The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
David Wirtshafter - One of the best experts on this subject based on the ideXlab platform.
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injections of Muscimol into the paraventricular thalamic nucleus but not mediodorsal thalamic nuclei induce feeding in rats
Brain Research, 2013Co-Authors: Thomas R. Stratford, David WirtshafterAbstract:The paraventricular thalamic nucleus (PVT) is a component of the midline thalamic group that is interconnected with several brain regions known to play important roles in the control of food intake, including the lateral hypothalamus and nucleus accumbens shell, suggesting that the PVT itself may be involved in mediating feeding behavior. In the current study, we examined whether inhibition of cells in the PVT with the GABAA agonist Muscimol could alter food intake in non-deprived rats. To control for possible spread of the drug, we also observed food intake after injections of Muscimol into the overlying ventricle or laterally adjacent mediodorsal thalamic nuclei (MD). We found that Muscimol injections into the central PVT dose-dependently increased food intake. In contrast, intra-MD injections of Muscimol resulted in a potent dose-dependent suppression of food intake, while those into the overlying ventricle had no effect. These results support the proposal that the PVT is a component of the neural circuitry controlling feeding behavior.
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inactivation of the median raphe nucleus increases intake of sucrose solutions a microstructural analysis
Behavioral Neuroscience, 2011Co-Authors: David Wirtshafter, John D. Davis, Thomas R. StratfordAbstract:Previous studies have shown that microinjections of the GABA-A agonist Muscimol into the median raphe nucleus (MR) result in large increases in the intake of solid foods. In the current study, we used microstructural techniques to characterize the effects of intra-MR Muscimol injections on the consumption of either a 0.05 M or a 0.29 M sucrose solution. After injections of either saline or Muscimol, animals consumed more of the 0.29 M than the 0.05 M solution, an effect which resulted primarily from increases in the initial rate of consumption with no change in the rate at which licking decayed across the test session. In contrast, intra-MR Muscimol injections had little effect on the initial licking rate, but greatly increased meal duration, indicating that this treatment affected ingestion in a different way than did altering the sucrose concentration. Muscimol injections produced a significantly larger increase in the intake of the 0.29 M than of the 0.05 M solution. Intra-MR Muscimol injections did not alter the within burst rate of licking, suggesting that they did not affect the functioning of the licking pattern generator. In contrast, these injections did increase the number of licks contained within “clusters”, that is groups of licks separated from each other by intervals of more than 0.5 sec. These findings show that inactivation of the MR produces a powerful effect on the intake of liquid diets, and that the nature of this effect is different than that produced here by changes in sucrose concentration and from those reported after pharmacological manipulations of a number of other brain systems. We additionally discuss several theoretical issues arising in the interpretation of microstructural data
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opposite effects on the ingestion of ethanol and sucrose solutions after injections of Muscimol into the nucleus accumbens shell
Behavioural Brain Research, 2011Co-Authors: Thomas R. Stratford, David WirtshafterAbstract:Abstract Injection of the GABA A receptor agonist Muscimol into the nucleus accumbens shell (AcbSh) elicits robust feeding in satiated rats, but has no effect on water intake. The current study was designed to examine whether intra-AcbSh Muscimol injections influence the intake of ethanol solutions in rats trained to drink using a limited access paradigm. We confirmed that bilateral injections of Muscimol (100 ng) into the AcbSh produce large increases in the intake of sucrose solutions and of the chow maintenance diet but found in two independent experiments that these injections potently reduce the intake of a 10% ethanol solution. Furthermore, intra-AcbSh Muscimol significantly increased intake of an ethanol–sucrose mixture. These results demonstrate that activating GABA A receptors in the vicinity of the AcbSh can have opposite effects on the intake of different caloric substances and are consistent with the possibility that GABAergic circuits in the AcbSh may play a role in mediating voluntary ethanol intake.
