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At least 19 recordsLinked to original sources
PubMed1984

Muscimol injections in the nucleus raphé dorsalis block the antinociceptive effect of morphine in rats: apparent lack of 5-hydroxytryptamine involvement in muscimol's effect.

The effect of morphine (3 mg kg-1 subcutaneously) on tail flick in the tail immersion test was studied in rats which had received a muscimol (100 ng) injection either in the nucleus raphé dorsalis (DR) or medianus (MR). The levels of 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus and striatum of muscimol-injected animals. Muscimol injections in the DR reduced 5-HIAA concentrations in the striatum but not in hippocampus, whereas in animals which had received muscimol in the MR a selective decrease in hippocampal 5-HIAA levels was found. Muscimol injections in the DR blocked the effect of morphine while no effect was seen in animals which had received muscimol in the MR. An injection of 5,7-dihydroxytryptamine (6 micrograms in 3 microliter) in the DR did not change the effect of morphine or muscimol. These findings indicate that muscimol-sensitive neurones in the DR, which are probably not 5-hydroxytryptaminergic, are involved in the effect of morphine on tail flick in tail immersion. The muscimol-sensitive neurones involved in this effect of morphine do not seem to exist in the MR.

5,7-Dihydroxytryptamine↗
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↗
PubMed1980

Binding and uptake of the GABA analogue, 3H-muscimol, in the retinas of goldfish and chicken.

Gamma-aminobutyric acid (GABA) is a candidate as a neurotransmitter in the vertebrate retina. The GABA analogue muscimol has been used to probe the properties of GABA receptors in other parts of the vertebrate central nervous system (CNS). We thus used 3H-muscimol to investigate potential GABA receptors in the retinas of goldfish and chick by means of biochemical assay techniques and light microscopic autoradiography. In both animals 3H-muscimol shows specific and saturable binding with a dissociation constant (KD) of about 10 nM. GABA effectively inhibits 3H-muscimol binding at 50% inhibitory concentration (IC50) of 10(-6) M. The labeling pattern of 7 x 10(-7) M 3H-muscimol shows common features for both species in that amacrine cell bodies are intensely labeled, horizontal cells are much less so, and there is a laminar pattern throughout the inner plexiform layer (IPL). A 1 mM concentration of GABA abolishes 3H-muscimol labeling in the chick retina and throughout much of the goldfish retina except for some label over amacrine cells and the distal two thirds of the IPL. The intense somatic labeling suggests neuronal uptake of 3H-muscimol, and indeed, virtually all 3H-muscimol labeling is abolished with the addition of 0.4 mM ouabain. The uptake pattern of 3H-GABA differs from that of 3H-muscimol and is largely unaffected by the addition of 1 mM muscimol. We conclude that 3H-muscimol binding in retinas can be adequately demonstrated biochemically but that only 3H-muscimol uptake is observed with autoradiography from tissue conventionally processed through Epon. The fact that GABA can inhibit 3H-muscimol uptake whereas the reverse is not the case shows that the transport carriers for muscimol and GABA are different. Finally, the strong degree of 3H-muscimol uptake by retinal neurons raises serious questions about the use of 3H-muscimol as a probe for GABA synaptic receptors in the retina with autoradiography.

Animals↗
PubMed1999

Concentration-dependent effects of muscimol to enhance pulsatile GnRH release from GT1-7 neurons in vitro.

