SEARCH · PubMed Health

Results for “Muscimol”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources

PubMed1979

Central antihypertensive properties of muscimol and related gamma-aminobutyric acid agonists and the interaction of muscimol with baroreceptor reflexes.

The central antihypertensive properties of four gamma-aminobutyric acid (GABA) analogs were characterized in anesthetized cats with implanted intracerebroventricular cannulae. An intracerebroventricular infusion (icv) of muscimol, 0.1--0.5 microgram/min (total dose: 1--5 micrograms, icv), substantially reduced mean arterial pressure and slightly reduced heart rate. The compound was not hypotensive at 5 micrograms, iv (total dose) and only slightly hypotensive after an intracisternal injection (5 micrograms). Kojic amine (2-aminomethyl-5-hydroxy-4H-pyran-4-one) and baclofen were also hypotensive following an intracerebroventricular infusion, but they were less active than muscimol. GABA, at 15--150 micrograms/min, icv (total dose, 150--1500 micrograms, icv), was not hypotensive by itself and unlike muscimol its activity was not enhanced in cats pretreated with nipecotic acid, an uptake inhibitor of GABA. The ability of muscimol to interfere with baroreceptor reflexes was considered in experiments in which reflex vasoconstrictor (carotid occlusion) and reflex vasodilatation (acute elevation in mean arterial pressure with norepinephrine) was measured in the perfused hindlimb of cats previously prepared with intracerebroventricular cannulae. Muscimol significantly attenuated the response to bilateral carotid occlusion and completely abolished reflex vasodilatation. The results suggest that GABA agonists and analogs may regulate blood pressure centrally and, through an interaction with the central nervous system, may attenuate baroreceptor reflexes.

Animals↗

PubMed1992

Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the inhibitory GABAA receptor agonist muscimol.

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D[1-14C]glucose technique in the rat brain in order to determine the metabolic effects of unilateral intranigral application of the GABAA agonist muscimol upon the substantia nigra and its targets. Intranigral injection of 1.5 microliters 0.3 M muscimol (52 micrograms total dose) induced local metabolic activation in the injected substantia nigra reticulata (by 87% as compared to the control group), and distal metabolic depressions in the nucleus accumbens, striatum, globus pallidus and subthalamic nucleus only ipsilaterally to the injected nigra. The remaining basal ganglia components, including the substantia nigra compacta and the entopeduncular nucleus were bilaterally unaffected. Among the principal efferent projections of the substantia nigra reticulata, the ventromedial and centrolateral thalamic nuclei as well as the deep layers of the superior colliculi were metabolically depressed bilaterally, whereas the ventrolateral, parafascicular and mediodorsal thalamic nuclei as well as the pedunculopontine nucleus displayed metabolic depressions ipsilateral to the muscimol-injection nigra. The ventromedial and centrolateral thalamic nuclei were depressed by 41 and 42%, respectively, in the ipsilateral side, and by 30 and 26% in the contralateral side, when compared to the respective values of the control group of rats. Furthermore, unilateral intranigral injection of 0.3 M muscimol induced metabolic depressions in reticular, intralaminar and prefrontal thalamocortical areas mostly ipsilateral to the injected nigra, as well as in limbic areas bilaterally. It is suggested that the present findings are due to a postsynaptic effect of muscimol on the nigral GABAergic cells and to a consequent metabolic depression of the basal ganglia and associated thalamocortical areas, in contrast to an earlier suggested presynaptic nigral effect of lower doses of intranigrally injected muscimol which induced metabolic activations within the same network. This suggestion is further supported by the fact that intranigrally injected substrate P19 induced similar effects to those elicited by the lower doses of intranigral muscimol and opposite to those induced at present by the higher muscimol dose. Moreover, it is further substantiated that the nigrothalamic GABAergic system is responsible for considerable transfer of information from one substantia nigra reticulata to the ipsilateral basal ganglia and associated thalamocortical components as well as to bilateral motor, intralaminar and limbic areas.

