Xing-Ya

    2011-12-01

    An enhancement of the cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation in renovascular hypertension. Angiotensin II in the paraventricular nucleus (PVN) augments the CSAR and increases sympathetic outflow and blood pressure. The present study aimed to determine whether endogenous hydrogen peroxide in the PVN mediated the enhanced CSAR, sympathetic activity and the effects of angiotensin II in the PVN in renovascular hypertension induced by the two-kidney, one-clip method (2K1C) in rats. At the end of the fourth week, the rats underwent sino-aortic and vagal denervation under general anaesthesia with urethane and α-chloralose. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin. Microinjection of polyethylene glycol-catalase (PEG-CAT), an analogue of endogenous catalase, into the PVN decreased the RSNA and MAP and abolished the CSAR in both sham-operated and 2K1C rats. Microinjection into the PVN of the catalase inhibitor, aminotriazole, increased the RSNA and MAP and enhanced the CSAR. The effects of PEG-CAT or aminotriazole were greater in 2K1C rats than in sham-operated animals. The effects of angiotensin II in the PVN were abolished by pretreatment with PEG-CAT in both sham-operated and 2K1C rats; however, aminotriazole failed to potentiate the effects of angiotensin II. The catalase activity was decreased but the H(2)O(2) levels were increased in the PVN of 2K1C rats. These results indicate that endogenous H(2)O(2) in the PVN not only mediates the enhanced sympathetic activity and CSAR, but also the effects of angiotensin II in the PVN in renovascular hypertensive rats.

  4. Environmental enrichment alters protein expression as well as the proteomic response to cocaine in rat nucleus accumbens

    PubMed Central

    Lichti, Cheryl F.; Fan, Xiuzhen; English, Robert D.; Zhang, Yafang; Li, Dingge; Kong, Fanping; Sinha, Mala; Andersen, Clark R.; Spratt, Heidi; Luxon, Bruce A.; Green, Thomas A.

    2014-01-01

    Prior research demonstrated that environmental enrichment creates individual differences in behavior leading to a protective addiction phenotype in rats. Understanding the mechanisms underlying this phenotype will guide selection of targets for much-needed novel pharmacotherapeutics. The current study investigates differences in proteome expression in the nucleus accumbens of enriched and isolated rats and the proteomic response to cocaine self-administration using a liquid chromatography mass spectrometry (LCMS) technique to quantify 1917 proteins. Results of complementary Ingenuity Pathways Analyses (IPA) and gene set enrichment analyses (GSEA), both performed using protein quantitative data, demonstrate that cocaine increases vesicular transporters for dopamine and glutamate as well as increasing proteins in the RhoA pathway. Further, cocaine regulates proteins related to ERK, CREB and AKT signaling. Environmental enrichment altered expression of a large number of proteins implicated in a diverse number of neuronal functions (e.g., energy production, mRNA splicing, and ubiquitination), molecular cascades (e.g., protein kinases), psychiatric disorders (e.g., mood disorders), and neurodegenerative diseases (e.g., Huntington's and Alzheimer's diseases). Upregulation of energy metabolism components in EC rats was verified using RNA sequencing. Most of the biological functions and pathways listed above were also identified in the Cocaine X Enrichment interaction analysis, providing clear evidence that enriched and isolated rats respond quite differently to cocaine exposure. The overall impression of the current results is that enriched saline-administering rats have a unique proteomic complement compared to enriched cocaine-administering rats as well as saline and cocaine-taking isolated rats. These results identify possible mechanisms of the protective phenotype and provide fertile soil for developing novel pharmacotherapeutics. Proteomics data are available via

  5. Spinal direct current stimulation modulates the activity of gracile nucleus and primary somatosensory cortex in anaesthetized rats

    PubMed Central

    Aguilar, J; Pulecchi, F; Dilena, R; Oliviero, A; Priori, A; Foffani, G

    2011-01-01

    Abstract Afferent somatosensory activity from the spinal cord has a profound impact on the activity of the brain. Here we investigated the effects of spinal stimulation using direct current, delivered at the thoracic level, on the spontaneous activity and on the somatosensory evoked potentials of the gracile nucleus, which is the main entry point for hindpaw somatosensory signals reaching the brain from the dorsal columns, and of the primary somatosensory cortex in anaesthetized rats. Anodal spinal direct current stimulation (sDCS) increased the spontaneous activity and decreased the amplitude of evoked responses in the gracile nucleus, whereas cathodal sDCS produced the opposite effects. At the level of the primary somatosensory cortex, the changes in spontaneous activity induced by sDCS were consistent with the effects observed in the gracile nucleus, but the changes in cortical evoked responses were more variable and state dependent. Therefore, sDCS can modulate in a polarity-specific manner the supraspinal activity of the somatosensory system, offering a versatile bottom-up neuromodulation technique that could potentially be useful in a number of clinical applications. PMID:21825031

  6. Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats.

    PubMed

    Aréchiga-Ceballos, F; Alvarez-Salas, E; Matamoros-Trejo, G; Amaya, M I; García-Luna, C; de Gortari, P

    2014-04-01

    Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus-pituitary-thyroid axis (HPT) is reduced, whereas that of the hypothalamus-pituitary-adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2-3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed by in situ hybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.

  7. Periventricular leukomalacia and prenatal methamphetamine exposure: a case report.

    PubMed

    Murphy, Cary R; Bell, Edward F; Sato, Yutaka; Klein, Jonathan M

    2007-02-01

    Periventricular leukomalacia (PVL) is a complication of prematurity that carries a high risk of long-term neurologic morbidity. We report the first case, to our knowledge, of unexpected PVL associated with in utero methamphetamine exposure in a 30-week gestation premature infant with a benign hospital course, who subsequently developed cerebral palsy by 24 months of life.

  8. Altered nestin expression in the cerebrum with periventricular leukomalacia.

    PubMed

    Okoshi, Yumi; Mizuguchi, Masashi; Itoh, Masayuki; Oka, Akira; Takashima, Sachio

    2007-03-01

    Nestin is a cytoskeletal protein expressed by neural stem cells, and by immature neurons and glial cells. In an effort to explore the potential of the infant brain for repair and plasticity, we immunohistochemically studied nestin expression in the human cerebral cortex of control subjects and of patients with periventricular leukomalacia. During normal development, nestin immunoreactivity of the cortical gray and white matter was detectable throughout the fetal period, and disappeared around birth. In brain with periventricular leukomalacia, nestin expression was altered in a time- and space-dependent manner. In the cortical gray matter, neuronal immunoreactivity was often reduced in the subacute stage, but was increased in chronic and remote stages. In the white matter near a lesion of periventricular leukomalacia, glial immunoreactivity was increased in all stages. In many cases, neurons and axons far from a lesion also showed an altered expression of nestin. These findings indicate that in brain with periventricular leukomalacia, neurons and glial cells may recapitulate nestin expression in response to ischemic brain injury, suggesting functional relevance in repair and plasticity.

  9. Early Language and Communicative Abilities of Children with Periventricular Leukomalacia.

    ERIC Educational Resources Information Center

    Feldman, Heidi M.; And Others

    1992-01-01

    Ten two-year-old children with periventricular leukomalacia (PVL), a brain injury associated with prematurity, were evaluated using language samples. The five children with delayed cognitive ability produced significantly fewer lexical tokens and spontaneous verbal utterances than did chronological age-matched nondelayed PVL children. (Author/DB)

  10. [Influence of ionizing radiation on enzymatic activity and state of nucleus-nucleolar apparatus in rat hepatocytes].

    PubMed

    Nersesova, L S; Gazariants, M G; Mkrtchian, Z S; Meliksetian, G O; Pogosian, L G; Pogosian, S A; Pogosian, L L; Karalova, E M; Avetisian, A S; Abroian, l O; Karalian, Z A; Akopian, Zh I

    2013-01-01

    The effects of a single exposure of rats to the whole-body roentgen irradiation at the doses of 3.5 Gy and 4.5 Gy on the activity of creatine kinase, purine nucleoside phosphorylase, alanine aminotransferase, aspartate aminotransferase, as well as on the state of the nuclear-nucleolar apparatus in rat hepatocytes on the 6th and 13th days after radiation exposure have been studied. Irradiation at the above doses induced changes in the levels of enzymatic activity of different values and different directions within the same time periods, as well as oscillating changes in this type of enzymatic activity over time. This demonstrates various radiosensitivity and adaptation abilities of these enzymatic activities. The changes in the enzymatic activity significantly correspond to the changes in the morphometric indices of nuclear-nucleolar apparatus of hepatocytes, as well as the distribution of hepatocytes within the ploidy classes: in particular, stabilization of the enzymatic activity on the 13th day after irradiation correlates with the increased transcriptional activity, which is detectable through the increased number of nucleoli per nucleus and the expanded space of a hepatocyte nucleus. The compensation mechanisms are likely to be targeted at the changes in the functional activity of surviving hepatocytes, rather than at the replacement of the damaged cells by the new ones.

  11. The Excitatory Synaptic Transmission of the Nucleus of Solitary Tract Was Potentiated by Chronic Myocardial Infarction in Rats

    PubMed Central

    Feng, Ban; Zhang, Zi-Nan; Lei, Jie; Li, Yun-Qing; Du, Jian-Qing; Chen, Tao

    2015-01-01

    Angina pectoris is a common clinical symptom that often results from myocardial infarction. One typical characteristic of angina pectoris is that the pain does not match the severity of the myocardial ischemia. One possible explanation is that the intensity of cardiac nociceptive information could be dynamically regulated by certain brain areas. As an important nucleus for processing cardiac nociception, the nucleus of the solitary tract (NTS) has been studied to some extent. However, until now, the morphological and functional involvement of the NTS in chronic myocardial infarction (CMI) has remained unknown. In the present study, by exploring left anterior descending coronary artery ligation surgery, we found that the number of synaptophysin-immunoreactive puncta and Fos-immunoreactive neurons in the rat NTS two weeks after ligation surgery increased significantly. Excitatory pre- and postsynaptic transmission was potentiated. A bath application of a Ca2+ channel inhibitor GABApentin and Ca2+ permeable AMPA receptor antagonist NASPM could reverse the potentiated pre- and postsynaptic transmission, respectively. Meanwhile, rats with CMI showed significantly increased visceral pain behaviors. Microinjection of GABApentin or NASPM into the NTS decreased the CMI-induced visceral pain behaviors. In sum, our results suggest that the NTS is an important area for the process of cardiac afference in chronic myocardial infarction condition. PMID:25756354

  12. Ethanol injected into the hypothalamic arcuate nucleus induces behavioral stimulation in rats: an effect prevented by catalase inhibition and naltrexone.

