Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Muscimol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1978

Muscimol binding in rat brain: association with synaptic GABA receptors.

[3H]Muscimol binding to crude synaptic membrane fractions of the rat central nervous is saturable with a high affinity dissociation constant of 2.2 nM. The regional distribution of this binding in rat brain and the effects of freezing, sodium and Triton X-100 are similar to those previously reported for [3H]GABA binding to the the synaptic GABA receptor site. Also, the substrate specificity of [3H]muscimol binding is identifical to that observed for the GABA receptor. Thus, [3H]muscimol is displaced, stereospecifically, only by those drugs and amino acids which are known to neurophysiologically interact with the synaptic GABA receptor but is unaffected by agents which activate or inhibit other neurotransmitter receptors. This suggests that the behavioral effects observed after the systemic administration of muscimol are probably the result of GABA receptor activation.

Aminobutyrates↗
PubMed1995

Neuroactive steroid modulation of [3H]muscimol binding to the GABAA receptor complex in rat cortex.

Epalons are a subclass of neuroactive steroids which are positive allosteric modulators of the GABAA receptor acting via a unique site on the receptor complex. Enhancement of [3H]muscimol binding to the GABA recognition site was observed to be either full (> 150%) or limited (110-135%) and specific for epalons. Both one and two component modulation was observed. Saturation studies performed in the presence of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-P) showed that 3 alpha, 5 alpha-P increased the density of high affinity [3H]muscimol sites and doubled the affinity of low affinity sites. 3 alpha,5 alpha-P had no effect on the affinity of the high affinity site or the density of the low affinity site. These data indicate that: (1) epalons are potent, stereoselective enhancers of [3H]muscimol binding; (2) epalons display varying levels of efficacy and some exhibit two-component enhancement; and (3) 3 alpha,5 alpha-P enhancement of [3H]muscimol binding results from both an increased density of high affinity sites and an increased affinity for low affinity sites.

Anesthetics↗
PubMed2000

A comparison of the effects of bilateral and unilateral infusions of muscimol into the basal forebrain on cued detection of visual targets in rats.

This study investigated the role of the basal forebrain cholinergic system (BFCS) in rats' performance of a visuospatial attention task. Muscimol was infused bilaterally and unilaterally into the BFCS to inhibit cholinergic projections to the cortex. Muscimol slowed responding without significantly affecting side-bias. Bilateral infusions increased accuracy for all targets, whereas unilateral infusions reduced accuracy for targets contralateral to the infusion and increased accuracy for targets ipsilateral to the infusion. After a low unilateral dose of muscimol, invalid cues impaired detection of contralateral targets and spared detection of ipsilateral targets. A high unilateral dose of muscimol impaired detection of contralateral targets independently of cueing. These results suggest that interhemispheric imbalance in cortical activity by pharmacological manipulation of the BFCS can impair the detection of lateralized visual stimuli.

Animals↗
PubMed1978

Autoradiographic localization of gamma-aminobutyric acid receptors in the rat central nervous system by using [3H]muscimol.

Muscimol, a structural analogue and potent agonist of gamma-aminobutyric acid (GABA), was used in its tritiated form for the autoradiographic localization of GABA receptors in the rat central nervous system. [(3)H]Muscimol ([(3)H]M) was incubated with brain slices or was injected intracortically or into intraocular brain transplants. As indicated by [(3)H]M binding and autoradiographic silver grains, GABA receptors display a laminar distribution over the cerebellar cortex, cerebral cortex, and hippocampus (in order of decreasing quantity); and a nonlaminar distribution in the caudate nucleus and substantia nigra. [(3)H]M binding was not affected by brief prior treatment of brain slices with (-)nipecotic acid or guvacine, two potent inhibitors of GABA uptake, indicating receptor binding specificity. Systemic administration of unlabeled muscimol interferred with binding of [(3)H]M binding subsequently administered in vitro, indicating that muscimol or a metabolite of it traverses the blood/brain barrier and binds to receptor sites, possibly in a manner competitive with [(3)H]M. [(3)H]M binding was greatest in the cerebellum. Quantitative analyses of the distribution of autoradiographic silver grains in the cerebellar cortex and dentate nucleus showed a general distribution of GABA receptors in the neuropil: molecular layer > granular layer > cerebellar nuclei > white matter. The highest binding of [(3)H]M occurred on the Purkinje cell somatic surface, in the basket axon formation surrounding the cell body and its axon initial segment, and somewhat less on basket and stellate cell somata. Neuroglial cells of the cortex have no [(3)H]M binding capacity; some glial cells in the cerebellar nuclei do. The role of glial cells in GABA uptake, metabolism, and GABA-receptor-mediated mechanisms remains to be clarified. The distribution of GABA receptors as indicated by [(3)H]M binding differs from the distribution of [(3)H]GABA uptake and GABA synthesizing and degradative sites.