Immortalized GT1-7 neurons were used to characterize the effect of muscimol, a GABAA receptor agonist, to enhance pulsatile gonadotropin-releasing hormone (GnRH) release. GT1-7 neurons were grown on Cytodex-3 beads and placed in special superfusion microchambers. The cells were superfused at a rate of 6.2 ml x h-1 with Media 199 (pH 7.35) using a commercially available perfusion system. After a pre-muscimol period of 120 min, the cells were exposed for 5 min to 0.35, 1, 5 or 10 microM muscimol or 5 microM muscimol+20 microM of the GABAA receptor antagonist, bicuculline. Following removal of the muscimol (and bicuculline, in the case of the latter experiment), the superfusion was continued for another 115 min. Sample fractions were collected at 5 min intervals throughout the perfusion. Basal GnRH release from the GT1-7 neurons was pulsatile with an average interpulse interval of 45.4+/-0.5 min and an average pulse amplitude of 191.5+/-22.6 pg x min x ml-1. Our results also demonstrated that the GABAA receptor agonist, muscimol, enhances pulsatile GnRH release from GT1-7 neurons in culture. The response to muscimol was saturable and concentration-dependent with an EC50 of 0.47 microM. The effects of 5 microM muscimol to increase GnRH pulsatility were blocked by co-exposure to the GABAA receptor antagonist, bicuculline. The average GnRH interpulse intervals were 41.7+/-1.8 min, 32.5+/-2.9 min, 30.6+/-0.7 min and 25.5+/-0.4 min in the period following exposure to 0.35, 1, 5 and 10 microM of muscimol, respectively (post-muscimol period). GnRH pulse amplitude (mean-area for each pulse) was increased during exposure to muscimol but not during the pre- or post-muscimol periods. The GABAA receptor antagonist, bicuculline, itself had no effect on pulsatile GnRH release. These results are consistent with previously published reports suggesting that activation of the GABAA receptor stimulates hypothalamic GnRH release in embryonic and neonatal animals.

Animals↗
PubMed2006

Binding of muscimol-conjugated quantum dots to GABAC receptors.

Functionalization of highly fluorescent CdSe/ZnS core-shell nanocrystals (quantum dots, qdots) is an emerging technology for labeling cell surface proteins. We have synthesized a conjugate consisting of approximately 150-200 muscimols (a GABA receptor agonist) covalently joined to the qdot via a poly(ethylene glycol) (PEG) linker (approximately 78 ethylene glycol units) and investigated the binding of this muscimol-PEG-qdot conjugate to homomeric rho1 GABAC receptors expressed in Xenopus oocytes. GABAC receptors mediate inhibitory synaptic signaling at multiple locations in the central nervous system (CNS). Binding of the conjugate was analyzed quantitatively by determining the fluorescence intensity of the oocyte surface membrane in relation to that of the surrounding incubation medium. Upon 5- to 10-min incubation with muscimol-PEG-qdots (34 nM in qdot concentration), GABAC-expressing oocytes exhibited a fluorescent halo at the surface membrane that significantly exceeded the fluorescence of the incubation medium. This halo was absent following muscimol-PEG-qdot treatment of oocytes lacking GABAC receptors. Incubation of the oocyte with free muscimol (100 microM-5 mM), PEG-muscimol (500 microM), or GABA (100 microM - 5 mM) substantially reduced or eliminated the fluorescence halo produced by muscimol-PEG-qdots, and the removal of GABA or free muscimol led to a recovery of muscimol-PEG-qdot binding. Unconjugated qdots and PEG-qdots that lacked conjugated muscimol neither exhibited significant binding activity nor diminished the subsequent binding of muscimol-PEG-qdots. The results indicate that muscimol joined to qdots via a long-chain PEG linker exhibits specific binding activity at the ligand-binding pocket of expressed GABAC receptors, despite the presence of both the long PEG linker and the sterically bulky qdot.

Animals↗
PubMed2002

Effectiveness of muscimol-containing microparticles against pilocarpine-induced focal seizures.