Animals↗

PubMed1992

Effect of gamma-aminobutyric acid and muscimol on corticosterone secretion in rats.

The effect of gamma-aminobutyric acid-receptor agonists, GABA and muscimol on the pituitary-adrenocortical activity, measured indirectly through corticosterone secretion, and the receptors involved were investigated in conscious rats. GABA given ip induced a dual effect, in lower dose (10 mg/kg) it significantly decreased the resting serum corticosterone levels while in higher doses (100-500 mg/kg) it considerably raised that level. Muscimol (0.5 mg/kg ip) also increased the corticosterone concentration. Both GABA and muscimol given intracerebroventricularly (icv) induced a significant, dose-related increase in serum corticosterone levels. Bicuculline, a GABAA-receptor antagonist, totally abolished the corticosterone response to GABA but did not influence the response to muscimol. Pretreatment with atropine did not affect the corticosterone response to GABA but significantly diminished the response to muscimol. These results suggest that GABA moderately inhibits the pituitary-adrenal axis at the pituitary level but significantly stimulates it at the hypothalamic level. The stimulatory effect of GABA, but not muscimol, is mediated by hypothalamic GABAA-receptors, and in the effect of muscimol hypothalamic cholinergic, muscarinic receptors are involved to a significant extent.

Animals↗

PubMed1979

Baclofen and muscimol: behavioural and neurochemical sequelae of unilateral intranigral administration and effects on 3H-GABA receptor binding.

Log dose-response curves for induction of contralateral rotational behaviour in the rat by unilateral intranigral injections of the GABA agonist muscimol and the GABA analogue baclofen have been compared. Baclofen, 5--1000 ng, produced a maximal rotational response that was only 40% of that produced by 0.25--100 ng muscimol, and log dose-response curves failed to show parallelism. The behavioural effects of both drugs were only weakly antagonised by haloperidol and were not antagonised by 6-hydroxydopamine lesions of ipsilateral dopamine (DA) neurons, indicating that these responses were independent of DAergic mechanisms. The effects of baclofen were weakly antagonised by picrotoxin. Intranigral muscimol and baclofen substantially elevated striatal DA concentrations. While muscimol also substantially elevated striatal dihydroxyphenylacetic acid (DOPAC) but not homovanillic acid (HVA), bactofen did not significantly effect either DOPAC or HVA. Baclofein, GABA and muscimol displaced specific 3H-GABA binding in vitro with IC50's of 40 micron, 400 nM and 40 nM respectively. These results indicate that muscimol and baclofen do not act via a unitary GABAergic mechanism, but suggest that baclofen may be a partial GABA agonist, at least at nigral GABA receptors.

Aminobutyrates↗

PubMed1978

gamma-Aminobutyric acid receptors visualized in spinal cord cultures by [3H]muscimol autoradiography.

gamma-Aminobutyric acid (GABA) receptors were visualized in mouse spinal cord explant cultures by [3H]muscimol autoradiography over certain small neurons of the dorsal horn grey matter, in the interneuronal neuropil of dorsal and ventral horns, and (rarely) in small clusters on processes of anterior horn cells. Specificity was indicated in control experiments by inhibition of binding by [3H]muscimol after pretreatment with GABA or a GABA analogue, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, isoxazole 16), or with receptor antagonists bicuculline and picrotoxin. Unlabeled muscimol exchanged effectively with [3H]muscimol and produced autoradiographic label in locations indistinguishable from those found in experiments with [3H]muscimol alone. Pretreatment with the GABA uptake and transport inhibitors (-)-nipecotic acid and guvacine did not affect binding with [3H]muscimol. These experiments indicate that explant culture systems can be used for demonstration of functional receptors.

Animals↗

PubMed1992

Protection by muscimol against gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in spontaneously hypertensive rats.