Aminobutyrates↗
PubMed1994

Effects of 8-OH-DPAT, 5-CT and muscimol on behaviour maintained by a DRL20 schedule of reinforcement, following microinjection into the dorsal or median raphe nuclei.

Experiments were performed to investigate the effects of microinjections of the 5-HT(1A) agonist 8- hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the non-selective 5-HT(1) agonist 5-carboxamidotryptamine (5-CT) and the GABA(A) agonist muscimol into the midbrain raphe nuclei, on behaviour maintained by a differential reinforcement of low rate (DRL) 20 schedule of food reinforcement. Following acquisition of responding under the DRL20 schedule, in which responses were reinforced only if they occurred at least 20s after the previous response, two groups of rats were prepared with a stainless steel guide cannula aimed at either the dorsal raphe nucleus or the median raphe nucleus. Injections of 8-OH-DPAT and 5-CT into the median raphe dose-dependently increased responding and reduced the number of reinforcers earned, leading to a net reduction in response efficiency from 45% to approximately 27% (5µg 8-OH-DPAT) and 22% (375ng 5-CT). Both drugs appeared to shift the frequency distribution of inter-response times (IRTs) towards shorter IRTs, and lowered the mean IRT. These effects were not observed after dorsal raphe injections of either drug. This pattern of results, together with results obtained in other paradigms measuring response inhibition, suggests that suppression of the activity of median raphe 5-HT neurones induces deficits in the ability to withhold responding. Muscimol increased responding, decreased the number of reinforcers earned and reduced response efficiency after both dorsal raphe and median raphe injections. These effects were more pronounced following median raphe injections, and were of considerably greater magnitude than those observed following treatment with the 5-HT agonists. Muscimol injected into the median raphe lowered the mean IRT, and increased the frequency of short duration IRTs. Thus, stimulation of GABA(A) receptors within the median raphe induces a pattern of behavioural disruption in the DRL task, that is more severe than that resulting from selective inhibition of 5-HT neural activity. The effects of muscimol probably arise from a general behavioural activation, rather than a specific deficit in the ability to withhold responding.

Journal Article↗
PubMed1997

Development of MK-801, kainate, AMPA, and muscimol binding sites and the effect of dark rearing in rat visual cortex.

We used quantitative autoradiography to determine whether the development of glutamate receptors correlates with the plastic period for monocular deprivation in rat visual cortex. To study glutamate receptors, we incubated sections of rat visual cortex with tritiated (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10imin e maleate (MK-801), tritiated kainate, and tritiated amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA). [3H]MK-801 is a noncompetitive ligand for the N-methyl-D-aspartate (NMDA) receptor. [3H]kainate and [3H]AMPA are competitive ligands for non-NMDA receptors. To compare glutamate binding sites with a nonglutamate binding site, we studied [3H]muscimol, which binds to gamma-aminobutyric acid (GABA)A receptors. [3H]MK-801 binding was maximal at postnatal day 26 (P26) and decreased in adulthood. [3H]AMPA binding was maximal at P18. [3H]kainate binding and [3H]muscimol binding were not age dependent. Dark rearing partially prevented the age-dependent decrease in [3H]MK-801 binding but had no effect on [3H]kainate or [3H]AMPA binding. Dark rearing decreased muscimol binding in adult animals. These results suggest that NMDA receptors, but not other glutamate receptors or GABAA receptors, are likely to be critical for developmental plasticity in rat visual cortex.

Animals↗
PubMed2006

Ventral hippocampal muscimol disrupts context-specific fear memory retrieval after extinction in rats.

Research aimed at understanding Pavlovian fear memory extinction has yielded considerable insight into the conditions under which fear memories may become inhibited. After extinction, Pavlovian fear memory retrieval is context-specific. Fear memories are not expressed in the extinction context, but they are expressed in every other context. Research indicates that the dorsal hippocampus mediates the context-specific expression of fear memory, but the role of the ventral hippocampus in mediating this process is unknown. Insofar as the ventral hippocampus is involved in the acquisition and expression of both context and tone fear, we asked whether GABA systems in the ventral hippocampus mediate context-specific fear memory retrieval after extinction. Experiment 1 showed that ventral hippocampal inactivation with muscimol disrupted context-specific fear memory retrieval. Experiment 2 showed that rats infused with muscimol can discriminate a context in which they were shocked from a neutral context. Nonetheless, they do appear to have a mild impairment in this task. Experiment 3 showed that ventral hippocampal muscimol did not disrupt locomotor activity, but did result in a slight increase in freezing and grooming, an effect that cannot explain the context-specific retrieval deficit demonstrated in experiment 1. These data are consistent with a role for the ventral hippocampus in mediating context-specific fear memory retrieval.