PURPOSE: To investigate the efficacy of in situ lipid-protein-sugar particles (LPSPs) in mitigating the epileptogenic and histologic effects of intrahippocampal pilocarpine in rats. METHODS: LPSPs with and without muscimol were produced by spray-drying, sized by Coulter counter, and muscimol content determined by high-pressure liquid chromatography (HLPC). Particles, free muscimol or saline, were injected into the hippocampi of Sprague-Dawley rats before 40 mM pilocarpine, and seizure activity was scored. The trajectories of behavioral scores between groups were compared with two-way repeated measures analysis of variance. Animals were killed after 2 weeks. Brain sections were stained (Timm and thionin) and scored. RESULTS: LPSPs were 4 to 5 microm in diameter, and contained 0 or 2% (wt/wt) muscimol. In vitro, muscimol was released over a 5-day period. Intrahippocampal injections of normal saline and blank LPSPs did not deter seizure activity from pilocarpine. The rise of the trajectory in behavior scores in animals given LPSPs containing 5 microg muscimol was significantly slower than in those receiving saline, blank particles, or 5 microg of unencapsulated muscimol. There was less apparent neuronal injury and CA3 and supragranular mossy fiber sprouting in hippocampi of animals receiving muscimol-containing particles than in animals that did not receive muscimol. Hippocampi of animals that received 5 microg of encapsulated muscimol showed less supragranular sprouting than did those receiving 5 microg of unencapsulated muscimol, but showed no difference in cell loss or CA3 sprouting. CONCLUSIONS: Focally delivered biodegradable microparticles loaded with muscimol are effective in reducing seizure activity from pilocarpine in animals and mitigate the histologic effects.

Animals↗
PubMed1986

Evaluation of the role of antinociception in self-injurious behavior following intranigral injection of muscimol.

In rats, bilateral injection of muscimol (30-60 ng/site) into the medial substantia nigra zona reticulata exerted an antinociceptive effect in the hotplate and tail-flick tests. Injections of muscimol into the substantia nigra also induced intense stereotyped behavior and self-injurious behavior (SIB). Tail-flick and hindpaw-lick responses were inhibited between 30 and 120 min after muscimol, but recovered by 240 min. The antinociceptive responses were not due to motor impairment or ataxia induced by muscimol because a variety of highly-coordinated stereotyped behavioral responses, including rearing, sniffing, head bobbing and licking occurred concurrently. Injection of muscimol into the deep mesencephalic nucleus (DpMcN) also inhibited the tail-flick and hindpaw-lick responses and caused stereotyped behavior but did not induce self-injurious behavior. Injections of muscimol into the substantia nigra, angled (45 degrees) to avoid passing through the deep mesencephalic nucleus, still exerted antinociceptive activity and caused self-injurious behavior. Bilateral microinjections of baclofen (300 ng), 4,5,6,7-tetrahydroisoxazols (5,40c)pyridin-3-ol (THIP; 300 ng), sodium valproate + D,L-diaminobutyric acid (1 microgram), substance P (2.5 micrograms) or D-Pro2-D-Trp7.9-substance P (2.5 micrograms), all suppressed hindpaw-lick responses, although only THIP reduced tail-flick responses. None of these treatments evoked self-injurious behavior. Naloxone (10 mg/kg), picrotoxin (5 mg/kg) or atropine (10 mg/kg) injection of muscimol into the substantia nigra (60 ng) or a single pretreatment with p-chlorophenylalanine diethyl ester (PCPA; 500 mg/kg; 48 hr prior to muscimol) failed to suppress the hindpaw-lick response or self-injurious behavior. These results suggest that the injection of muscimol into the substantia nigra evokes a centrally-mediated antinociception which alone is not sufficient to induce self-injurious behavior. Both antinociception and self-injurious behavior after injection of muscimol into the substantia nigra appear unrelated to cholinergic, serotoninergic, or naloxone-sensitive nociceptive systems; however, the role of activation of gamma-aminobutyric acid (GABA) receptors in these actions of muscimol also remains to be clarified.

Analgesics↗
PubMed1998

Muscimol-like discriminative stimulus effects of GABA agonists in rats.