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nonserotonergic control of nucleus accumbens dopamine metabolism by the median raphe nucleus
Pharmacology Biochemistry and Behavior, 1992Co-Authors: David Wirtshafter, Radmila TrifunovicAbstract:Abstract Injections of the GABA agonist Muscimol into the median raphe nucleus (MR) have been shown to result in an acceleration of dopamine metabolism within the nucleus accumbens. To examine whether serotonergic mechanisms play a role in this effect, Muscimol or its vehicle was injected into the MR of either control subjects or of rats that had received prior injections of the serotonin-depleting agent p -chlorophenylalanine (PCPA). Although PCPA treatments produced massive depletions of forebrain serotonin, they failed to alter the effect of Muscimol infusions on dopamine metabolism. This finding suggests that the effects of intra-MR injections of muscinol on accumbens dopamine turnover do not result entirely from an interaction between serotonergic and dopaminergic systems.
Thomas R. Stratford - One of the best experts on this subject based on the ideXlab platform.
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injections of Muscimol into the paraventricular thalamic nucleus but not mediodorsal thalamic nuclei induce feeding in rats
Brain Research, 2013Co-Authors: Thomas R. Stratford, David WirtshafterAbstract:The paraventricular thalamic nucleus (PVT) is a component of the midline thalamic group that is interconnected with several brain regions known to play important roles in the control of food intake, including the lateral hypothalamus and nucleus accumbens shell, suggesting that the PVT itself may be involved in mediating feeding behavior. In the current study, we examined whether inhibition of cells in the PVT with the GABAA agonist Muscimol could alter food intake in non-deprived rats. To control for possible spread of the drug, we also observed food intake after injections of Muscimol into the overlying ventricle or laterally adjacent mediodorsal thalamic nuclei (MD). We found that Muscimol injections into the central PVT dose-dependently increased food intake. In contrast, intra-MD injections of Muscimol resulted in a potent dose-dependent suppression of food intake, while those into the overlying ventricle had no effect. These results support the proposal that the PVT is a component of the neural circuitry controlling feeding behavior.
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inactivation of the median raphe nucleus increases intake of sucrose solutions a microstructural analysis
Behavioral Neuroscience, 2011Co-Authors: David Wirtshafter, John D. Davis, Thomas R. StratfordAbstract:Previous studies have shown that microinjections of the GABA-A agonist Muscimol into the median raphe nucleus (MR) result in large increases in the intake of solid foods. In the current study, we used microstructural techniques to characterize the effects of intra-MR Muscimol injections on the consumption of either a 0.05 M or a 0.29 M sucrose solution. After injections of either saline or Muscimol, animals consumed more of the 0.29 M than the 0.05 M solution, an effect which resulted primarily from increases in the initial rate of consumption with no change in the rate at which licking decayed across the test session. In contrast, intra-MR Muscimol injections had little effect on the initial licking rate, but greatly increased meal duration, indicating that this treatment affected ingestion in a different way than did altering the sucrose concentration. Muscimol injections produced a significantly larger increase in the intake of the 0.29 M than of the 0.05 M solution. Intra-MR Muscimol injections did not alter the within burst rate of licking, suggesting that they did not affect the functioning of the licking pattern generator. In contrast, these injections did increase the number of licks contained within “clusters”, that is groups of licks separated from each other by intervals of more than 0.5 sec. These findings show that inactivation of the MR produces a powerful effect on the intake of liquid diets, and that the nature of this effect is different than that produced here by changes in sucrose concentration and from those reported after pharmacological manipulations of a number of other brain systems. We additionally discuss several theoretical issues arising in the interpretation of microstructural data
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opposite effects on the ingestion of ethanol and sucrose solutions after injections of Muscimol into the nucleus accumbens shell
Behavioural Brain Research, 2011Co-Authors: Thomas R. Stratford, David WirtshafterAbstract:Abstract Injection of the GABA A receptor agonist Muscimol into the nucleus accumbens shell (AcbSh) elicits robust feeding in satiated rats, but has no effect on water intake. The current study was designed to examine whether intra-AcbSh Muscimol injections influence the intake of ethanol solutions in rats trained to drink using a limited access paradigm. We confirmed that bilateral injections of Muscimol (100 ng) into the AcbSh produce large increases in the intake of sucrose solutions and of the chow maintenance diet but found in two independent experiments that these injections potently reduce the intake of a 10% ethanol solution. Furthermore, intra-AcbSh Muscimol significantly increased intake of an ethanol–sucrose mixture. These results demonstrate that activating GABA A receptors in the vicinity of the AcbSh can have opposite effects on the intake of different caloric substances and are consistent with the possibility that GABAergic circuits in the AcbSh may play a role in mediating voluntary ethanol intake.