Animals↗
PubMed1993

GABA agonist "muscimol" is neuroprotective in repetitive transient forebrain ischemia in gerbils.

The damaging effects from transient forebrain ischemia may be a result of excessive excitability or loss of inhibitory influences. In the brain, GABA acts as the major inhibitory neurotransmitter and its loss may be an important factor leading to delayed neuronal damage in the substantia nigra reticulata (SNr). In this study, we looked at the protective effects of muscimol, a GABA A agonist in a gerbil model of repetitive forebrain ischemia. For cerebral ischemia, we used three episodes of 2 min with a reperfusion period of 1 h between the insults. Histological evaluations were done 7 days after the insult using silver degeneration staining. Muscimol was infused into the third ventricle continuously for 7 days beginning just prior to the insult. There were a total of 20 animals, 12 treated with muscimol and the other 8 serving as controls. At 7 days, there was significant protection in the cortex (P = 0.007), hippocampus [CA1 (P = 0.01), CA4 (P = 0.015)], substantia nigra reticulata (P = 0.007), striatum (P = 0.049), and thalamus (P = 0.012). All statistical comparisons were done using nonparametric tests (Mann-Whitney U test). Our study shows that potentiation of inhibitory mechanisms may be important mechanisms of neuronal protection from the effects of repetitive ischemia and the effects are not limited to the SNr. Further studies are needed to better understand their mechanism of action.

Animals↗
PubMed1994

Transsynaptic effect of an intrastriatal fetal nigral graft on the sensitivity of the substantia nigra pars reticulata to muscimol in the rat.

In the present study, we have investigated the effect of a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway and of a fetal nigral graft in the striatum on circling induced by unilateral microinjection of muscimol in a target structure of the striatum, the substantia nigra pars reticulata. A group of ovariectomized female rats received a unilateral nigral lesion with 6-hydroxydopamine. The lesioned animals were then tested for apomorphine circling (0.25 mg/kg sc). The animals which displayed circling with this drug were divided into two groups with equivalent circling rate. One group received a graft of 1.5 x 10(6) cells taken from the ventral mesencephalon of 14- to 15-day-old rat embryos and the other was kept as control. Six months after the graft, all animals received one microinjection on each side of the GABAergic agonist muscimol (25 ng/0.5 microliters) in site A (rostral part) or in site B (caudal part) of the substantia nigra pars reticulata using indwelling guide cannulae. Circling was monitored during 90 min after the injection. Our results show that: (1) Unilateral degeneration of the nigrostriatal pathway was associated with a decrease of contralateral rotation when muscimol was injected in site A (rostral part) and an increase when administrated in site B (caudal part) of the substantia nigra pars reticulata on the lesioned side compared to the intact side. (2) A fetal nigral graft implanted into the striatum can normalize the changes in GABAergic sensitivity in site A but not in site B of the substantia nigra pars reticulata.

Animals↗
PubMed1997

Intraseptal infusions of muscimol impair spontaneous alternation performance: infusions of glucose into the hippocampus, but not the medial septum, reverse the deficit.

As observed with intraseptal injections of opioid receptor agonists, direct infusions of GABAergic receptor agonists into the medial septum impair performance on several tasks that involve spatial or working memory processes in rats. Because the effects of opioid-induced impairments can be reliably reversed by concomitant intraseptal infusions of glucose, the experiments reported here determined whether impairments produced by GABAergic agonists would similarly be reversed by glucose. The findings of Experiment 1 showed, in male Sprague-Dawley rats, that intraseptal infusions of the GABA agonist muscimol (1 or 3 nmol/0.5 microliter) impaired spontaneous alternation performance. The results of Experiment 2 indicated that intraseptal infusions of glucose (8, 17, or 33 nmol) or glutamate (15 or 30 nmol) did not attenuate the muscimol-induced deficit on spontaneous alternation performance, whereas infusions of the GABAergic antagonist bicuculline methiodide (0.1 nmol) did. However, the findings of Experiment 3 indicated that glucose injections (50 nmol/0.5 microliter) into the hippocampus did reverse the impairing effect of the intraseptal muscimol infusions. Combined, these findings suggest that the neurochemical regulation of learning and memory may involve hierarchical interactions between particular neurotransmitter and neuroanatomical systems. Specifically, medial septal GABAergic effects on spontaneous alternation prevail over those of glucose or glutamate in the medial septum, but are overridden by the effects of glucose in the hippocampus.