The discriminative stimulus effects of GABAergic drugs were evaluated in rats trained to discriminate the direct GABA(A) agonist, muscimol (1.0 mg/kg I.P.), from saline under a two-lever fixed ratio (FR) 32 schedule of food reinforcement. Another direct GABA(A) agonist, THIP, produced full substitution for muscimol, however, at doses producing response rate decreasing effects. Diazepam, an allosteric modulator of GABA-mediated postsynaptic inhibition, yielded a maximum of 50% muscimol-lever responding at a dose that also decreased rates of responding. Partial substitution for muscimol (maximal levels of 71% muscimol-lever responding) was also produced by the GABA agonist progabide. Propofol, an anesthetic that potentiates GABA(A) receptor function, and the GABA uptake inhibitor, tiagabine, produced no greater than 53 and 48% muscimol-lever responding, respectively. Valproic acid, a reversible GABA transaminase inhibitor, failed to substitute for muscimol, and vigabatrin, an irreversible GABA transaminase inhibitor, yielded a maximal 46% muscimol-lever responding. These results demonstrate the pharmacological specificity of muscimol discrimination by showing that only direct agonists for the GABA site on the GABA(A) receptor complex produce full substitution. GABA agonists acting by other mechanisms can be distinguished from muscimol and THIP in this procedure.

4-Aminobutyrate Transaminase↗
PubMedDate not supplied

Muscimol changes hypoxia-induced impairment of behavior in rats.

Muscimol, a selective agonist of GABA-A receptors, causes changes in behavioral activity. Hypoxia interferes with the GABAergic system and with the functions of GABA-A receptors. We used muscimol in Wistar rats to estimate its influence on locomotor activity in the open field test as well as on the processes of consolidation and retrieval, evaluated in the test of passive conditioned reflexes. Anxiolytic activity was examined in the elevated "plus" maze in physiological state and after hypoxia-induced amnesia. Following intraperitoneal administration of muscimol (1 mg/kg, ip), the animals showed a decrease in motility, in retrieval of skill reflexes and in a number of entries into open and closed arms in the elevated plus "maze". In animals exposed to hypoxia, we observed reduced motility in the open field, inhibition of retrieval and consolidation of passive conditioned reflexes, shortened time of sojourn in open arms and decreased number of entries into open and closed arms. In the group of animals which underwent hypoxia and then received muscimol, we observed no effect of hypoxia on muscimol activity in the open field test, except rearing when muscimol action was significantly reduced. Muscimol improved consolidation but not retrieval in comparison with the hypoxic saline-treated group of rats. In the elevated "plus" maze test, treatment of rats with muscimol after hypoxia significantly prolonged the time spent in open arms and increased the number of entries into open arms, while shortened the time spent in closed arms. In conclusion, muscimol in hypoxia-exposed group of rats exerted beneficial effect on consolidation in passive avoidance situation and exerted anxiolytic activity. Changes in the activity of muscimol under hypoxia may have significant clinical implications.

Animals↗
PubMed1997

The discriminative stimulus effects of muscimol in rats.

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.

Animals↗
PubMed1988

Autoradiographic localization of muscimol and baclofen binding sites in rodent cingulate cortex.

The laminar distribution of 3H-muscimol and 3H-baclofen binding was analyzed autoradiographically in areas 29c and 24b of rat cingulate cortex. Muscimol binding was heterogeneous in area 29c with a single peak in layer Ia of 320 +/- 26 grains per 2500 micron2. Binding in deeper layers was between 46% and 71% of that in layer Ia. There was a marked diurnal variation in muscimol binding in area 29c such that binding was elevated by 320% in layer Ia of brains perfused at 22:00-01:00 versus those perfused at 11:00-14:00. Muscimol binding in area 24b was uniform across all layers and was higher than that in area 29c except for in layer Ia. Baclofen binding was homogeneous in both areas, but was 120% greater in area 24b than in area 29c, and showed no diurnal variations. To localize muscimol binding sites at the cellular level, two types of lesion experiments were conducted in area 29c. First, ablation of neurons intrinsic to this cortex with the neurotoxin ibotenic acid reduced muscimol binding to homogeneity with a 70% reduction in layer Ia and a 29-42% reduction in deeper layers. Second, knife cuts, which were placed to isolate cingulate cortex from fiber pathways originating extrinsically, increased muscimol binding in all layers except layer Ia. Conversely, knife cuts which isolated superficial from deep layers yielded a marked drop in muscimol binding in all layers. In conclusion, muscimol binding sites are heterogeneously distributed in area 29c with peak binding in layer Ia at night.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Stimulatory effect of muscimol on gastric acid secretion stimulated by secretagogues in vagotomized rats under anesthesia.