    PubMed

    Pastor, Raúl; Aragon, Carlos M G

    2008-10-01

    It is suggested that some of the behavioral effects of ethanol, including its psychomotor properties, are mediated by beta-endorphin and opioid receptors. Ethanol-induced increases in the release of hypothalamic beta-endorphin depend on the catalasemic conversion of ethanol to acetaldehyde. Here, we evaluated the locomotor activity in rats microinjected with ethanol directly into the hypothalamic arcuate nucleus (ArcN), the main site of beta-endorphin synthesis in the brain and a region with high levels of catalase expression. Intra-ArcN ethanol-induced changes in motor activity were also investigated in rats pretreated with the opioid receptor antagonist, naltrexone (0-2 mg/kg) or the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg). We found that ethanol microinjections of 64 or 128, but not 256 microg, produced locomotor stimulation. Intra-ArcN ethanol (128 microg)-induced activation was prevented by naltrexone and AT, whereas these compounds did not affect spontaneous activity. The present results support earlier evidence indicating that the ArcN and the beta-endorphinic neurons of this nucleus are necessary for ethanol to induce stimulation. In addition, our data suggest that brain structures that, as the ArcN, are rich in catalase may support the formation of ethanol-derived pharmacologically relevant concentrations of acetaldehyde and, thus be of particular importance for the behavioral effects of ethanol.

  13. GABA-A and GABA-B receptors in the cuneate nucleus of the rat in vivo.

    PubMed

    Orviz, P; Cecchini, B G; Andrés-Trelles, F

    1986-09-01

    Electric stimulation of the rat forepaw evokes a negative potential (N-wave) at the ipsilateral cuneate nucleus. The responses of the N-wave to microiontophoretically applied GABA agonists and antagonists have been studied. Applications of GABA-A agonists (3-amino-propanesulfonic acid and muscimol) reduce the amplitude of the N-wave. This effect decreases during prolonged application, suggesting a desensitization of GABA-A receptors. In addition the effect of muscimol is reduced by (-)-bicuculline methiodide. Baclofen (a GABA-B agonist) also depresses the N-wave but its action lasts longer, is less reversible, shows no desensitization and is not blocked by (-)-bicuculline methiodide. The different responses of the N-wave to GABA-A and GABA-B agonists are compatible with the existence of different types of functional receptors for them in the cuneate nucleus of the rat. The receptors activated by muscimol (GABA-A) are clearly not the same as the ones activated by baclofen (conceivably GABA-B).

  14. Effect of local infusion of glutamate analogues into the nucleus accumbens of rats: an electrochemical and behavioural study.

    PubMed

    Svensson, L; Zhang, J; Johannessen, K; Engel, J A

    1994-04-18

    In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was used to investigate the effect of local infusion of glutamate analogues on dopamine (DA) release in rat nucleus accumbens. Infusion of a low dose of NMDA or AMPA (1 mM/0.2 microliter), but not L-glutamate or kainate, was followed a few minutes later by a large but short-lived increase in the extracellular concentration of DA. The involvement of spreading depression was indicated since this response could be repeated only after a short refractory period, and the response magnitude did not seem to be dependent on the dose infused. Furthermore, the increase in DA release was accompanied by a marked negative shift in brain field potential and a similar increase in release could be induced by local infusion of K+. The infusion of NMDA, AMPA or kainate was followed by behavioural activation of the animals but not convulsions. The behavioural response induced by NMDA was dose-dependently reduced by haloperidol, which suggests the involvement of a DA-dependent mechanism in this effect. Co-infusion of the DA transport inhibitors, nomifensine or GBR 12909, failed to alter the DA response to NMDA, while this response was completely blocked by co-infusion of tetrodotoxin or pretreatment with reserpine. It is evident from this study that local infusion of NMDA or AMPA may induce spreading depression in rat nucleus accumbens and that this condition is associated with a vast release of DA and behavioural activation.

  15. Single-prolonged stress induce changes of CaM/CaMKIIα in the rats of dorsal raphe nucleus.

    PubMed

    Xie, Huaju; Han, Fang; Shi, Xiuyu

    2012-05-01

    Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) is identified as a Ca2+-dependent kinase in brain involved in the activation of Tryptophan hydroxylase (TPH) acting through direct phosphorylation of TPH, and playing key roles in the signaling pathways initiated by various G protein-coupled 5-HT receptors. The goal of this study is to detect whether there are changes of CaM and CaMKIIα in dorsal raphe nucleus in the rats exposed to single-prolonged stress (SPS), which is a model employed in post-traumatic stress disorder (PTSD) study extensively. A total of 90 male Wistar rats were randomly divided into a normal control group and SPS groups of 7d, 14d. The changes of CaM/CaMKIIα were detected by immunohistochemistry, reverse transcription-polymerase chain reaction and western blot. Our results demonstrate that both expressions of CaM and CaMKIIα significantly increase (P < 0.001) in the SPS 7d group than that in the control group, and then decreased dramatically (P < 0.001) 14 days after SPS. Our results confirm that SPS induce changes of CaM/CaMKIIα in the dorsal raphe nucleus. Changes of CaM/CaMKIIα may be associated with the activation of 5-HT1A receptor, and may contribute to the progress of molecular mechanism of PTSD.

  16. Involvement of the dorsomedial hypothalamus and the nucleus tractus solitarii in chronic cardiovascular changes associated with anxiety in rats

    PubMed Central

    Sévoz-Couche, Caroline; Brouillard, Charly; Camus, Françoise; Laude, Dominique; De Boer, Sietse F; Becker, Chrystel; Benoliel, Jean-Jacques

    2013-01-01

    Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days. Five days later, the rats were found to be in an anxiety-like state. At this time point, we analysed HRV and BRS in the defeated rats, with or without treatment with the anxiolytic chlordiazepoxide (CDZ). HRV was reduced after social defeat, due to changes in the autonomic balance favouring the sympathetic over the parasympathetic component. Spontaneous and pharmacological baroreflex gains were also reduced. CDZ abolished anxiety-like symptoms as well as HRV and BRS alterations. Inhibition of the dorsomedial hypothalamus (DMH) with muscimol reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5-HT3 receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV. In conclusion, repeated social defeat in the rat lead to an anxiety-like state that was associated with lasting reduction in HRV and baroreflex gains. The DMH and the NTS were responsible for these chronic cardiovascular alterations. These regions may therefore constitute new therapeutic targets for reducing cardiac dysfunction and fibrillation in anxiety disorders. PMID:23297312

  17. Electroacupuncture Suppresses Discrete Cue-Evoked Heroin-Seeking and Fos Protein Expression in the Nucleus Accumbens Core in Rats

    PubMed Central

    Liu, Sheng; Zhu, Fenglei; Lai, Miaojun; Sun, Limin; Liu, Yijun; Zhou, Wenhua

    2012-01-01

    Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction. PMID:22454660

  18. GFAP expression in astrocytes of suprachiasmatic nucleus and medial preoptic area are differentially affected by malnutrition during rat brain development.

    PubMed

    Mendonça, João Esmeraldo Frota; Vilela, Maria Cristina Ramos; Bittencourt, Heitor; Lapa, Raíssa Maria; Oliveira, Francisco Gilberto; Alessio, Maria Luíza Martins; Guedes, Rubem Carlos Araújo; De Oliveira Costa, Miriam Stela Maris; Da Costa, Belmira Lara da Silveira Andrade

    2004-08-01

    The aim of the present study was investigate, in young rats, the effects of malnutrition on astrocyte distribution of two hypothalamic regions, the circadian pacemaker suprachiasmatic nucleus (SCN) and the medial preoptic area (MPA). Control rats were born from mothers fed on commercial diet since gestation and malnourished rats from mothers fed on multideficient diet, from the beginning of gestation (GLA group) or from the onset of lactation (LA group). After weaning, pups received ad libitum the same diet as their mothers, and were maintained under a 12/12 h light/dark cycle. The animals were analyzed either at 30-33, or 60-63 days of life. Brain coronal sections (50 microm) were processed to visualize glial fibrillary acidic protein (GFAP) immunoreactivity. Compared to control rats, both malnourished groups of 30 and 60 days exhibited a reduced number of GFAP-immunoreactive astrocytes in the SCN. The total GFAP-immunoreactive area in the SCN of the GLA group differed from the control group at both age ranges analyzed. The GFAP expression as measured by the relative optical density (ROD) exhibited a 50-60% reduction in the MPA in both malnourished groups, compared to controls. The results suggest that malnutrition early in life leads to alterations in gliogenesis or glial cell proliferation in both nuclei, being these alterations greater in the MPA. Compensatory plasticity mechanisms in the GFAP-expression seem to be developed in the astrocyte differentiation process in the SCN, especially when the malnutrition is installed from the lactation.

  19. Preliminary investigation of changes in the sexually dimorphic nucleus of the rat medial preoptic area following prenatal exposure to fenitrothion.

    PubMed

    Struve, Melanie F; Turner, Katie J; Dorman, David C

    2007-01-01

    In vitro, the organophosphate insecticide fenitrothion is a potent competitive androgen receptor antagonist, whereas in vivo it affects the development of the male rat reproductive system. The purpose of this pilot study was to determine whether prenatal exposure to fenitrothion affects development of the rat sexually dimorphic nucleus of the medial preoptic area (SDN-POA). Pregnant rats (n = 5-6 litters/group) were orally dosed with corn oil (vehicle) or fenitrothion (20 or 25 mg kg(-1) day(-1)) from gestation day (GD) 12-21. Offspring were euthanized after reaching sexual maturity (females 60-65 days old and males 96-105 days old) and the SDN-POA volumes determined for two rats/sex/litter. Tremors, increased lacrimation and decreased body weight gain were observed in dams from both fenitrothion exposure groups. Reproductive effects in male offspring, including reduced anogenital distance on postnatal day (PND) 1 and increased retention of areolae (PND 13) were observed following fenitrothion exposure at these dose levels. These effects did not persist into adulthood. There was a dose-related increase in the SDN-POA volume in males and a dose-related decrease in SDN-POA volume in females exposed to fenitrothion. These SDN-POA volume changes contrast with those seen with flutamide, another potent anti-androgen, and suggest that fenitrothion may have mixed endocrine effects on the developing brain.

  20. [Phosphorylation of protein kinase C in cerebrospinal fluid-contacting nucleus modulates the inflammatory pain in rats].

    PubMed

    Zhou, Fang; Wang, Jia-You; Tian, En-Qi; Zhang, Li-Cai

    2015-12-25

    The present study was aimed to investigate the role of cerebrospinal fluid-contacting nucleus (CSF-CN) neurons in modulation of inflammatory pain and underlying mechanism. The inflammatory pain model was made by subcutaneous injection of the complete Freund's adjuvant (CFA) into the left hind paw of rats. The phosphorylation level of PKC (p-PKC) was examined by Western blot. Thermal withdrawal latency (TWL) of the rats was measured to assess inflammatory pain. The results showed that, compared with the sham controls, the inflammatory pain model rats showed shortened TWL on day 1, 3, and 7 after CFA injection, as well as increased level of p-PKC in CSF-CN neurons at 24 h after CFA injection. The administration of GF109203X, a PKC inhibitor, into lateral ventricle decreased the level of p-PKC protein expression and increased TWL in the model rats. These results suggest that blocking the PKC pathway in CSF-CN neurons may be an effective way to reduce or eliminate the inflammatory pain.

