-
Advances in Biochemical... 1981
Review
Topics: Amino Acids; Animals; Cats; Ibotenic Acid; In Vitro Techniques; Muscimol; Neurons; Oxazoles; Structure-Activity Relationship
PubMed: 7004116
DOI: No ID Found -
Pharmacology, Biochemistry, and Behavior Aug 1992Progestogenic stimulation of both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) within the midbrain is critical for normal...
Progestogenic stimulation of both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) within the midbrain is critical for normal receptivity in female hamsters. However, few estrogen-induced progestin receptors have been found in the midbrain. In addition, recent evidence suggests that progestin's action in the VTA is mediated nongenomically at the membrane. The present experiment investigated the possible role of GABAA receptors in mediating the effects of progesterone in this brain region. Ovariectomized female hamsters were bilaterally implanted with chronic cannulae aimed toward the ventral mesencephalon. Five days after surgery, animals were injected with 10 micrograms estradiol benzoate SC. Forty hours later, the same animals were injected with either 25 or 100 micrograms progesterone and at hour 43.5, 50 ng muscimol was infused in 0.5 microliters. Control animals received 0.5 microliters vehicle, sterile saline, or no infusion. At hour 44, animals were tested for sexual receptivity by placing them in an observation arena with a sexually experienced male for 10 min, during which lordosis duration was recorded. The following week, the same regimen was given with the alternate dose of progesterone. Histology revealed that only those animals that were infused with muscimol into the VTA had total lordosis durations that were significantly longer than the controls. Implants that missed the ventral tegmental area were much less effective. These results indicate that GABA might play a facilitatory role in enhancing the efficacy of threshold doses of progesterone. Whether this interaction is due to a direct effect of progestins on the GABAA receptor complex awaits further study.
Topics: Animals; Cricetinae; Drug Synergism; Estradiol; Female; Injections; Mesocricetus; Muscimol; Ovariectomy; Posture; Progesterone; Sexual Behavior, Animal; Stereotaxic Techniques; Tegmentum Mesencephali
PubMed: 1513871
DOI: 10.1016/0091-3057(92)90044-g -
European Journal of Pharmacology Dec 1998Brain acetylcholine and gamma-aminobutyric acid (GABA) are both involved in the regulation of central cardiovascular control. Despite data from anatomical and... (Comparative Study)
Comparative Study
Brain acetylcholine and gamma-aminobutyric acid (GABA) are both involved in the regulation of central cardiovascular control. Despite data from anatomical and electrophysiological experiments characterizing the interaction between central GABAergic and cholinergic neurotransmission, the potential significance of this interaction in central cardiovascular regulation remains unknown. The purpose of this study was to determine whether activation of GABA(A) receptors by intracerebroventricular or intrahypothalamic administration of muscimol affects the cholinergic agonist-induced cardiovascular responses. All experiments were performed in conscious, Sprague-Dawley rats instrumented with a guide cannula for drug injection and iliac arterial catheters for direct measurement of mean arterial pressure and heart rate. Administration of a cholinergic agonist, carbachol, either intracerebroventricularly or into the dorsomedial hypothalamic nucleus, produced a significant increase in mean arterial pressure, whereas injection of carbachol into the posterior hypothalamic nucleus caused a slight elevation in blood pressure. Pretreatment with muscimol 10 min before administration of carbachol prevented the carbachol-evoked blood pressure changes. On the other hand, carbachol produced variable changes in heart rate, depending on the site of injection. In [3H]quinuclydinyl benzilate binding experiments, muscimol did not displace the muscarinic radioligand from its binding sites, suggesting that it does not exert any direct antagonistic activity at muscarinic receptors. These results suggest that the dorsomedial hypothalamic nucleus is a potential site of action for microinjected carbachol and that the GABAergic system has an inhibitory influence on cholinergic neurons involved in blood pressure regulation.
Topics: Animals; Blood Pressure; Carbachol; Cholinergic Agonists; Drug Interactions; Female; GABA Agonists; Heart Rate; Hypothalamus; Injections, Intraventricular; Muscimol; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Receptors, Muscarinic
PubMed: 9874168
DOI: 10.1016/s0014-2999(98)00754-7 -
Brain Research Jan 2013The paraventricular thalamic nucleus (PVT) is a component of the midline thalamic group that is interconnected with several brain regions known to play important roles...
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 GABA(A) 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.
Topics: Animals; Dose-Response Relationship, Drug; Eating; Feeding Behavior; GABA-A Receptor Agonists; Injections, Intraventricular; Male; Mediodorsal Thalamic Nucleus; Microinjections; Muscimol; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Satiation; Third Ventricle
PubMed: 23111346
DOI: 10.1016/j.brainres.2012.10.043 -
Neuropharmacology Jan 1979
Topics: Aminooxyacetic Acid; Animals; Brain; Injections, Intravenous; Injections, Intraventricular; Male; Muscimol; Oxazoles; Pargyline; Proadifen; Rats; Time Factors; Tissue Distribution
PubMed: 418955
DOI: 10.1016/0028-3908(79)90009-1 -
Life Sciences 1990In order to assess the possible role of GABA receptor function in the hypnotic property of benzodiazepines, we have examined the sleep EEG in rats given the GABA agonist...
In order to assess the possible role of GABA receptor function in the hypnotic property of benzodiazepines, we have examined the sleep EEG in rats given the GABA agonist muscimol, alone and in combination with flurazepam. Muscimol 0.05 and 0.1 mg/kg IP failed to alter sleep latency or total sleep time, and did not interact with the sleep-enhancing properties of flurazepam 20 mg/kg IP. These observations, in conjunction with a previous study of bicuculline, suggest that the hypnotic property of benzodiazepines may not be mediated by alteration of GABAergic activity.