Nandor Ludvig - One of the best experts on this subject based on the ideXlab platform.
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autoradiographic evidence for the transmeningeal diffusion of Muscimol into the neocortex in rats
Brain Research, 2012Co-Authors: Nandor Ludvig, Robert C Switzer, Hai M Tang, Ruben KuznieckyAbstract:Abstract Electrophysiological and behavioral studies have demonstrated that Muscimol administered through the cranial meninges can prevent focal neocortical seizures. It was proposed that transmeningeal Muscimol delivery can be used for the treatment of intractable focal neocortical epilepsy. However, it has not been proved that Muscimol administered via the transmeningeal route can penetrate into the neocortex. The purpose of the present study was to solve this problem by using combined autoradiography–histology methods. Four rats were implanted with epidural cups over the parietal cortices. A 50 μL mixture of [ 3 H] Muscimol and unlabeled Muscimol with a final concentration of 1.0 mM was delivered through each cup on the dura mater. After a 1-hour exposure, the Muscimol solution was removed and replaced with formalin to trap the transmeningeally diffused molecules. Then the whole brain was fixed transcardially, sectioned, with the sections subjected to autoradiography and thionine counterstaining. Results showed that (1) [ 3 H] Muscimol diffused through the meninges into the cortical tissue underlying the epidural cup in all rats. (2) [ 3 H] Muscimol-related autoradiography grains were distributed in all six neocortical layers. (3) [ 3 H] Muscimol-related autoradiography grains were localized to the cortical area underneath the epidural delivery site and were absent in the cerebral cortical white matter and other brain structures. This study provided evidence that Muscimol can be delivered via the transmeningeal route into the neocortical tissue in a spatially controlled manner. The finding further supports the rationale of using transmeningeal Muscimol for the treatment of intractable focal neocortical epilepsy.
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periodic transmeningeal Muscimol maintains its antiepileptic efficacy over three weeks without inducing tolerance in rats
Neuroscience Letters, 2011Co-Authors: Hai M Tang, Ruben Kuzniecky, Orrin Devinsky, Jacqueline A French, Nandor LudvigAbstract:Periodic transmeningeal administration of Muscimol into the neocortical epileptogenic zone via a subdurally implanted device has been proposed for the treatment of intractable focal neocortical epilepsy. It is unknown whether such Muscimol applications induce tolerance. The purpose of this study was to determine whether daily transmeningeal (epidural) Muscimol applications into the rat parietal cortex induce tolerance to the antiepileptic effect of this drug. Rats were chronically implanted with an epidural cup and adjacent epidural EEG electrodes over the right parietal cortex. After recovery 1.0 mM Muscimol was delivered into the implanted cortical area through the cup while the animal behaved freely, once per day for 4 consecutive days in each week, with each delivery followed within 3 min by the delivery of a seizure-inducing concentration of acetylcholine (Ach) into the same area. The study lasted for 3 weeks. In each week, one day was used to test the epileptogenicity of the examined cortical site by replacing Muscimol with saline prior to Ach delivery. The duration of Ach-induced EEG seizures was measured in each experimental session to assess the antiepileptic efficacy of Muscimol, while the rat's behavior was also monitored. The daily epidural Muscimol pretreatments prevented Ach-induced EEG and behavioral seizures in all rats. This antiepileptic action did not diminish over time and was maintained throughout the 3-week test period. When Muscimol was replaced with saline, the subsequent Ach administrations induced EEG and behavioral seizures. These results suggest that periodic transmeningeal administrations of a relatively low concentration of Muscimol into the neocortex over three weeks do not induce tolerance to the localized antiepileptic effects of this drug.