  1. The monoamine stabilizer (-)-OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats.

    PubMed

    Feltmann, Kristin; Fredriksson, Ida; Wirf, Malin; Schilström, Björn; Steensland, Pia

    2016-03-01

    We recently established that the monoamine stabilizer (-)-OSU6162 (OSU6162) decreased voluntary alcohol-mediated behaviors, including alcohol intake and cue/priming-induced reinstatement, in long-term drinking rats, while blunting alcohol-induced dopamine output in the nucleus accumbens (NAc) of alcohol-naïve rats. Therefore, we hypothesized that OSU6162 attenuates alcohol-mediated behaviors by blunting alcohol's rewarding effects. Here, we evaluated the effects of long-term drinking and OSU6162 treatment (30 mg/kg, sc) on basal and alcohol-induced (2.5 g/kg, ip) NAc dopamine outputs in Wistar rats after 10 months of intermittent access to 20% alcohol. The results showed that basal and alcohol-induced NAc dopamine outputs were significantly lower in long-term drinking rats, compared with alcohol-naïve rats. In the long-term drinking rats, OSU6162 slowly increased and maintained the dopamine output significantly elevated compared with baseline for at least 4 hours. Furthermore, OSU6162 pre-treatment did not blunt the alcohol-induced output in the long-term drinking rats, a finding that contrasted with our previous results in alcohol-naïve rats. Finally, OSU6162 did not induce conditioned place preference (CPP) in either long-term drinking or alcohol-naïve rats, indicating that OSU6162 has no reinforcing properties. To verify that the CPP results were not due to memory acquisition impairment, we demonstrated that OSU6162 did not affect novel object recognition. In conclusion, these results indicate that OSU6162 attenuates alcohol-mediated behaviors by counteracting NAc dopamine deficits in long-term drinking rats and that OSU6162 is not rewarding on its own. Together with OSU6162's beneficial side-effect profile, the present study merits evaluation of OSU6162's clinical efficacy to attenuate alcohol use in alcohol-dependent patients. © 2015 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  2. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats

    PubMed Central

    Sun, Wenyan; Yan, Chunhong; Frost, Bess; Wang, Xin; Hou, Chen; Zeng, Mengqi; Gao, Hongli; Kang, Yuming; Liu, Jiankang

    2016-01-01

    High blood pressure, or “hypertension,” is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension. PMID:27713551

  3. Pain behavior changes following disc puncture relate to nucleus pulposus rather than to the disc injury per se: an experimental study in rats.

    PubMed

    Nilsson, Elin; Nakamae, Toshio; Olmarker, Kjell

    2011-03-16

    It has previously been demonstrated that disc puncture in the rat induced changes in grooming and wet dog shakes, two behavioral changes that may be linked to discomfort and neuropathic pain. In this study the aim was to separate the effects of disc injury and the epidural presence of nucleus pulposus. Following anesthesia, the L4-5 disc was exposed using a dorsal approach. Ten rats received a superficial disc injury without nucleus pulposus leakage and ten rats received nucleus pulposus from a donor rat without disc injury. In ten animals the L4-5 disc was punctured using a ventral approach, with 10 corresponding controls. Spontaneous behavior was assessed after surgery. The data was matched to historical control of dorsal sham surgery and disc puncture. The study showed that the effects of nucleus pulposus were more pronounced than the effects induced by the disc injury. Ventral disc puncture did not induce any behavioral changes different from sham exposure. In conclusion, the data from the study indicate that behavioral changes induced by disc puncture are more likely to relate to the epidural presence of nucleus pulposus than the disc injury per se.

  4. Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats.

    PubMed

    Haider, Arshad; Woodward, Nicholas C; Lominac, Kevin D; Sacramento, Arianne D; Klugmann, Matthias; Bell, Richard L; Szumlinski, Karen K

    2015-09-01

    In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0-30% v/v) under continuous-access procedures. The generalization of AAV effects to non-drug, palatable, sweet solutions was also determined in tests of sucrose (0-5% w/v) and saccharin (0-0.125% w/v) intake/preference. No net-flux in vivo microdialysis was conducted for glutamate in the NAc to relate Homer2-dependent changes in alcohol intake to extracellular levels of glutamate. Line differences were noted for sweet solution preference and intake, but these variables were not affected by intra-NAc AAV infusion in either line. In contrast, Homer2b over-expression elevated, while Homer2b knock-down reduced, alcohol intake in both lines, and this effect was greatest at the highest concentration. Strikingly, in P rats there was a direct association between changes in Homer2b expression and NAc extracellular glutamate levels, but this effect was not seen in Wistar rats. These data indicate that NAc Homer2b expression actively regulates alcohol consumption by rats, paralleling this previous observation in mice. Overall, these findings underscore the importance of mesocorticolimbic glutamate activity in alcohol abuse/dependence and suggest that Homer2b and/or its constituents may serve as molecular targets for the treatment of these disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Mu opioid receptor modulation in the nucleus accumbens lowers voluntary wheel running in rats bred for high running motivation.

    PubMed

    Ruegsegger, Gregory N; Toedebusch, Ryan G; Will, Matthew J; Booth, Frank W

    2015-10-01

    The exact role of opioid receptor signaling in mediating voluntary wheel running is unclear. To provide additional understanding, female rats selectively bred for motivation of low (LVR) versus high voluntary running (HVR) behaviors were used. Aims of this study were 1) to identify intrinsic differences in nucleus accumbens (NAc) mRNA expression of opioid-related transcripts and 2) to determine if nightly wheel running is differently influenced by bilateral NAc injections of either the mu-opioid receptor agonist D-Ala2, NMe-Phe4, Glyo5-enkephalin (DAMGO) (0.25, 2.5 μg/side), or its antagonist, naltrexone (5, 10, 20 μg/side). In Experiment 1, intrinsic expression of Oprm1 and Pdyn mRNAs were higher in HVR compared to LVR. Thus, the data imply that line differences in opioidergic mRNA in the NAc could partially contribute to differences in wheel running behavior. In Experiment 2, a significant decrease in running distance was present in HVR rats treated with 2.5 μg DAMGO, or with 10 μg and 20 μg naltrexone between hours 0-1 of the dark cycle. Neither DAMGO nor naltrexone had a significant effect on running distance in LVR rats. Taken together, the data suggest that the high nightly voluntary running distance expressed by HVR rats is mediated by increased endogenous mu-opioid receptor signaling in the NAc, that is disturbed by either agonism or antagonism. In summary, our findings on NAc opioidergic mRNA expression and mu-opioid receptor modulations suggest HVR rats, compared to LVR rats, express higher running levels mediated by an increase in motivation driven, in part, by elevated NAc opioidergic signaling.

  6. Reduced outward K+ conductances generate depolarizing after-potentials in rat supraoptic nucleus neurones.

    PubMed Central

    Li, Z; Hatton, G I

    1997-01-01

    1. Whole-cell patch clamp recordings were obtained from sixty-five rat supraoptic nucleus (SON) neurones in brain slices to investigate ionic mechanisms underlying depolarizing after-potentials (DAPs). When cells were voltage clamped around -58 mV, slow inward currents mediating DAPs (IDAP), evoked by three brief depolarizing pulses, had a peak of 17 +/- 1 pA (mean +/- S.E.M.) and lasted for 2.8 +/- 0.1 s. 2. No significant differences in the amplitude and duration were observed when one to three preceding depolarizing pulses were applied, although there was a tendency for twin pulses to evoke larger IDAP than a single pulse. The IDAP was absent when membrane potentials were more negative than -70 mV. In the range -70 to -50 mV, IDAP amplitudes and durations increased as the membrane became more depolarized, with an activation threshold of -65.7 +/- 0.7 mV. 3. IDAP with normal amplitude and duration could be evoked during the decay of a preceding IDAP. As frequencies of depolarizing pulses rose from 2 to 20 Hz, the times to peak IDAP amplitude were reduced but the amplitudes and durations did not change. 4. A consistent reduction in membrane conductance during the IDAP was observed in all SON neurones tested, and averaged 34.6 +/- 3.3%. Small hyperpolarizing pulses used to measure membrane conductances appeared not to disturb major ionic mechanisms underlying IDAP, since the slope and duration of IDAP with and without test pulses were similar. 5. The IDAP had an averaged reversal potential of -87.4 +/- 1.6 mV, which was close to the K+ equilibrium potential. An elevation in [K+]o reduced or abolished the IDAP, and shifted its reversal potential toward more positive levels. Perifusion of slices with 7.5-10 mM TEA, a K+ channel blocker, reversibly suppressed the IDAP. 6. Both Na+ and Ca2+ currents failed to induce an IDAP-like current during perifusion of slices with media containing high [K+]o or TEA. However, the IDAP was abolished by replacing external Ca2+ with

  7. Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus: potential mechanism of action in Parkinson's disease.

    PubMed

    Lee, Kendall H; Blaha, Charles D; Harris, Brent T; Cooper, Shannon; Hitti, Frederick L; Leiter, James C; Roberts, David W; Kim, Uhnoh

    2006-02-01

    The precise mechanism whereby continuous high-frequency electrical stimulation of the subthalamic nucleus ameliorates motor symptoms of Parkinson's disease is unknown. We examined the effects of high-frequency stimulation of regions dorsal to and within the subthalamic nucleus on dopamine efflux in the striatum of urethane-anaesthetized rats using constant potential amperometry. Complementary extracellular electrophysiological studies determined the activity of subthalamic nucleus neurons in response to similar electrical stimulation of the subthalamic nucleus. High-frequency stimulation of the subthalamic nucleus increased action potential firing in the subthalamic nucleus only during the initial stimulation period and was followed by a cessation of firing over the remainder of stimulation. Electrical stimulation of the subthalamic nucleus with 15 pulses elicited stimulus-time-locked increases in striatal dopamine efflux with maximal peak effects occurring at 50 Hz frequency and 300 microA intensity. Extended subthalamic nucleus stimulation (1000 pulses at 50 Hz; 300 microA) elicited a similar peak increase in striatal dopamine efflux that was followed by a relatively lower steady-state elevation in extracellular dopamine over the course of stimulation. In contrast, extended stimulation immediately adjacent and dorsal to the subthalamic nucleus resulted in an 11-fold greater increase in dopamine efflux that remained elevated over the course of the stimulation. Immunohistochemical staining for tyrosine hydroxylase revealed catecholaminergic fibers running immediately dorsal to and through the subthalamic nucleus. Taken together, these results suggest that enhanced dopamine release within the basal ganglia may be an important mechanism whereby high-frequency stimulation of the subthalamic nucleus improves motor symptoms of Parkinson's disease.