Animals↗
PubMed1999

Differential effects of post-training muscimol and AP5 infusions into different regions of the cingulate cortex on retention for inhibitory avoidance in rats.

Adult male Wistar rats were bilaterally implanted with indwelling cannulae in four different coordinates of the cingulate cortex: (1) the anterior cingulate (AC), (2) the rostral region of the posterior cingulate (RC), (3) the upper portion of the caudal region of the posterior cingulate (UC), and (4) the lower portion of the caudal region of the posterior cingulate (LC). After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock). Either immediately, or 90 or 180 min after training, animals received a 0.5-microl infusion of vehicle (phosphate buffer, pH 7.4), of muscimol (0.5 microg), or of AP5 (5.0 microg). Retention testing was carried out 24 h after training. Muscimol was amnestic when given into any of the three coordinates of the posterior cingulate cortex 90 min after training, and when given into LC immediately post-training. In addition, AP5 was amnestic when given into UC 90 min post-training, but not when given into any other region and/or at any other time. None of the treatments had any effect when given into AC. The results suggest that memory processing of the inhibitory avoidance task is regulated by the posterior but not by the anterior cingulate cortex, through muscimol-sensitive synapses, relatively late after training. AP5-sensitive synapses appear to play a very limited role in these processes, restricted to UC.

2-Amino-5-phosphonovalerate↗
PubMed1998

Potentiation of muscimol-induced long-term depression by benzodiazepines and prevention or reversal by pregnenolone sulfate.

We have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal slices. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone. It was also shown that glutamate receptor activity or extracellular calcium are not involved in the induction of this type of long-term depression. The present study investigated the possible relation between muscimol-induced long-term depression and barbiturates/benzodiazepine-induced amnesia and attempts to determine the possible effect of pregnenolone sulfate on muscimol-induced long-term depression. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that pentobarbital, benzodiazepines and pregnanolone at concentrations that did not have any effect themselves on the population spike, potentiate the ability of muscimol to induce long-term depression. In addition to this, the long-term depression was either blocked or reversed by pregnenolone sulfate at concentrations (10 microM) where pregnenolone sulfate did not induce any multiple burst or increase of spike size. The results suggest that the potentiation of this type of long-term depression by benzodiazepines and barbiturates can explain the main adverse effect of these drugs, amnesia and cognitive impairment. Moreover, the prevention or reversal of this type of long-term depression by pregnenolone sulfate, may suggest a clinical application of this agent in the management of amnesia or dementia.

Amnesia↗
PubMed2001

Changes of [3H]MK-801, [3H]muscimol and [3H]flunitrazepam binding in rat brain by the prolonged ventricular infusion of ginsenoside Rc and Rg1.

In the present study, we have investigated the effects of centrally administered ginsenoside Rc and Rg1 on the modulation of the NMDA receptor and GABA(A)receptor binding in rat brain. The NMDA receptor binding was analysed by quantitative autoradiography using [(3)H]MK-801 binding, and the GABA(A)receptor bindings were analysed by using [(3)H]muscimol and [(3)H]flunitrazepam binding in rat brain slices. Rats were infused with ginsenoside Rc or Rg1 (10 microg/10 microl h(-1), i.c.v.) for 7 days, through pre-implanted cannula using osmotic minipumps (Alzet, model 2ML). The levels of [(3)H]MK-801 binding were highly decreased in part of the parietal layers of the cortex and cingulated by ginsenoside Rc and Rg1. The levels of [(3)H]muscimol binding were strongly elevated in almost all regions of the frontal cortex by the treatment of ginsenoside Rc but decreased by ginsenoside Rg1. However, the [(3)H]flunitrazepam binding was not modulated by ginsenoside Rc or Rg1 infusion. These results suggest that prolonged infusion of ginsenosides could differentially modulate [(3)H]MK-801 and [(3)H]muscimol binding in a region-specific manner.

Animals↗
PubMed1995

Differential modulation by muscimol and baclofen on antinociception induced by morphine, beta-endorphin, D-Pen2,5-enkephalin and U50,488H administered intracerebroventricularly in the mouse.