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transmeningeal Muscimol can prevent focal eeg seizures in the rat neocortex without stopping multineuronal activity in the treated area
Brain Research, 2011Co-Authors: Nandor Ludvig, Hai M Tang, Ruben Kuzniecky, Shirn L Baptiste, Geza Medveczky, Orrin Devinsky, Sertac N Artan, Piotr Mirowski, Sindhu Darisi, Jacqueline A FrenchAbstract:Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered Muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity. Rats were chronically implanted with a modified epidural cup over the right frontal cortex, with microelectrodes positioned underneath the cup. In each postsurgical experimental day, either saline or 0.005-, 0.05-, 0.5- or 5.0-mM Muscimol was delivered through the cup, followed by a 20-min monitoring of the multineuronal activity and the subsequent delivery of Ach in the same way. Saline and Muscimol pretreatment in the concentration range of 0.005-0.05 mM did not prevent EEG seizures. In contrast, 0.5-mM Muscimol reduced the average EEG Seizure Duration Ratio value from 0.30±0.04 to 0. At this Muscimol concentration, the average baseline multineuronal firing rate of 10.9±4.4 spikes/s did not change significantly throughout the 20-min pretreatment. Muscimol at 5.0mM also prevented seizures, but decreased significantly the baseline multineuronal firing rate of 7.0±1.8 to 3.7±0.9 spikes/s in the last 10 min of pretreatment. These data indicate that transmeningeal Muscimol in a submillimolar concentration range can prevent focal neocortical seizures without stopping multineuronal activity in the treated area, and thus this treatment is unlikely to interrupt local physiological functions.
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localized transmeningeal Muscimol prevents neocortical seizures in rats and nonhuman primates therapeutic implications
Epilepsia, 2009Co-Authors: Nandor Ludvig, Hai M Tang, Shirn L Baptiste, Geza Medveczky, Hans Von Gizycki, Jean Charchaflieh, Orrin Devinsky, Ruben KuznieckyAbstract:Summary Purpose: To determine whether Muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)–induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity. Methods: Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or Muscimol (0.25–12.5 mm) was delivered locally as a “pretreatment,” followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and Muscimol (2.5 mm) exposures were measured. In a last group of four rats, Muscimol (0.8–2.5 mm) was delivered epidurally during the ongoing, Ach-induced EEG seizure. Results: In contrast to ACSF pretreatments, epidural Muscimol pretreatment in rats completely prevented the seizures at and above 2.5 mm. In the monkeys, subarachnoid Muscimol pretreatments at 2.5 mm completely prevented the focal-seizure–inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 mm epidural Muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, Muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1–3 min. Conclusions: The results of this study suggest that Muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy.
Ruben Kuzniecky - One of the best experts on this subject based on the ideXlab platform.
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autoradiographic evidence for the transmeningeal diffusion of Muscimol into the neocortex in rats
Brain Research, 2012Co-Authors: Nandor Ludvig, Robert C Switzer, Hai M Tang, Ruben KuznieckyAbstract:Abstract Electrophysiological and behavioral studies have demonstrated that Muscimol administered through the cranial meninges can prevent focal neocortical seizures. It was proposed that transmeningeal Muscimol delivery can be used for the treatment of intractable focal neocortical epilepsy. However, it has not been proved that Muscimol administered via the transmeningeal route can penetrate into the neocortex. The purpose of the present study was to solve this problem by using combined autoradiography–histology methods. Four rats were implanted with epidural cups over the parietal cortices. A 50 μL mixture of [ 3 H] Muscimol and unlabeled Muscimol with a final concentration of 1.0 mM was delivered through each cup on the dura mater. After a 1-hour exposure, the Muscimol solution was removed and replaced with formalin to trap the transmeningeally diffused molecules. Then the whole brain was fixed transcardially, sectioned, with the sections subjected to autoradiography and thionine counterstaining. Results showed that (1) [ 3 H] Muscimol diffused through the meninges into the cortical tissue underlying the epidural cup in all rats. (2) [ 3 H] Muscimol-related autoradiography grains were distributed in all six neocortical layers. (3) [ 3 H] Muscimol-related autoradiography grains were localized to the cortical area underneath the epidural delivery site and were absent in the cerebral cortical white matter and other brain structures. This study provided evidence that Muscimol can be delivered via the transmeningeal route into the neocortical tissue in a spatially controlled manner. The finding further supports the rationale of using transmeningeal Muscimol for the treatment of intractable focal neocortical epilepsy.