  8. Glutamate and Opioid Antagonists Modulate Dopamine Levels Evoked by Innately Attractive Male Chemosignals in the Nucleus Accumbens of Female Rats.

    PubMed

    Sánchez-Catalán, María-José; Orrico, Alejandro; Hipólito, Lucía; Zornoza, Teodoro; Polache, Ana; Lanuza, Enrique; Martínez-García, Fernando; Granero, Luis; Agustín-Pavón, Carmen

    2017-01-01

    Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction toward sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist β-funaltrexamine into the posterior ventral tegmental area does not affect preference for male chemosignals. Nevertheless, exposure to male-soiled bedding elicits an increase in dopamine efflux in the nucleus accumbens shell and core, measured by microdialysis. Infusion of the opioid antagonist naltrexone in the accumbens core does not significantly affect dopamine efflux during exposure to male chemosignals, although it enhances dopamine levels 40 min after withdrawal of the stimuli. By contrast, infusion of the glutamate antagonist kynurenic acid in the accumbens shell inhibits the release of dopamine and reduces the time that females spend investigating male-soiled bedding. These data are in agreement with previous reports in male rats showing that exposure to opposite-sex odors elicits dopamine release in the accumbens, and with data in female mice showing that the behavioral preference for male chemosignals is not affected by opioidergic antagonists. We hypothesize that glutamatergic projections from the amygdala into the accumbens might be important to modulate the neurochemical and behavioral responses elicited by sexual chemosignals in rats.

  9. Glutamate and Opioid Antagonists Modulate Dopamine Levels Evoked by Innately Attractive Male Chemosignals in the Nucleus Accumbens of Female Rats

    PubMed Central

    Sánchez-Catalán, María-José; Orrico, Alejandro; Hipólito, Lucía; Zornoza, Teodoro; Polache, Ana; Lanuza, Enrique; Martínez-García, Fernando; Granero, Luis; Agustín-Pavón, Carmen

    2017-01-01

    Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction toward sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist β-funaltrexamine into the posterior ventral tegmental area does not affect preference for male chemosignals. Nevertheless, exposure to male-soiled bedding elicits an increase in dopamine efflux in the nucleus accumbens shell and core, measured by microdialysis. Infusion of the opioid antagonist naltrexone in the accumbens core does not significantly affect dopamine efflux during exposure to male chemosignals, although it enhances dopamine levels 40 min after withdrawal of the stimuli. By contrast, infusion of the glutamate antagonist kynurenic acid in the accumbens shell inhibits the release of dopamine and reduces the time that females spend investigating male-soiled bedding. These data are in agreement with previous reports in male rats showing that exposure to opposite-sex odors elicits dopamine release in the accumbens, and with data in female mice showing that the behavioral preference for male chemosignals is not affected by opioidergic antagonists. We hypothesize that glutamatergic projections from the amygdala into the accumbens might be important to modulate the neurochemical and behavioral responses elicited by sexual chemosignals in rats. PMID:28280461

  10. The medial preoptic nucleus as a site of the thermogenic and metabolic actions of melanotan II in male rats.

    PubMed

    Monge-Roffarello, Boris; Labbe, Sebastien M; Lenglos, Christophe; Caron, Alexandre; Lanfray, Damien; Samson, Pierre; Richard, Denis

    2014-07-15

    The present study was designed to investigate the role of the medial preoptic nucleus (MPO) as a site of the thermogenic and metabolic effects of the α-melanocyte-stimulating hormone analog melanotan II (MTII). We also assessed the involvement of the dorsomedial hypothalamic nucleus (DMH) by investigating the effects of the MPO infusion of MTII in rats with DMH lesions produced by kainic acid. Infusion of MTII in the MPO led to increases in interscapular brown adipose tissue (iBAT) temperature and iBAT uptake of 14C-bromopalmitate. Both increases were blocked by DMH lesions. iBAT temperature increase (area under curve) and 14C-bromopalmitate uptake emerged as two correlated variables (r = 0.63, P < 0.001). DMH lesions also blocked MTII-induced expression of mRNAs coding for proteins involved in 1) thermogenesis [type II iodothyronine deiodinase (Dio2) and peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgc1α)], 2) lipolysis [hormone-sensitive lipase (Hsl)], and 3) lipogenesis [diacylglycerol-O-acyltransferase 2 (Dgat2), fatty acid synthase (Fas)], in iBAT of rats killed 1 h after MPO infusion of MTII. MTII also stimulated expression of genes in iWAT but only in rats with DMH lesions. These genes included glucose transporter member 4 (Glut4), glycerol-3-phosphate acyltransferase 3 (Gpat3), Dgat1, Dgat2, triglyceride lipase (Atgl), Hsl, and carnitine palmitoyltransferase 1β (Cpt1β). Altogether, the present results reveal the MPO as a site of the thermogenic and metabolic actions of MTII. They also contribute to establish the MPO-DMH duet as a significant target for melanocortins to modulate energy homeostasis.

  11. c-Fos expression after deep brain stimulation of the pedunculopontine tegmental nucleus in the rat 6-hydroxydopamine Parkinson model.

    PubMed

    Saryyeva, Assel; Nakamura, Makoto; Krauss, Joachim K; Schwabe, Kerstin

    2011-11-01

    Deep brain stimulation (DBS) is used to alleviate motor dysfunction in Parkinson's disease (PD). The pedunculopontine nucleus (PPN) may be a potential target for severe freezing and postural instability with 25 Hz stimulation being considered more effective than 130 Hz stimulation. Here we evaluated the expression of c-Fos after 25 Hz and 130 Hz DBS of the pedunculopontine tegmental nucleus (PPTg, i.e., the rodent equivalent to the human PPN) in the rat 6-hydroxydopamine (6-OHDA) PD model. Anaesthetized male Sprague Dawley rats with unilateral 6-OHDA-induced nigrostriatal lesions were stimulated with 25 Hz, 130 Hz, or 0 Hz sham-stimulation for 4h by electrodes implanted into the ipsilateral PPTg. Thereafter the distribution and number of neurons expressing the immediate early gene c-Fos, a marker for acute neuronal activity, was assessed. DBS of the PPTg induced strong ipsilateral c-Fos expression at the stimulation site, with 25 Hz having a more marked impact than 130 Hz. Additionally, c-Fos was strongly expressed in the central gray. In the dorsal part expression was stronger after 25 Hz stimulation, while in the medial and ventral part there was no difference between 25 Hz and 130 Hz stimulation. Expression in the basal ganglia was negligible. In the rat 6-OHDA PD model stimulation of the PPTg did not affect c-Fos expression in the basal ganglia, but had a strong impact on other functional circuitries. PPN stimulation in humans might therefore also have an impact on other systems than the motor system.

  12. Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep-wake regulation.

    PubMed

    Cui, Su-Ying; Li, Sheng-Jie; Cui, Xiang-Yu; Zhang, Xue-Qiong; Yu, Bin; Sheng, Zhao-Fu; Huang, Yuan-Li; Cao, Qing; Xu, Ya-Ping; Lin, Zhi-Ge; Yang, Guang; Song, Jin-Zhi; Ding, Hui; Wang, Zi-Jun; Zhang, Yong-He

    2016-02-01

    The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow-wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation. © 2015 International Society for Neurochemistry.

  13. Estrogen receptor {alpha} gene promoter 0/B usage in the rat sexually dimorphic nucleus of the preoptic area.

    PubMed

    Hamada, Tomohiro; Sakuma, Yasuo

    2010-04-01

    The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is two to four times larger in male rats than in females; however, the mechanism for the establishment of sexual dimorphism and the function of this nucleus is almost unknown. Perinatal estrogen can cause sexual dimorphism via the estrogen receptor alpha (ERalpha). Recently, transgenic rats were generated that express enhanced green fluorescent protein (EGFP) under the control of the ERalpha gene promoter 0/B to tag ERalpha-positive neurons in the brain. In the present study, we examined whether this EGFP expression could be a marker for the SDN-POA in adults. EGFP-labeled cells were distributed in the core of the SDN-POA (0/B-SDN) of male and female transgenic rats, in accordance with the Nissl staining and immunoreactivity for the SDN marker, calbindin. They were also immunoreactive for ERalpha. The core was bigger in volume and contained more 0/B-SDN neurons in males than in females. The EGFP-tagged cells were packed more densely in the female core than that in males. Subcutaneous injection of 100 mug 17beta-estradiol to females on the day of birth, or orchidectomy of male neonates, reversed the sexually dimorphic phenotype of the volume of the 0/B-SDN, despite not affecting the cell number. We suggest that this EGFP expression in the SDN-POA could be a useful marker to clarify the sexual differentiation and function of the SDN-POA. Moreover, the ERalpha gene promoter 0/B plays a key role in the organization of the sexual differentiation of the SDN-POA.

  14. Effects on serotonin of (-)nicotine and dimethylphenylpiperazinium in the dorsal raphe and nucleus accumbens of freely behaving rats.

    PubMed

    Ma, Z; Strecker, R E; McKenna, J T; Thakkar, M M; McCarley, R W; Tao, R

    2005-01-01

    The aim of this study was to investigate the neurochemical mechanism underlying the effect of nicotine and dimethylphenylpiperazinium (DMPP) on 5-hydroxytryptamine (5-HT) release in the dorsal raphe nucleus and nucleus accumbens of freely behaving rats. For comparison, lobeline, cytisine and RJR-2403 were also investigated. It was found that all drugs, when infused locally, evoked an increase of 5-HT in the dorsal raphe nucleus. However, the magnitudes of the 5-HT increase were comparatively different between the drugs in the ranking of their potency: DMPP>RJR 2403>nicotine>lobeline>cytisine. Both methyllycaconitine, a nicotinic acetylcholine receptor (nAChR) antagonist and methyllycaconitine, a selective alpha7-containing nAChR antagonist blocked the effects of nicotine and DMPP, suggesting that alpha7 subunit mediated the increases in 5-HT. However, DMPP was reported to increase 5-HT using non-nAChR mechanism [Lendvai B, Sershen H, Lajtha A, Santha E, Baranyi M, Vizi ES (1996) Differential mechanisms involved in the effect of nicotinic agonists DMPP and lobeline to release [3H]5-HT from rat hippocampal slices. Neuropharmacology 35:1769-1777]. To test if 5-HT carriers were involved, a selective 5-HT reuptake inhibitor citalopram (1 microM) was infused into the dorsal raphe nucleus before administration of nicotine or DMPP. As a result, citalopram significantly blocked the effect of DMPP, whereas it had no influence on nicotine. Finally, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was used to test whether the increases in 5-HT were depolarization-dependent. Administration of 8-OH-DPAT (0.1 mg/kg, s.c.) produced significant decreases in 5-HT in the animals treated with nicotine. In contrast, the effect of DMPP was not altered by 8-OH-DPAT, suggesting that the increases in 5-HT were independent of cell membrane depolarization. In conclusion, there are different mechanisms involved in nicotine- and DMPP-evoked increases in 5-HT. This

  15. Ultrastructure and immunocytochemical characteristics of cells in the octopus cell area of the rat cochlear nucleus: comparison with multipolar cells.