Topics: Animals; Electroencephalography; Flurazepam; Male; Muscimol; Rats; Rats, Inbred Strains; Sleep
PubMed: 2250581
DOI: 10.1016/0024-3205(90)90354-t -
Psychopharmacology Feb 1997To evaluate the discriminative stimulus effects of a direct-acting GABAA agonist, seven rats were trained to discriminate 1 mg/kg IP muscimol from saline under a...
To evaluate the discriminative stimulus effects of a direct-acting GABAA agonist, seven rats were trained to discriminate 1 mg/kg IP muscimol from saline under a two-lever fixed ratio (FR) 20 schedule of food reinforcement. The direct GABAA agonist THIP (4,5,6,7-tetrahydro-isoxazolo [5, 4,c]-pyridin-3-ol) produced increases in muscimol lever responding and substituted for muscimol in all subjects. Unlike results with muscimol, the highest levels of muscimol lever responding following THIP administration were often produced at doses which also decreased rates of responding. The GABAB agonist baclofen and the indirect-acting GABAA agonists pentobarbital and midazolam produced substitution for muscimol in some subjects, but not in others. The non-competitive NMDA antagonist phencyclidine (PCP) produced mixed results in these rats, from partial to full substitution (both dose-dependently and exhibiting in lack of dose-dependence) in some animals and a complete failure to substitute in another. The selective GABAA antagonist bicuculline dose-dependently blocked the muscimol discriminative stimulus in a majority of subjects. This study is the first report of successful training of a drug discrimination in rats using muscimol. Evidence is provided from substitution and antagonism testing with THIP and bicuculline, respectively, that the muscimol discrimination was mediated by actions at the GABA binding site on the GABAA receptor-ionophore complex. Results, also suggest that drug stimulus control by muscimol is weak compared to that of other types of GABA agonists previously studied using drug discrimination procedures in rodents.
Topics: Animals; Behavior, Animal; Dose-Response Relationship, Drug; Male; Muscimol; Rats; Rats, Sprague-Dawley; Smell
PubMed: 9085403
DOI: No ID Found -
The Journal of Pharmacy and Pharmacology Jun 1979
Topics: Animals; Anti-Anxiety Agents; Benzodiazepines; Drug Synergism; Injections; Male; Motor Activity; Muscimol; Oxazoles; Rats; Substantia Nigra; Time Factors
PubMed: 39155
DOI: 10.1111/j.2042-7158.1979.tb13546.x -
Psychopharmacology 1990Three hundred and twenty mouse pups of both sexes of the CD-1 outbred strain received IP muscimol and were subsequently assessed for locomotor activity (single Varimex...
Three hundred and twenty mouse pups of both sexes of the CD-1 outbred strain received IP muscimol and were subsequently assessed for locomotor activity (single Varimex 30-min session) and for hot-plate responding. Muscimol doses were 0.05, 0.1, or 0.2 mg/kg at 8 and 14 days, and 0.1, 0.5, or 1.0 mg/kg at 21, 28, and 35 days. Activity data showed a shift from an immature pattern at 8 and 14 days to an adult-like pattern from day 21 onwards (high initial activity followed by a marked within-session decrement). Muscimol was ineffective on day 8, and depressed activity from day 14 onwards. At 28 days, however, the higher-dose male group showed a non-monotonic trend of activity; that is an initial depression followed by a marked rebound hyperactivity. With regard to hot-plate exposure, muscimol was ineffective at 8 days, while it produced maximal analgesic effects on day 14, followed by a progressive decrease in drug sensitivity. Around day 70, mice of the former 0.1 mg/kg and saline groups were re-tested for locomotor activity and pain reactivity without additional drug treatment. Activity was generally higher in males than in females, and two groups habituated significantly less than the others (females tested in the muscimol state at 8 days and males tested in the saline state at 35 days). Moreover, prior testing at the earliest ages and prior muscimol exposure had additive attenuating effects on pain reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Aging; Animals; Brain Chemistry; Female; Habituation, Psychophysiologic; Male; Mice; Motor Activity; Muscimol; Myocardium; Pain; Reaction Time; Sex Factors
PubMed: 2392506
DOI: 10.1007/BF02245742 -
Electrophoresis Sep 2014In this study, the CZE method for rapid quantitative and qualitative determination of ibotenic acid and muscimol in Amanita mushrooms naturally grown in Poland was...
In this study, the CZE method for rapid quantitative and qualitative determination of ibotenic acid and muscimol in Amanita mushrooms naturally grown in Poland was developed. The investigations included the species of A. muscaria, A. pantherina, and A. citrina, collected in southern region of Poland. The studied hallucinogenic compounds were effectively extracted with a mixture of methanol and 1 mM sodium phosphate buffer at pH 3 (1:1 v/v) using ultrasound-assisted procedure. The obtained extracts were separated and determined by CZE utilizing a 25 mM sodium phosphate running buffer adjusted to pH 3 with 5% content of acetonitrile v/v. The calibration curves for both analytes were linear in the range of 2.5-7000 μg/mL. The intraday and interday variations of quantitative data were 1.0 and 2.5% RSD, respectively. The recovery values of analyzed compounds were over 87%. The identities of ibotenic acid and muscimol were confirmed by UV spectra, migration time, and measurements after addition of external standard.
Topics: Amanita; Electrophoresis, Capillary; Hallucinogens; Ibotenic Acid; Limit of Detection; Linear Models; Muscimol; Reproducibility of Results
PubMed: 24981810
DOI: 10.1002/elps.201400104