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periodic transmeningeal Muscimol maintains its antiepileptic efficacy over three weeks without inducing tolerance in rats
Neuroscience Letters, 2011Co-Authors: Hai M Tang, Ruben Kuzniecky, Orrin Devinsky, Jacqueline A French, Nandor LudvigAbstract:Periodic transmeningeal administration of Muscimol into the neocortical epileptogenic zone via a subdurally implanted device has been proposed for the treatment of intractable focal neocortical epilepsy. It is unknown whether such Muscimol applications induce tolerance. The purpose of this study was to determine whether daily transmeningeal (epidural) Muscimol applications into the rat parietal cortex induce tolerance to the antiepileptic effect of this drug. Rats were chronically implanted with an epidural cup and adjacent epidural EEG electrodes over the right parietal cortex. After recovery 1.0 mM Muscimol was delivered into the implanted cortical area through the cup while the animal behaved freely, once per day for 4 consecutive days in each week, with each delivery followed within 3 min by the delivery of a seizure-inducing concentration of acetylcholine (Ach) into the same area. The study lasted for 3 weeks. In each week, one day was used to test the epileptogenicity of the examined cortical site by replacing Muscimol with saline prior to Ach delivery. The duration of Ach-induced EEG seizures was measured in each experimental session to assess the antiepileptic efficacy of Muscimol, while the rat's behavior was also monitored. The daily epidural Muscimol pretreatments prevented Ach-induced EEG and behavioral seizures in all rats. This antiepileptic action did not diminish over time and was maintained throughout the 3-week test period. When Muscimol was replaced with saline, the subsequent Ach administrations induced EEG and behavioral seizures. These results suggest that periodic transmeningeal administrations of a relatively low concentration of Muscimol into the neocortex over three weeks do not induce tolerance to the localized antiepileptic effects of this drug.
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transmeningeal Muscimol can prevent focal eeg seizures in the rat neocortex without stopping multineuronal activity in the treated area
Brain Research, 2011Co-Authors: Nandor Ludvig, Hai M Tang, Ruben Kuzniecky, Shirn L Baptiste, Geza Medveczky, Orrin Devinsky, Sertac N Artan, Piotr Mirowski, Sindhu Darisi, Jacqueline A FrenchAbstract:Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered Muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity. Rats were chronically implanted with a modified epidural cup over the right frontal cortex, with microelectrodes positioned underneath the cup. In each postsurgical experimental day, either saline or 0.005-, 0.05-, 0.5- or 5.0-mM Muscimol was delivered through the cup, followed by a 20-min monitoring of the multineuronal activity and the subsequent delivery of Ach in the same way. Saline and Muscimol pretreatment in the concentration range of 0.005-0.05 mM did not prevent EEG seizures. In contrast, 0.5-mM Muscimol reduced the average EEG Seizure Duration Ratio value from 0.30±0.04 to 0. At this Muscimol concentration, the average baseline multineuronal firing rate of 10.9±4.4 spikes/s did not change significantly throughout the 20-min pretreatment. Muscimol at 5.0mM also prevented seizures, but decreased significantly the baseline multineuronal firing rate of 7.0±1.8 to 3.7±0.9 spikes/s in the last 10 min of pretreatment. These data indicate that transmeningeal Muscimol in a submillimolar concentration range can prevent focal neocortical seizures without stopping multineuronal activity in the treated area, and thus this treatment is unlikely to interrupt local physiological functions.
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localized transmeningeal Muscimol prevents neocortical seizures in rats and nonhuman primates therapeutic implications
Epilepsia, 2009Co-Authors: Nandor Ludvig, Hai M Tang, Shirn L Baptiste, Geza Medveczky, Hans Von Gizycki, Jean Charchaflieh, Orrin Devinsky, Ruben KuznieckyAbstract:Summary Purpose: To determine whether Muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)–induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity. Methods: Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or Muscimol (0.25–12.5 mm) was delivered locally as a “pretreatment,” followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and Muscimol (2.5 mm) exposures were measured. In a last group of four rats, Muscimol (0.8–2.5 mm) was delivered epidurally during the ongoing, Ach-induced EEG seizure. Results: In contrast to ACSF pretreatments, epidural Muscimol pretreatment in rats completely prevented the seizures at and above 2.5 mm. In the monkeys, subarachnoid Muscimol pretreatments at 2.5 mm completely prevented the focal-seizure–inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 mm epidural Muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, Muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1–3 min. Conclusions: The results of this study suggest that Muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy.