    PubMed

    Alibardi, Lorenzo

    2003-01-01

    Cells in the octopus cell area of the rat ventral cochlear nucleus have been connected to the monaural interpretation of spectral patterns of sound such as those derived from speech. This is possible by their fast onset of firing after each octopus cell and its dendrites have been contacted by many auditory fibres carrying different frequencies. The cytological characteristics that make these large cells able to perform such a function have been studied with ultrastructural immunocytochemistry for glycine, GABA and glutamate, and compared to that of other multipolar neurons of other regions of the ventral cochlear nucleus. Cells in the octopus cell area have an ultrastructure similar to large-giant D-multipolar neurons present in other areas of the cochlear nucleus, from which they differ by the presence of a larger excitatory axo-somatic synaptic input and larger mitochondria. Octopus cells are glycine and GABA negative, and glutamate positive with different degree. Large octopus cells receive more axo-somatic boutons than smaller octopus cells. Fusiform octopus cells are found sparsely within the intermediate acoustic striae. These cells are large to giant excitatory neurons (23-35 microm) with 62-85% of their irregular perimeter covered with large axo-somatic synaptic boutons. Most boutons contain round vesicles and are glycine and GABA negative but glutamate positive. The latter excitatory boutons represent about 70% of the input to octopus cells. Glycine positive boutons with flat and pleomorphic vesicles account for 9-10% of the input while GABA-ergic boutons with pleomorphic vesicles represent about 20% of the synaptic input. Other few, multipolar cells within the rat octopus cell area are surrounded by more inhibitory than excitatory terminals which contain flat and pleomorphic vesicles, a feature distinctive from that of true octopus cells. The latter resemble multipolar cells seen outside the octopus cell area that project to the contralateral inferior

  16. Nucleus-nucleus potentials

    SciTech Connect

    Satchler, G.R.

    1983-01-01

    The significance of a nucleus-nucleus potential is discussed. Information about such potentials obtained from scattering experiments is reviewed, including recent examples of so-called rainbow scattering that probe the potential at smaller distances. The evidence for interactions involving the nuclear spins is summarized, and their possible origin in couplings to non-elastic channels. Various models of the potentials are discussed.

  17. Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat.

    PubMed

    Horn, Charles C; De Jonghe, Bart C; Matyas, Kathleen; Norgren, Ralph

    2009-11-01

    Anticancer agents, such as cisplatin, stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice do not possess a vomiting response, and, therefore, in these species, the ingestion of kaolin clay (a pica response) has been used as an index of malaise. In the rat, cisplatin-induced kaolin intake is inhibited by antiemetic treatments. In addition, cisplatin activates vagal afferent fibers in the gut, and kaolin intake induced by cisplatin is largely dependent on an intact vagus. Nevertheless, little is known about the brain pathways controlling pica. We investigated the role of the lateral parabrachial nucleus (lPBN), a major visceral afferent link between the hindbrain and forebrain, in cisplatin-induced c-Fos expression and pica. Injection of cisplatin (6 mg/kg ip) produced c-Fos expression in the ventrolateral (external) lPBN, a region receiving viscerosensory input. In rats with bilateral ibotenic acid lPBN lesions, cisplatin treatment substantially increased kaolin intake compared with controls ( approximately 30 g vs. approximately 5 g, respectively, over 24 h). Food intake was reduced by cisplatin treatment and by apomorphine, an emetic agent that acts centrally. Unlike cisplatin, however, apomorphine stimulated kaolin intake to a similar degree in both the lesioned and control rats, suggesting that lPBN damage neither produces nonspecific effects nor enhances malaise in general. These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats.

  18. Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat

    PubMed Central

    De Jonghe, Bart C.; Matyas, Kathleen; Norgren, Ralph

    2009-01-01

    Anticancer agents, such as cisplatin, stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice do not possess a vomiting response, and, therefore, in these species, the ingestion of kaolin clay (a pica response) has been used as an index of malaise. In the rat, cisplatin-induced kaolin intake is inhibited by antiemetic treatments. In addition, cisplatin activates vagal afferent fibers in the gut, and kaolin intake induced by cisplatin is largely dependent on an intact vagus. Nevertheless, little is known about the brain pathways controlling pica. We investigated the role of the lateral parabrachial nucleus (lPBN), a major visceral afferent link between the hindbrain and forebrain, in cisplatin-induced c-Fos expression and pica. Injection of cisplatin (6 mg/kg ip) produced c-Fos expression in the ventrolateral (external) lPBN, a region receiving viscerosensory input. In rats with bilateral ibotenic acid lPBN lesions, cisplatin treatment substantially increased kaolin intake compared with controls (∼30 g vs. ∼5 g, respectively, over 24 h). Food intake was reduced by cisplatin treatment and by apomorphine, an emetic agent that acts centrally. Unlike cisplatin, however, apomorphine stimulated kaolin intake to a similar degree in both the lesioned and control rats, suggesting that lPBN damage neither produces nonspecific effects nor enhances malaise in general. These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats. PMID:19710391

  19. Neurokinin 3 Receptor-Expressing Neurons in the Median Preoptic Nucleus Modulate Heat-Dissipation Effectors in the Female Rat

    PubMed Central

    Mittelman-Smith, Melinda A.; Krajewski-Hall, Sally J.; McMullen, Nathaniel T.

    2015-01-01

    KNDy neurons facilitate tail skin vasodilation and modulate the effects of estradiol on thermoregulation. We hypothesize that KNDy neurons influence cutaneous vasodilation via projections to neurons in the median preoptic nucleus (MnPO) that express the neurokinin 3 receptor (NK3R). In support of this hypothesis, focal microinjections of senktide, an NK3R agonist, into the MnPO lowers core temperature (TCORE) in the female rat. To further study the role of MnPO NK3R neurons in thermoregulation, these neurons were specifically ablated using a conjugate of a selective NK3R agonist and saporin (NK3-SAP). NK3-SAP or blank-SAP (control) was injected into the MnPO/medial septum. Tail skin temperature (TSKIN) and TCORE were measured in ovariectomized rats exposed to 3 ambient temperatures (TAMBIENT) before and after estradiol-17β (E2) treatment. Before killing, we injected senktide (sc), monitored TCORE for 70 minutes, and harvested brains for Fos immunohistochemistry. Ablation of MnPO NK3R neurons lowered TSKIN at neutral and subneutral TAMBIENT regardless of E2 treatment. However, ablation did not prevent the effects of E2 on TCORE and TSKIN. In control rats, senktide injections induced hypothermia with numerous Fos-immunoreactive cells in the MnPO. In contrast, in NK3-SAP rats, senktide did not alter TCORE and minimal Fos-immunoreactive neurons were identified in the MnPO. These data show that NK3R neurons in the MnPO are required for the hypothermic effects of senktide but not for the E2 modulation of thermoregulation. The lower TSKIN in NK3-SAP–injected rats suggests that MnPO NK3R neurons, like KNDy neurons, facilitate cutaneous vasodilation, an important heat-dissipation effector. PMID:25825817

  20. Sex differences in alcohol consumption and alterations in nucleus accumbens endocannabinoid mRNA in alcohol-dependent rats.

    PubMed

    Henricks, Angela M; Berger, Anthony L; Lugo, Janelle M; Baxter-Potter, Lydia N; Bieniasz, Kennedy V; Craft, Rebecca M; McLaughlin, Ryan J

    2016-10-29

    Chronic intermittent alcohol (CIA) exposure produces altered motivational states characterized by anxiety and escalated alcohol consumption during withdrawal. The endocannabinoid (ECB) system contributes to these symptoms, and sex differences in alcohol dependence, as well as bidirectional interactions between ECBs and gonadal hormones have been documented. Thus, we evaluated sex differences in alcohol consumption, anxiety-like behavior, and ECB mRNA expression in the nucleus accumbens (NAc) of alcohol-dependent rats during acute withdrawal. Male rats exposed to six weeks of CIA showed escalated alcohol consumption during acute withdrawal and reductions in NAc N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), DAG lipase alpha (DAGLα), and monoacylglycerol lipase (MAGL) mRNA. Intact alcohol-dependent female rats also escalated their consumption, but notably, this effect was also present in non-dependent females. No differences in NAc ECB mRNA were observed between CIA- and air-exposed females during acute withdrawal. However, when these data were analyzed according to estrous stage, significant differences in NAPEPLD and MAGL mRNA expression emerged in the NAc of air-exposed control rats, which were absent in alcohol-dependent females. We subsequently measured alcohol consumption and NAc ECB mRNA in ovariectomized (OVX) females with or without estradiol (E2) replacement during withdrawal. Neither E2 nor CIA altered alcohol consumption in OVX females. However, E2 reduced both DAGLα and MAGL mRNA, suggesting that E2 may influence the biosynthesis and degradation of 2-arachidonoylglycerol (2-AG) in the NAc. Collectively, these studies indicate sexual dimorphism in alcohol consumption in non-dependent rats and suggest that E2-mediated alterations in NAc ECB mRNA expression during withdrawal may be a mechanism by which sex differences in alcohol dependence emerge. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Enduring increases in anxiety-like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats

    PubMed Central

    Yorgason, Jordan T.; España, Rodrigo A.; Konstantopoulos, Joanne K.; Weiner, Jeffrey L.; Jones, Sara R.