The present study was designed to investigate the modulatory effects of stimulation of GABAA and GABAB receptors at supraspinal sites on antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. The effects of the GABAA and GABAB receptor agonists, muscimol and baclofen respectively, on the antinociception induced by morphine (a mu-receptor agonist), beta-endorphin (an epsilon-receptor agonist), D-Pen2,5-enkephalin (DPDPE, a delta-receptor agonist) and U50,488H ([trans-3,4-dichloroN-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeocetamide]; a kappa-receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed using the tail-flick and hot-plate tests. Muscimol at doses of 25-200 ng, administered i.c.v. alone did not affect the latencies of tail-flick and hot-plate thresholds, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by i.c.v. administered morphine (2 micrograms), beta-endorphin (1 microgram), DPDPE (10 micrograms), and U50,488H (60 micrograms). Baclofen (1.25-10 ng) administered i.c.v. alone did not affect the latencies of the tail-flick and hot-plate responses, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by beta-endorphin and U50,488H, without affecting morphine- or DPDPE-induced responses. Our results indicate that activation of GABAA receptors at the supraspinal sites by i.c.v. injection of muscimol antagonizes antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. On the other hand, activation of GABAB receptors at supraspinal sites by i.c.v. baclofen antagonizes antinociception induced by i.c.v. administered epsilon- and kappa-opioid agonists, but not mu- or delta-opioid agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Ontogeny of 3H-muscimol binding to membranes of chick forebrain.

A potent GABA agonist, 3H-muscimol, was used to investigate the development of GABA receptors in left and right hemispheres of chick forebrain from day 12 in ovo to day 21 post-hatch. Total specific 3H-muscimol binding (p mol mg-1 protein) increases rapidly in ovo, reaching a peak at around day one post-hatch and then showing a slow decline to approximately 50% of the maximal level at day 21 post-hatch. Despite the considerable evidence from previous studies of lateralization of avian brain function, no significant hemispheric differences were found in 3H-muscimol binding (either of p mol hemisphere-1 or p mol mg protein-1) at any of the developmental ages examined.

Animals↗
PubMed1984

Behavioural responsiveness to muscimol and apomorphine 2 months after prolonged treatment with estradiol in rats.

Two months after prolonged administration of estradiol (ES) in female rats the behavioural responsiveness to muscimol, a GABA receptor stimulating agent, and to apomorphine, a dopamine receptor agonist, was significantly altered. In particular, the decrease in locomotor activity induced by a challenge dose of muscimol (0.5-1 mg/kg) was significantly attenuated in ES-pretreated animals. Conversely, the intensity of stereotyped behaviour elicited by a challenge dose of apomorphine (1 mg/kg) was significantly increased in ES-pretreated rats. The behavioural alterations in the response to muscimol and apomorphine presumably result from the production of central GABA receptor subsensitivity and dopamine receptor supersensitivity respectively, induced by the prolonged ES administration.

Animals↗
PubMed1982

Oral behaviour induced by intranigral muscimol is unaffected by haloperidol but abolished by large lesions of superior colliculus.

It has been suggested that the GAbAergic striatonigral projection may form part of the efferent pathway responsible for the expression of dopamine-related oral behaviour. Consistent with this suggestion are reports that bilateral injection of the GABA agonist muscimol can produce stereotyped gnawing and biting. We report here two experiments on this effect: (1) A dose of the dopamine receptor blocker haloperidol (0.4 mg/kg), which effectively antagonised oral stereotypy induced by systemically administered apomorphine or intranigral carbachol, had no effect on either the latency or the intensity of the gnawing produced by intranigral muscimol (1 nM); (2) large lesions involving the superior colliculus which effectively suppressed the oral stereotypy induced by 8 mg/kg apomorphine completely abolished the gnawing induced by intranigral injection of muscimol. Collicular lesions suppressed both the gnawing which occurred spontaneously and that elicited by a perioral probe. These findings are consistent with the view that the substantia nigra is a relay station between the caudate nucleus and the superior colliculus in an efferent pathway mediating dopamine-related oral behaviour. In addition, they raise the possibility that such behaviour is produced by the sensitisation of a collicular-mediated perioral reflex.

Animals↗
PubMed1980

Development of [3H]muscimol binding to subcellular particles of a culture of mouse brain.

"Specific" binding of [3H]muscimol (11.5 nM) related to GABA receptors, occurred in subcellular particles prepared from 4-, 8-, and 12-day cultures of embryonic (14- to 15-day-old) mouse cerebrum, but not to particles prepared from 20- to 45-day cultures. Phase-contrast microscopy revealed that the presence of neuronal elements (neuroblasts, neurites) paralleled the binding of [3H]muscimol. Further evidence is thus provided for using high-affinity [3H]muscimol binding as a "neuronal marker."

Animals↗