The effects of prolonged administration of the gamma-aminobutyric acid receptor agonist muscimol on enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in spontaneously hypertensive rats (SHR), and on the norepinephrine concentration in the gastric wall and the labeling index of gastric mucosa were investigated. SHR and normotensive Wistar Kyoto (WKY) rats as controls were given a solution of MNNG (25 micrograms/ml) for 25 weeks and then i.p. injections of 0.5 mg/kg body weight of muscimol every other day. In control WKY rats, gastric cancers were found in 1 (7%) of 14 rats examined at week 52. In SHR treated with NaCl solution only, the incidence of gastric cancers was significantly increased to 50% compared with that in control WKY rats. However, treatment of SHR with muscimol significantly increased its incidence to 12% compared with the value in SHR treated with NaCl solution only. The norepinephrine concentration in the gastric wall and the labeling index of the gastric mucosa were significantly greater in SHR than in WKY rats. Prolonged administration of muscimol to SHR significantly reduced the norepinephrine concentration in the antral portion of the gastric wall or the labeling index of the antral epithelial cells. These findings indicate that long-term treatment of SHR with muscimol attenuated the enhancement of gastric carcinogenesis in SHR.

Analysis of Variance↗

PubMed1978

Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines.

Intranigral injection of muscimol induced hyperactivity in rats and antagonized haloperidol-induced catalepsy. Intranigral injection of gabaculine, an inhibitor of GABA transaminase, induced similar effects 5h after injection, when the nigral GABA content was increased 7-fold. On the other hand, injections of muscimol (30 ng) into the globus pallidus potentiated the cataleptic effect of haloperidol, and muscimol alone in high doses (100 and 200 ng) induced catalepsy. Gabaculine also induced catalepsy of medium intensity and potentiated the effect of haloperidol 24h after injection, when GABA was increased in the globus pallidus as well as in the substantia nigra. Injections of muscimol into either the globus pallidus or substantia nigra increased striatal HVA and enhanced haloperidol-induced elevation of HVA. Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy. A similar effect was not obtained with phenobarbital. It is suggested that stimulation of GABA receptor or increase of GABA content in the sustantia nigra antagonize haloperidol-induced catalepsy by activation of nigral dopaminergic system, and that enhancement of pallidal GABA function induces catalepsy by non-dopaminergic mechanisms. Potentiation of haloperidol-induced catalepsy by benzodiazepines may be due to enhancement of GABA-ergic transmission within the globus pallidus.

4-Aminobutyrate Transaminase↗

PubMed1992

Muscimol injections into the nucleus basalis magnocellularis of rats: selective impairment of working memory in the double Y-maze.

Anatomical and neurochemical results suggest that the cortico- and amygdalopetal cholinergic neurons of the nucleus basalis magnocellularis (NBM) may receive GABAergic inputs. The present experiments were undertaken to evaluate the possible influence of intra-NBM injections of the GABAA agonist, muscimol, on memory. In two experiments, rats were chronically implanted with guide cannulae placed bilaterally into the NBM. Rats were trained to a criterion of at least 83% correct on each component in a double Y-maze task that allowed a dissociation of working and reference memory. The task began with placement into one of the two end arms of the first Y-maze and the reference memory task was to go to the stem for food. Access to the second Y was then given and the working memory task was to go to the goal arm opposite the arm in the first maze from which that trial began. In experiment 1, pre-trained rats (n = 7) received muscimol (0.5 microliter) in doses of 0, 0.01, 0.1 and 1.0 microgram in a counterbalanced order with re-training to criterion between injections. In experiment 2, pre-trained rats (n = 8) received saline, muscimol (0.1 microgram), the GABAA antagonist, bicuculline (0.01 microgram), and muscimol + bicuculline. Results of experiment 1 revealed that intra-NBM muscimol produced a dose-dependent and differential impairment of working and reference memory. A dose of 0.1 microgram impaired working memory without significantly affecting reference memory; doses of 0.01 microgram and 1.0 microgram affected neither and both types of memory, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1979

Electroencephalographic and behavioral effects of a GABA agonist (muscimol) on photosensitive epilepsy in the baboon, papio papio.