    2013-01-01

    Social isolation (SI) rearing, a model of early life stress, results in profound behavioral alterations, including increased anxiety-like behavior, impaired sensorimotor gating and increased self-administration of addictive substances. These changes are accompanied by alterations in mesolimbic dopamine function, such as increased dopamine and metabolite tissue content, increased dopamine responses to cues and psychostimulants, and increased dopamine neuron burst firing. Using voltammetric techniques, we examined the effects of SI rearing on dopamine transporter activity, vesicular release and dopamine D2-type autoreceptor activity in the nucleus accumbens core. Long–Evans rats were housed in group (GH; 4/cage) or SI (1/cage) conditions from weaning into early adulthood [postnatal day (PD) 28–77]. After this initial housing period, rats were assessed on the elevated plus-maze for an anxiety-like phenotype, and then slice voltammetry experiments were performed. To study the enduring effects of SI rearing on anxiety-like behavior and dopamine terminal function, another cohort of similarly reared rats was isolated for an additional 4 months (until PD 174) and then tested. Our findings demonstrate that SI rearing results in lasting increases in anxiety-like behavior, dopamine release and dopamine transporter activity, but not D2 activity. Interestingly, GH-reared rats that were isolated as adults did not develop the anxiety-like behavior or dopamine changes seen in SI-reared rats. Together, our data suggest that early life stress results in an anxiety-like phenotype, with lasting increases in dopamine terminal function. PMID:23294165

  2. Enhanced Endocannabinoid-Mediated Modulation of Rostromedial Tegmental Nucleus Drive onto Dopamine Neurons in Sardinian Alcohol-Preferring Rats

    PubMed Central

    Sagheddu, Claudia; De Felice, Marta; Casti, Alberto; Madeddu, Camilla; Spiga, Saturnino; Muntoni, Anna Lisa; Mackie, Kenneth; Marsicano, Giovanni; Colombo, Giancarlo; Castelli, Maria Paola; Pistis, Marco

    2014-01-01

    The progressive predominance of rewarding effects of addictive drugs over their aversive properties likely contributes to the transition from drug use to drug dependence. By inhibiting the activity of DA neurons in the VTA, GABA projections from the rostromedial tegmental nucleus (RMTg) are well suited to shift the balance between drug-induced reward and aversion. Since cannabinoids suppress RMTg inputs to DA cells and CB1 receptors affect alcohol intake in rodents, we hypothesized that the endocannabinoid system, by modulating this pathway, might contribute to alcohol preference. Here we found that RMTg afferents onto VTA DA neurons express CB1 receptors and display a 2-arachidonoylglycerol (2-AG)-dependent form of short-term plasticity, that is, depolarization-induced suppression of inhibition (DSI). Next, we compared rodents with innate opposite alcohol preference, the Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. We found that DA cells from alcohol-naive sP rats displayed a decreased probability of GABA release and a larger DSI. This difference was due to the rate of 2-AG degradation. In vivo, we found a reduced RMTg-induced inhibition of putative DA neurons in sP rats that negatively correlated with an increased firing. Finally, alcohol failed to enhance RMTg spontaneous activity and to prolong RMTg-induced silencing of putative DA neurons in sP rats. Our results indicate functional modifications of RMTg projections to DA neurons that might impact the reward/aversion balance of alcohol attributes, which may contribute to the innate preference observed in sP rats and to their elevated alcohol intake. PMID:25232109

  3. Enhanced endocannabinoid-mediated modulation of rostromedial tegmental nucleus drive onto dopamine neurons in Sardinian alcohol-preferring rats.

    PubMed

    Melis, Miriam; Sagheddu, Claudia; De Felice, Marta; Casti, Alberto; Madeddu, Camilla; Spiga, Saturnino; Muntoni, Anna Lisa; Mackie, Kenneth; Marsicano, Giovanni; Colombo, Giancarlo; Castelli, Maria Paola; Pistis, Marco

    2014-09-17

    The progressive predominance of rewarding effects of addictive drugs over their aversive properties likely contributes to the transition from drug use to drug dependence. By inhibiting the activity of DA neurons in the VTA, GABA projections from the rostromedial tegmental nucleus (RMTg) are well suited to shift the balance between drug-induced reward and aversion. Since cannabinoids suppress RMTg inputs to DA cells and CB1 receptors affect alcohol intake in rodents, we hypothesized that the endocannabinoid system, by modulating this pathway, might contribute to alcohol preference. Here we found that RMTg afferents onto VTA DA neurons express CB1 receptors and display a 2-arachidonoylglycerol (2-AG)-dependent form of short-term plasticity, that is, depolarization-induced suppression of inhibition (DSI). Next, we compared rodents with innate opposite alcohol preference, the Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. We found that DA cells from alcohol-naive sP rats displayed a decreased probability of GABA release and a larger DSI. This difference was due to the rate of 2-AG degradation. In vivo, we found a reduced RMTg-induced inhibition of putative DA neurons in sP rats that negatively correlated with an increased firing. Finally, alcohol failed to enhance RMTg spontaneous activity and to prolong RMTg-induced silencing of putative DA neurons in sP rats. Our results indicate functional modifications of RMTg projections to DA neurons that might impact the reward/aversion balance of alcohol attributes, which may contribute to the innate preference observed in sP rats and to their elevated alcohol intake.

  4. Cocaine-induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese-enhanced MRI.

    PubMed

    Perrine, Shane A; Ghoddoussi, Farhad; Desai, Kirtan; Kohler, Robert J; Eapen, Ajay T; Lisieski, Michael J; Angoa-Perez, Mariana; Kuhn, Donald M; Bosse, Kelly E; Conti, Alana C; Bissig, David; Berkowitz, Bruce A

    2015-11-01

    A long-standing goal of substance abuse research has been to link drug-induced behavioral outcomes with the activity of specific brain regions to understand the neurobiology of addiction behaviors and to search for drug-able targets. Here, we tested the hypothesis that cocaine produces locomotor (behavioral) sensitization that correlates with increased calcium channel-mediated neuroactivity in brain regions linked with drug addiction, such as the nucleus accumbens (NAC), anterior striatum (AST) and hippocampus, as measured using manganese-enhanced MRI (MEMRI). Rats were treated with cocaine for 5 days, followed by a 2-day drug-free period. The following day, locomotor sensitization was quantified as a metric of cocaine-induced neuroplasticity in the presence of manganese. Immediately following behavioral testing, rats were examined for changes in calcium channel-mediated neuronal activity in the NAC, AST, hippocampus and temporalis muscle, which was associated with behavioral sensitization using MEMRI. Cocaine significantly increased locomotor activity and produced behavioral sensitization compared with saline treatment of control rats. A significant increase in MEMRI signal intensity was determined in the NAC, but not AST or hippocampus, of cocaine-treated rats compared with saline-treated control rats. Cocaine did not increase signal intensity in the temporalis muscle. Notably, in support of our hypothesis, behavior was significantly and positively correlated with MEMRI signal intensity in the NAC. As neuronal uptake of manganese is regulated by calcium channels, these results indicate that MEMRI is a powerful research tool to study neuronal activity in freely behaving animals and to guide new calcium channel-based therapies for the treatment of cocaine abuse and dependence.

  5. Increased litter size and suckling intensity inhibit KiSS-1 mRNA expression in rat arcuate nucleus

    PubMed Central

    Noroozi, Atefeh; Shirazi, Mohammad Reza Jafarzadeh; Zamiri, Mohammad Javad; Tamadon, Amin; Akhlaghi, Amir; Tanideh, Nader; Niazi, Ali; Moghadam, Ali

    2014-01-01

    Objective(s): The effect of litter size and suckling intensity on the expression of KiSS-1 mRNA in the arcuate nucleus (ARC) of rats were evaluated. Materials and Methods: Thirty two pregnant and four non-lactating ovariectomized (as control group) rats were used in this experiment. Lactating rats were allotted to eight equal groups. In three groups, litter size was adjusted to 5, 10, or 15 pups upon parturition and allowed to suckle their pups continuously by 8 days postpartum. In the other three groups, litter size was adjusted to five upon birth; the pups were separated from the dams for 6 hr on day 8 postpartum, after which the pups were allowed to suckle their dams for 2.5, 5, or 7.5 min prior to killing the dams. Two groups of lactating rats with either 10 or 15 pups were separated from their pups for 6 hr on day 8 postpartum, after which the pups were allowed to suckle their dams for 5 min before the dams were killed on day 8 postpartum. The ARC was removed and the expression of KiSS-1 mRNA was evaluated, using real-time PCR. Results: The expression of KiSS-1 mRNA in the ARC was decreased as the litter size and intensity of suckling stimulus were increased. The effect of suckling intensity on the expression of KiSS-1 mRNA was more pronounced than that of litter size. Conclusion: Increased litter size and suckling intensity decreased KiSS-1 mRNA expression in the ARC which may contribute to lactation anestrus in rat. PMID:25422754

  6. Sleep deprivation reduces the citalopram-induced inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis of the rat.

    PubMed

    Prévot, E; Maudhuit, C; Le Poul, E; Hamon, M; Adrien, J

    1996-12-01

    Sleep deprivation (SD) for one night induces mood improvement in depressed patients. However, relapse often occurs on the day after deprivation subsequently to a sleep episode. In light of the possible involvement of central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission in both depression and sleep mechanisms, we presently investigated, in the rat, the effects of SD and recovery sleep on the electrophysiological response of 5-HT neurons in the nucleus raphe dorsalis (NRD) to an acute challenge with the 5-HT reuptake blocker citalopram. In all rats, citalopram induced a dose-dependent inhibition of the firing of NRD neurons recorded under chloral hydrate anaesthesia. After SD, achieved by placing rats in a slowly rotating cylinder for 24 h, the inhibitory action of citalopram was significantly reduced (with a concomitant 53% increase in its ED50 value). After a recovery period of 4 h, a normal susceptibility of the firing to citalopram was restored. The decreased sensitivity of 5-HT neuronal firing to the inhibitory effect of citalopram after SD probably results in an enhancement of 5-HT neurotransmission. Such an adaptive phenomenon (similar to that reported after chronic antidepressant treatment), and its normalization after recovery sleep, parallel the mood improvement effect of SD and the subsequent relapse observed in depressed patients. These data suggest that the associated changes in 5-HT autocontrol of the firing of NRD serotoninergic neurons are relevant to the antidepressant action of SD.

  7. PGC-1α may associated with the anti-obesity effect of taurine on rats induced by arcuate nucleus lesion.

    PubMed

    Cao, Peng-juan; Jin, Yong-jun; Li, Ming-e; Zhou, Rong; Yang, Mei-zi

    2016-01-01

    To observe the effect of taurine treatment in rats with monosodium glutamate (MSG)-induced obesity. Rats with MSG-induced obesity were administered taurine for five weeks. The Lee's index, food intake, blood pressure, body temperature, body mass index (BMI), fat weight, and triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels were compared. The PGC-1α expression levels in white and brown adipose were measured using reverse transcription polymerase chain reaction and western blotting, and pathological changes in the arcuate nucleus and liver were examined. Compared with the model group, BMI, TG, and LDL in the high and low taurine dose groups were significantly lower, while HDL was higher. Body temperature in the taurine treatment groups was higher, and blood pressure was lower. The weight of brown fat in the taurine treatment groups was significantly higher than in the model group, while the white fat weight was significantly lower. Compared with the control group, the PGC-1α levels in white and brown adipose were higher in the taurine treatment groups and more significantly up-regulated in brown adipose. This study suggests that taurine prevents obesity in MSG-treated rats and may be closely associated with energy metabolism.

  8. Characterizing effects of subthalamic nucleus deep brain stimulation on methamphetamine-induced circling behavior in hemi-Parkinsonian rats.