João Carlos Callera - One of the best experts on this subject based on the ideXlab platform.
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at1 receptor blockade in the lateral parabrachial nucleus reduces the effects of Muscimol on sodium intake
Brain Research, 2011Co-Authors: Camila Zambone C Da Silva, José Vanderlei Menani, João Carlos CalleraAbstract:Abstract The blockade of the lateral parabrachial nucleus (LPBN) with GABAA receptor agonist Muscimol induces robust hypertonic NaCl and water intake by rats. In the present study we investigated the effects of previous injections of losartan (AT1 angiotensin receptor antagonist) into the LPBN on 0.3 M NaCl and water intake induced by Muscimol injected bilaterally in the same area in fluid replete rats and in rats treated with the diuretic furosemide combined with a low dose of the angiotensin-converting enzyme inhibitor captopril injected subcutaneously. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Bilateral injections of Muscimol (0.5 nmol/0.2 μl, n = 8) into the LPBN in fluid replete rats induced 0.3 M NaCl intake (23.4 ± 4.1 vs. saline: 0.4 ± 0.4 ml/3 h) and water intake (9.3 ± 1.9 vs. saline: 0.7 ± 0.4 ml/3 h) and pre-treatment of the LPBN with losartan (50 μg/0.2 μl) reduced 0.3 M NaCl intake (3.3 ± 2.5 ml/3 h) and water intake (4.0 ± 2.9 ml/3 h) induced by Muscimol. In rats treated with furosemide + captopril, pre-treatment with losartan into the LPBN attenuated the increase of 0.3 M NaCl intake produced by Muscimol (12.8 ± 5.3, vs. saline + Muscimol: 36.7 ± 6.7 ml/3 h) without changing water intake. Therefore, the results suggest that deactivation of LPBN inhibitory mechanisms by Muscimol injections into the LPBN is facilitated by endogenous angiotensin II acting on AT1 receptors in the LPBN, which drives rats to ingest large amounts of hypertonic NaCl.
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Sodium intake by hyperosmotic rats treated with a GABAA receptor agonist into the lateral parabrachial nucleus
Brain research, 2007Co-Authors: Everton Heidi Kimura, Laurival A De Luca, José Vanderlei Menani, Debora S. A. Colombari, Lisandra Brandino De Oliveira, João Carlos CalleraAbstract:Abstract Inhibitory mechanisms in the lateral parabrachial nucleus (LPBN) and central GABAergic mechanisms are involved in the regulation of water and NaCl intake. Besides increasing fluid depletion-induced sodium intake, the activation of GABAA receptors with Muscimol into the LPBN also induces ingestion of 0.3 M NaCl in normonatremic, euhydrated rats. It has been suggested that inhibitory mechanisms activated by osmotic signals are blocked by GABAA receptor activation in the LPBN, thereby increasing hypertonic NaCl intake. Therefore, in the present study we investigated the effects of Muscimol injected into the LPBN on water and 0.3 M NaCl intake in hyperosmotic cell-dehydrated rats (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. In euhydrated rats, Muscimol (0.5 nmol/0.2 μl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (24.6 ± 7.9 vs. vehicle: 0.5 ± 0.3 ml/180 min) and water (6.3 ± 2.1 vs. vehicle: 0.5 ± 0.3 ml/180 min). One hour after intragastric 2 M NaCl load (2 ml), bilateral injections of Muscimol into the LPBN also induced 0.3 M NaCl intake (22.1 ± 5.2 vs. vehicle: 0.9 ± 0.8 ml/210 min) and water intake (16.5 ± 3.6 vs. vehicle: 7.8 ± 1.8 ml/210 min). The GABAA antagonist bicuculline (0.4 nmol/0.2 μl) into the LPBN reduced the effect of Muscimol on 0.3 M NaCl intake (7.1 ± 2.1 ml/210 min). Therefore, the activation of GABAA receptors in the LPBN induces ingestion of 0.3 M NaCl by hyperosmotic cell-dehydrated rats, suggesting that plasma levels of renin or osmolarity do not affect sodium intake after the blockade of LPBN inhibitory mechanisms with Muscimol.