Muscimol, 0.25-1.0 mg/kg, i.v., was administered acutely to 4 adolescent baboons, Papio papio, that show photically induced epilepsy. On the EEG, slowing of background rhythms was associated with the appearance of spikes, polyspikes, and recurring symmetrical spike-wave complexes. These changes were maximal 0.5-2 hr after muscimol injection. Regular testing with intermittent light stimulation showed either no change from control responses or a more severe epileptiform EEG 0.1-3 hr after muscimol. Photically induced myoclonus was not modified by muscimol. Despite its GABA-abonist properties, muscimol is not an effective anticonvulsant.

Animals↗

PubMed1978

Huntington's disease: treatment with muscimol, a GABA-mimetic drug.

Muscimol, a gamma-aminobutyric acid (GABA) analogue that exerts potent and specific agonist effects on GABA receptors, was administered orally to 10 patients with Huntington's disease. In this double-blind study, muscimol treatment did not result in improvement in these patients' motor or cognitive functions. However, muscimol administration did ameliorate chorea in the most severely hyperkinetic patient, and it was associated with the appearance of dystonic features, electroencephalographic changes, and behavioral alterations in some patients. These latter observations support a functional relationship between GABA-ergic activity and the genesis of both systonia and EEG abnormalities in humans. The therapeutic failure of muscimol indicates that the GABA disturbances in Huntington's disease does not alone account for the clinical features of this disorder.

Activities of Daily Living↗

PubMed1979

[Effects of muscimol and diazepam: a comparative study on behavioral inhibiton induced by novelty, punishment, and nonreward (author's transl)].

Diazepam and muscimol, a direct GABA agonist, were compared on behavioral inhibition induced in rats by (1) novelty, (2) punishment, and (3) nonreward. (1) Muscimol (0.03--0.25 mg . kg-1 i.p. 30 min before testing, or i.v. immediately before testing) failed to enhance food intake consistently in a nonfamiliar situation and (0.125--0.5 mg . kg-1 i.p. or i.v.) to increase the ingestion of an unknown food (chocolate); (2) muscimol (0.125--0.5 mg . kg-1 i.p. or 0.25 i.v. 10 min before testing) was ineffective in reducing the inhibition of lever presses for food elicited by the delivery of an electric shock at every eighth press; (3) muscimol (0.125--0.5 mg . kg-1 i.p.) failed to attenuate the inhibitory effects on responding induced by the suppression of the reinforcement during extinction. Contrastingly, diazepam (2 mg . kg-1 i.p. 30 min before testing) was found to reduce each type of behavioral inhibition. These data lend no support to the hypotheses of GABA control of behavioral inhibition and of GABA involvement in the action of benzodiazepines on inhibition induced by novelty, punishment, or nonreward.

Animals↗

PubMed1978

Contralateral turning evoked by the intranigral microinjection of muscimol and other GABA agonists.

Contraversive turning was evoked by the microinjection of GABAergic agents into the substantia nigra (SN) of the rat. Muscimol, the most potent GABA agonist, evoked contralateral turning when injected into the SN in doses of 0.005, 0.05, 0.5 and 5 microgram, whereas 0.5 microgram of muscimol applied at extranigral sites produced no turning. A shorter lived contraversive turning response was evoked by the intranigral micro-injection of imidazole acetic acid (10 or 50 microgram), ethanolamine-O-sulphate (25 or 50 microgram), or GABA (50 microgram). No increase in GABA-induced turning was produced by local pretreatment with pipecolic acid (5 microgram). When injected into the SN, neither picrotoxin, in doses of 0.1, 0.5, 1.0 or 2.0 microgram, nor bicuculline methiodide (Bm), in doses of 0.1 or 0.2 microgram, elicited a significant amount of turning. Picrotoxin, however, partially blocked the turning evoked by the intranigral injection of muscimol, both via the i.p. and intranigral routes of administration whereas Bm did not. In addition, haloperidol (1 mg/kg i.p.) antagonized the muscimol-induced turning. Hence, we feel GABA mimetic substances injected within the SN might evoke contralateral turning via activation of a heretofore undescribed neural system arising from the SN or by activating the ipsilateral dopaminergic neurons projecting from the SN.