    PubMed

    So, Rosa Q; McConnell, George C; August, Auriel T; Grill, Warren M

    2012-09-01

    The unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model is frequently used to study the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson's disease. However, systematic knowledge of the effects of DBS parameters on behavior in this animal model is lacking. The goal of this study was to characterize the effects of DBS on methamphetamine-induced circling in the unilateral 6-OHDA lesioned rat. DBS parameters tested include stimulation amplitude, stimulation frequency, methamphetamine dose, stimulation polarity, and anatomical location of the electrode. When an appropriate stimulation amplitude and dose of methamphetamine were applied, high-frequency stimulation (> 130 Hz), but not low frequency stimulation (< 10 Hz), reversed the bias in ipsilateral circling without inhibiting movement. This characteristic frequency tuning profile was only generated when at least one electrode used during bipolar stimulation was located within the STN. No difference was found between bipolar stimulation and monopolar stimulation when the most effective electrode contact was selected, indicating that monopolar stimulation could be used in future experiments. Methamphetamine-induced circling is a simple, reliable, and sensitive behavioral test and holds potential for high-throughput study of the effects of STN DBS in unilaterally lesioned rats.

  9. Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus

    SciTech Connect

    Koo, Hyun-Young; Miyashita, Michio; Simon Cho, B.H.; Nakamura, Manabu T.

    2009-12-11

    Diets high in fructose cause hypertriglyceridemia and insulin resistance in part due to simultaneous induction of gluconeogenic and lipogenic genes in liver. We investigated the mechanism underlying the unique pattern of gene induction by dietary fructose. Male Sprague-Dawley rats (n = 6 per group) were meal-fed (4 h/d) either 63% (w/w) glucose or 63% fructose diet. After two weeks, animals were killed at the end of the last meal. Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats. Nuclear FoxO1 was elevated 1.7 times in fructose group, but did not reach significance (P = 0.08). Unexpectedly, no difference was observed in nuclear ChREBP between two groups. However, ChREBP DNA binding was 3.9x higher in fructose-fed animals without an increase in xylulose-5-phospate, a proposed ChREBP activator. In conclusion, the gene induction by dietary fructose is likely to be mediated in part by simultaneously increased ChREBP activity, SREBP-1 and possibly FoxO1 protein in nucleus.

  10. Decreased approach behavior and nucleus accumbens immediate early gene expression in response to Parkinsonian ultrasonic vocalizations in rats

    PubMed Central

    Kelm-Nelson, Cynthia A.; Holt, Lauren R.; Blue, Katherine V.; Ciucci, Michelle R.; Johnson, Aaron M.

    2015-01-01

    Many individuals with Parkinson disease (PD) have difficulty producing normal speech and voice, resulting in problems with interpersonal communication and reduced quality of life. Translational animal models of communicative dysfunction have been developed to assess disease pathology. However, it is unknown whether acoustic feature changes associated with vocal production deficits in these animal models lead to compromised communication. In rodents, male ultrasonic vocalizations (USVs) have a well-established role in functional inter-sexual communication. To test whether acoustic deficits in USVs observed in a PINK1 knockout (KO) PD rat model compromise communication, we presented recordings of male PINK1 KO USVs and normal wild-type (WT) USVs to female rat listeners. We measured approached behavior and immediate early gene expression (c-Fos) in brain regions implicated in auditory processing and sexual motivation. Our results suggest that females show reduced approach in response to PINK1 KO USVs compared to WT. Moreover, females exposed to PINK1 KO USVs had lower c-Fos immunolabeling in the nucleus accumbens, a region implicated in sexual motivation. These results are the first to demonstrate that vocalization deficits in a rat PD model result in compromised communication. Thus, the PINK1 KO PD model may be valuable for assessing treatments aimed at restoring vocal communicative function. PMID:26313334

  11. The effect of continuous ELF-MFs on the level of 5-HIAA in the raphe nucleus of the rat.

    PubMed

    Shahbazi-Gahrouei, Daryoush; Shiri, Leila; Alaei, Hojjatollah; Naghdi, Naser

    2016-03-01

    The aim of this study was to investigate the effect of continuous extremely low frequency magnetic fields (ELF-MFs) with a frequency of 10 Hz and an intensity of 690-720 μT on the level of 5-hydroxyindolacetic acid (5-HIAA) in adult male Wistar rats. A total of 24 adult Wistar male rats were used, and after exposure with an ELF-MF for 15 successive days, all rats in each test were anesthetized with chloral hydrate. Then, they were placed in a stereotaxic frame for surgery and a microdialysis process. Dialysate samples were analyzed to measure the amount of 5-HIAA by high performance liquid chromatography (HPLC) using electrochemical detection. Results showed that ELF-MF exposure for 15 days, 1 h daily, was not effective in altering the level of 5-HIAA. However, ELF-MF exposure for 15 days, 3 h daily, decreased the level of the 5-HIAA in the raphe nucleus. It can be concluded that ELF-MFs affect the serotonergic system and may be used to treat nervous system diseases. This study is an initial step towards helping cure depression using ELF-MFs.

  12. 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.

  13. A functionally relevant and long-term model of deep brain stimulation of the rat subthalamic nucleus: advantages and considerations.

    PubMed

    Spieles-Engemann, A L; Collier, T J; Sortwell, C E

    2010-10-01

    In this review we outline some relevant considerations with regards to the rat model of deep brain stimulation of the subthalamic nucleus (STN DBS). In order to optimize the rat STN DBS model in terms of predictive validity for the clinical situation we propose that the STN stimulation experimental design parameters in rodents should incorporate the following features: (i) stimulation parameters that demonstrate functional alleviation of symptoms induced by nigrostriatal dopamine (DA) denervation; (ii) stimulation duration that is relatively long-term and continuous; (iii) stimulation that is initiated at a time when the denervation status of the nigrostriatal system is known to be partial and progressing; (iv) stimulation current spread that is minimized and optimized to closely approximate the clinical situation; (v) the appropriate control conditions are included; and (vi) implantation to the STN target is verified post-mortem. Further research that examines the effect of long-term STN DBS on the neurophysiology and neurochemistry of STN circuitry is warranted. The rat model of functionally relevant long-term STN DBS provides a most favorable preclinical experimental platform in which to conduct these studies.

  14. Immunoreactive vasoactive intestinal polypeptide and vasopressin cells after a protein malnutrition diet in the suprachiasmatic nucleus of the rat.

    PubMed

    Rojas-Castañeda, J; Vigueras-Villaseñor, R M; Rojas, P; Rojas, C; Cintra, L

    2008-07-01

    The aim of the present study was to evaluate the effects of prenatal and postnatal protein deprivation on the morphology and density of vasopressin (VP) and vasoactive intestinal polypeptide (VIP) immunoreactive neurons in the suprachiasmatic nucleus (SCN) of young rats. Female Wistar rats were fed either 6% (malnourished group) or 25% (control group) casein diet five weeks before conception, during gestation and lactation. After weaning, the pups were maintained on the same diet until sacrificed at 30 days of age. The major and minor axes, somatic area and the density of VP- and VIP-immunoreactive neurons were evaluated in the middle sections of the SCN. The present study shows that chronic protein malnutrition (ChPM) in VP neurons induces a significant decrease in number of cells (-31%,) and a significant increase in major and minor axes and somatic area (+12.2%, +21.1% and +15.0%, respectively). The VIP cells showed a significant decrease in cellular density (-41.5%) and a significant increase in minor axis (+13.5%) and somatic area (+10.1%). Our findings suggest that ChPM induces abnormalities in the density and morphology of the soma of VP and VIP neurons. These alterations may be a morphological substrate underlying circadian alterations previously observed in malnourished rats.

  15. Characterizing Effects of Subthalamic Nucleus Deep Brain Stimulation on Methamphetamine-Induced Circling Behavior in Hemiparkinsonian Rats

    PubMed Central

    So, Rosa Q.; McConnell, George C.; August, Auriel T.; Grill, Warren M.

    2013-01-01

    The unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model is frequently used to study the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson’s disease. However, systematic knowledge of the effects of DBS parameters on behavior in this animal model is lacking. The goal of this study was to characterize the effects of DBS on methamphetamine-induced circling in the unilateral 6-OHDA lesioned rat. DBS parameters tested include stimulation amplitude, stimulation frequency, methamphetamine dose, stimulation polarity, and anatomical location of the electrode. When an appropriate stimulation amplitude and dose of methamphetamine were applied, high frequency stimulation (> 130 Hz), but not low frequency stimulation (< 10 Hz), reversed the bias in ipsilateral circling without inhibiting movement. This characteristic frequency tuning profile was only generated when at least one electrode used during bipolar stimulation was located within the STN. No difference was found between bipolar stimulation and monopolar stimulation when the most effective electrode contact was selected, indicating that monopolar stimulation could be used in future experiments. Methamphetamine-induced circling is a simple, reliable, and sensitive behavioral test and holds potential for high-throughput study of the effects of STN DBS in unilaterally lesioned rats. PMID:22692937

  16. Ovarian Hormone Deprivation Reduces Oxytocin Expression in Paraventricular Nucleus Preautonomic Neurons and Correlates with Baroreflex Impairment in Rats

    PubMed Central

    De Melo, Vitor U.; Saldanha, Rayssa R. M.; Dos Santos, Carla R.; De Campos Cruz, Josiane; Lira, Vitor A.; Santana-Filho, Valter J.; Michelini, Lisete C.

    2016-01-01

    The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic) neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN). Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry) within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation. PMID:27790154

  17. Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during lactation in rats.

    PubMed

    Suzuki, Yoshihiro; Nakahara, Keiko; Maruyama, Keisuke; Okame, Rieko; Ensho, Takuya; Inoue, Yoshiyuki; Murakami, Noboru

    2014-04-01

    The contribution of hypothalamic appetite-regulating peptides to further hyperphagia accompanying the course of lactation in rats was investigated by using PCR array and real-time PCR. Furthermore, changes in the mRNA expression for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were analyzed at all stages of pregnancy and lactation, and also after weaning. Food intake was significantly higher during pregnancy, lactation, and after weaning than during non-lactation periods. During lactation, ARC expression of mRNAs for agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in comparison with non-lactation periods. The increase in AgRP mRNA expression during lactation was especially marked. The plasma level of leptin was significantly decreased during the course of lactation, whereas that of acyl-ghrelin was unchanged. In addition, food intake was negatively correlated with the plasma leptin level during lactation. This study has clarified synchronous changes in the expression of many appetite-regulating peptides in ARC of rats during lactation. Our results suggest that hyperphagia during lactation in rats is caused by decreases in POMC and CCK expression and increases in AgRP expression in ARC, the latter being most notable. Together with the decrease in the blood leptin level, such changes in mRNA expression may explain the further hyperphagia accompanying the course of lactation.

  18. Different systems in the posterior hypothalamic nucleus of rats control theta frequency and trigger movement.

    PubMed

    Woodnorth, Mary-Anne; McNaughton, Neil

    2005-08-30

    Reduced frequency of theta activity is thought to compromise hippocampal function and so behavioural inhibition. The anxiolytic benzodiazepine chlordiazepoxide (CDP) reduces theta frequency when injected into the medial supramammillary nucleus (mSuM), posterior hypothalamic nucleus (PH) and dorsomedial hypothalamic nucleus (DMH). These hypothalamic effects on theta could underlie at least some behavioural effects of benzodiazepines. We have previously shown that in a fixed interval 60-s schedule (FI60), CDP injected into mSuM reduced both theta frequency and behavioural inhibition. The present experiments test the effect of injections into PH and DMH on theta and hippocampal-sensitive behaviour (FI60 and open field ambulation). Systemic CDP (5mg/kg i.p.) released, but PH/CDP (20microg in 0.5microl vehicle) suppressed FI responding, though they both reduced FI theta frequency. In the open field, both CDP i.p. and PH/CDP reduced ambulation, but only the systemic injection reduced ambulation theta frequency. Taken together with previous research, these results support a role for PH in the control of voluntary behaviour. They imply that this function may be suppressed, independently of theta, by benzodiazepines. An anxiolytic effect of PH/CDP in FI60 may, therefore, have been masked by a concurrent action of CDP on the PH motor system. DMH/CDP did not affect behaviour or theta in either experiment, despite the fact that this nucleus is involved in benzodiazepine mediation of risk assessment and the flight response. This suggests that, like the control of theta frequency by the hypothalamus, the neural mechanisms underlying anxiety are distributed in complex networks.

  19. Intracellular Physiology of the Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Effects of Neuromodulators

    DTIC Science & Technology

    1992-01-10

    Research 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Mental Retardation Research Center 760 Westwood Plaza (NPI 58...identify by block number) Our primary aim has been to study the electrophysiology of suprachiasmatic nucleus (SCN) neurons , with a focus on the...that these transmitters mediate all, or nearly all, of the fast synaptic potentials in virtually all SCN neurons . Preliminary experiments, however

  20. Auditory temporal processing deficits in children with periventricular brain injury.

    PubMed

    Downie, Andrea L S; Jakobson, Lorna S; Frisk, Virginia; Ushycky, Irene

    2002-02-01

    The present study investigated whether auditory temporal processing deficits are related to the presence and/or the severity of periventricular brain injury and the reading difficulties experienced by extremely low birthweight (ELBW: birthweight <1000 g) children. Results indicate that ELBW children with mild or severe brain lesions obtained significantly lower scores on a test requiring auditory temporal order judgments than ELBW children without periventricular brain injury or children who were full-term. Structural equation modeling indicated that a model in which auditory temporal processing deficits predicted speech sound discrimination and phonological processing ability provided a better fit for the data than did a second model, which hypothesized that auditory temporal processing deficits are associated with poor reading abilities through a working memory deficit. These findings suggest that an impairment in auditory temporal processing may contribute to the reading difficulties experienced by ELBW children. Copyright 2002 Elsevier Science (USA).

  1. Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons

    PubMed Central

    Han, Jin-Eon; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon

    2017-01-01

    The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K+ and Ca2+ channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K+ currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K+ currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs+ (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca2+ channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions. PMID:28280415

  2. Inhibitory effects of acupuncture manipulation and focal electrical stimulation of the nucleus submedius on a viscerosomatic reflex in anesthetized rats.

    PubMed

    Sumiya, E; Kawakita, K

    1997-02-01

    To examine the participation of nucleus submedius (Sm) in the medial thalamus of pain inhibitory systems, we investigated the effects of acupuncture and focal electrical stimulation of the Sm and adjacent brain sites (0.3 ms, 50 Hz, 50-100 microA, 10 s) on the EMG activity of the external oblique muscle evoked by colorectal distension in urethane-anesthetized Wistar rats. The viscerosomatic reflex (VSR) activity was suppressed after the administration of morphine (1.0 mg/kg, i.v.) and the effect was reversed by naloxone (0.5 mg/kg, i.v.). Transection of the spinal cord at the Th2 level also eliminated the VSR. Acupuncture manipulation applied to the cheek (manual rotation at 1 Hz) suppressed the VSR, and this inhibition was eliminated by microinjections of lidocaine into the bilateral Sm nuclei (0.5 microliter of 1.0% solution). Electrical stimulation in the ventral part but not the dorsal part of the Sm suppressed the VSR. The inhibition of the VSR induced by electrical stimulation of the Sm was not reversed by the administration of naloxone (1.0 mg/kg, i.v.). Electrical stimulation of the adjacent medial thalamic nuclei (mediodorsal nucleus (MD) or centromedial nucleus (CM)) and ventrobasal complex (VB) of the thalamus had very little effect on the VSR. These results suggests that the Sm is not only involved in the relay of nociceptive information to the cortex, but may also be involved in a non-opioid mediated pain inhibitory system and may participate, at least in part, in the suppressive effects of intense acupuncture manipulation on VSR activity.

  3. Stereospecific transport of triiodothyronine from plasma to cytosol and from cytosol to nucleus in rat liver, kidney, brain, and heart.

    PubMed Central

    Oppenheimer, J H; Schwartz, H L

    1985-01-01

    We have investigated the transport of L- and D-triiodothyronine (T3) from plasma to cellular cytoplasm and from cytoplasm to nucleus by estimating the concentration of free hormone in these compartments in rat liver, kidney, brain, and heart. We assessed the distribution of T3 in various tissues and its metabolism by standard isotopic techniques and measured plasma and cytosolic tissue T3 by radioimmunoassay. In addition, we determined the fraction of radiosensitive T3 associated with the cytosol in individual tissues and estimated the cytosolic volume per gram of tissue. Equilibrium dialysis allowed us to determine the binding power of cytosols and plasma, and in vitro saturation techniques provided values for the affinity (ka) for L- and D-T3 of isolated nuclei in aqueous solution at 37 degrees C. We calculated the free cytosolic hormone from the product of cytosolic T3 and the binding power of cytosol for T3, and the free intranuclear T3 from the ka and previously determined ratio of occupied-to-unoccupied binding sites under steady state conditions in euthyroid animals. Our results showed that the free cytosolic/free plasma concentrations for L-T3 and D-T3, respectively, were: liver 2.8, 21.6; kidney 1.17, 63.3; heart 1.31, 1.58; brain 0.86, 0.24. The free nuclear/free cytosolic ratios for L-T3 and D-T3, respectively, were: liver 58.2, 3.70; kidney 55.9, 1.54; heart 80.6, 24.9; and brain 251, 108.6. Our findings suggest that stereospecific transport occurs both from plasma to cytosol and from cytosol to nucleus. The high gradients from cytosol to nucleus imply that there is an energy-dependent process and appear to account for the differences in the nuclear association constant determined in vivo and in vitro. PMID:3965501

  4. Burst-firing activity of presumed 5-HT neurones of the rat dorsal raphe nucleus: electrophysiological analysis by antidromic stimulation.

    PubMed

    Hajós, M; Sharp, T

    1996-11-18

    We recently reported raphe neurones which frequently fired spikes in short bursts. However, the action potentials were broad and the neurones fired in a slow and regular pattern, suggesting they were an unusual type of 5-hydroxytryptamine (5-HT) neurone. In the present study, we investigated whether these putative burst-firing 5-HT neurones project to the forebrain and whether all spikes fired in bursts propagate along the axon. In anaesthetised rats, electrical stimulation of the medial forebrain bundle evoked antidromic spikes in both burst-firing neurones and in single-spiking, classical 5-HT neurones recorded in the dorsal raphe nucleus. Although the antidromic spike latency of the single-spiking and burst-firing neurones showed a clear overlap, burst-firing neurones had a significantly shorter latency than single-spiking neurones. For both burst-firing neurones and classical 5-HT neurones, antidromic spikes made collisions with spontaneously occurring spikes. Furthermore, in all burst-firing neurones tested, first, second and third order spikes in a burst could be made to collide with antidromic spike. Interestingly, in a small number of burst-firing neurones, antidromic stimulation evoked spike doublets, similar to those recorded spontaneously. From these data we conclude that burst-firing neurones in the dorsal raphe nucleus project to the forebrain, and each spike generated by the burst propagates along the axon and could thereby release transmitter (5-HT).

  5. Central connectivity of the chorda tympani afferent terminals in the rat rostral nucleus of the solitary tract.

    PubMed

    Park, Sook Kyung; Lee, Dae Seop; Bae, Jin Young; Bae, Yong Chul

    2016-03-01

    The rostral nucleus of the solitary tract (rNST) receives gustatory input via chorda tympani (CT) afferents from the anterior two-thirds of the tongue and transmits it to higher brain regions. To help understand how the gustatory information is processed at the 1st relay nucleus of the brain stem, we investigated the central connectivity of the CT afferent terminals in the central subdivision of the rat rNST through retrograde labeling with horseradish peroxidase, immunogold staining for GABA, glycine, and glutamate, and quantitative ultrastructural analysis. Most CT afferents were small myelinated fibers (<5 µm(2) in cross-sectional area) and made simple synaptic arrangements with 1-2 postsynaptic dendrites. It suggests that the gustatory signal is relayed to a specific group of neurons with a small degree of synaptic divergence. The volume of the identified synaptic boutons was positively correlated with their mitochondrial volume and active zone area, and also with the number of their postsynaptic dendrites. One-fourth of the boutons received synapses from GABA-immunopositive presynaptic profiles, 27 % of which were also glycine-immunopositive. These results suggest that the gustatory information mediated by CT afferents to the rNST is processed in a simple and specific manner. They also suggest that the minority of CT afferents are presynaptically modulated by GABA- and/or glycine-mediated mechanism.

  6. Effects of nicotine, methamphetamine and cocaine on extracellular levels of acetylcholine in the interpeduncular nucleus of rats.

    PubMed

    Hussain, Rifat J; Taraschenko, Olga D; Glick, Stanley D

    2008-08-08

    There is increasing evidence that the cholinergic habenulo-interpeduncular pathway and the dopaminergic mesolimbic pathway may jointly mediate the reinforcing properties of addictive drugs. However, the effects of addictive drug on the functioning of the habenulo-interpeduncular pathway have not been well-characterized. Thus, several drugs of abuse (i.e., nicotine, cocaine, amphetamine) have been shown to alter the morphology of the habenulo-interpeduncular pathway, causing selective degeneration of the cholinergic neurons in this area. On the other hand, morphine was shown to alter the neurochemistry of the habenulo-interpeduncular pathway, inducing biphasic changes in acetylcholine release in the interpeduncular nucleus. In order to determine the effects of cocaine, amphetamine and nicotine on cholinergic neurotr