Animals↗

PubMed1992

Effect of the beta-adrenoceptor antagonist, propranolol, on feeding induced by noradrenaline and muscimol in rats kept at high and temperate-ambient temperatures.

Both the gamma-aminobutyric acid (GABA) receptor agonist, muscimol, and noradrenaline stimulated the feeding behavior of rats in the two environments. When noradrenaline or muscimol was administered, however, the food intake at 26 degrees C was greater than that at 33 degrees C. In addition, the stimulatory effect of noradrenaline on food intake was significantly depressed by propranolol pretreatment at both temperatures. The stimulatory effect of muscimol on food intake was significantly depressed by the propranolol pretreatment at 33 degrees C but not at 26 degrees C. Some eating-stimulatory subsystems associated with feeding behavior induced by noradrenaline or muscimol might have been depressed in the hot environment, thus the food intake increased by these drugs in rats acclimated to the hot environment was less than that in rats acclimated to the temperate environment.

Animals↗

PubMed1979

The GABA agonist THIP a muscimol analogue, does not interfere with the benzodiazepine binding site on rats cortical membranes.

THIP, a cyclic analogue of muscimol, is a powerful GABA agonist. It is as active as GABA in displacing [3H]muscimol from its binding site to cerebellar membranes (IC50 = 31.5 +/- 2.5 mM). However, unlike muscimol or GABA, it is devoid of any modulatory interaction with the benzodiazepine binding site on rat's cortical membranes. Homotaurine, isoguvacine and imidazole acetic acid are less active than muscimol and GABA for increasing the affinity of [3H]diazepam to cortical membrane preparations.

Animals↗

PubMed1979

Effects of the GABA receptor agonist muscimol on the turnover of brain dopamine and on the motor activity of rats.

Muscimol (3-hydroxy-5-aminomethylisoxazole) at a high dose (10 mg/kg intraperitoneally) elevated the concentration of brain dopamine in rats, decreased the utilization of dopamine and increased the synthesis of dopamine. The utilization of noradrenaline was acclerated rather than retarded by muscimol. Local application of muscimol to the nucleus accumbens of rats inhibited the motor activity in a dose-dependent manner with only a slight subsequent hyperactivity. The effects are similar to those produced by GABA and they support the view that muscimol is a GABA receptor agonist.

Animals↗

PubMed1992

Effect of the GABAA agonist muscimol on prolactin secretion from human prolactin-secreting adenomas and GH3 rat pituitary tumour cells.

The effect of muscimol, a specific potent GABAA receptor agonist, on prolactin release from human prolactin-secreting tissue was investigated using a perifusion system. Perifusion studies on normal rat anterior pituitary tissue, which has identical GABA receptors to those found in normal human pituitary glands, show that muscimol has a specific biphasic effect on prolactin release. This is characterized by an initial transient stimulation (222.3 +/- 21.6% of basal) lasting for 5-10 min followed by a more prolonged inhibitory phase (63.9 +/- 3.1% inhibition of basal). Five human prolactin-secreting adenomas were studied, and in none of the tumours could a biphasic response be demonstrated. One of the prolactin-secreting adenomas had a blunted inhibitory response, but the other 4 showed no inhibitory effect of muscimol on prolactin release. Muscimol had no significant effect on basal or thyrotropin-releasing-hormone (TRH)-stimulated prolactin secretion from GH3 rat pituitary tumour cells. These studies suggest that the GABAergic effect on prolactin secretion is absent or altered in both rat and human prolactin-secreting tumour cells.

Adult↗

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↗

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↗