The effect of intravenous administration of muscimol, a GABAA receptor agonist, on gastric acid secretion from perfused stomach was studied in vagotomized rats anesthetized with urethane. Muscimol did not stimulate acid secretion by itself. In contrast, muscimol dose dependently potentiated acid secretion induced by pentagastrin, bethanechol and direct vagal stimulation, but not histamine. Muscimol-potentiated acid secretion induced by pentagastrin and bethanechol was not influenced by pretreatment with atropine or cimetidine, respectively. Muscimol-potentiated acid secretion evoked by direct vagal stimulation was prevented by pretreatment with proglumide, a gastrin receptor antagonist. Muscimol-potentiated acid secretion evoked by bethanechol was dose dependently prevented by bicuculline methiodide, suggesting an involvement of peripheral GABAA receptors. These results suggest that muscimol stimulates acid secretion under certain conditions, and that two mechanisms are involved in this effect. The effects of muscimol on acid secretion may be mediated by increasing the release of histamine by pentagastrin, bethanechol and direct vagal stimulation. In addition, muscimol would also be effective if muscarinic agents were already occupying muscarinic acetylcholine receptors on parietal cells.

Anesthesia↗
PubMed1993

Catalepsy induced by muscimol infused into the hypothalamus can be sensitized and is modulated by ovarian steroids.

Muscimol (25 ng), but not saline, infused into the region of the zona incerta and lateral hypothalamus induced significant catalepsy in female rats. Daily administration of muscimol for 5 days resulted in a sensitization of the cataleptic response such that there was a significantly greater response to the same dose of muscimol beginning on Day 3 and continuing to increase up to Day 5. It was determined that the increase in catalepsy across days was not the result of conditioning after an initial exposure to muscimol. The endocrine condition of the female affected the degree of catalepsy induced by the first exposure to intrahypothalamic muscimol. Ovariectomized rats pretreated with estradiol benzoate (EB) exhibited significantly greater catalepsy than did females untreated or treated with progesterone or combined EB and progesterone. Weekly administration of muscimol also produced significant sensitization of the behavioral response, and the degree of sensitization was again affected by endocrine condition. Specifically, although females treated with EB for 2 days before muscimol infusion showed a significantly greater catalepsy after the first infusion than did ovariectomized females, they failed to show any increase in catalepsy scores across the 4 weeks of treatment. The greater catalepsy induced by muscimol infusion in EB-treated females may be related to changes in dopaminergic transmission. In contrast, females pretreated with progesterone 4 hr before muscimol infusion (with or without prior EB) exhibited highly significant increases in cataleptic response across the 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Effects of the putative GABAergic agonists, muscimol and THIP, upon local cerebral glucose utilisation.

The dose-dependent effects of two putative gamma-aminobutyric acid (GABA)-ergic agonists, muscimol and 4,5,6,7-tetrahydroisoxazolo(4,5-e)-pyridin-3-ol (THIP), upon local cerebral glucose utilisation in 60 discrete regions of the CNS have been examined in conscious rats using the [14C]2-deoxyglucose quantitative autoradiographic technique. The intravenous administration of muscimol (0.15-5 mg/kg) and THIP (1-10 mg/kg) resulted in a heterogeneous pattern of significantly reduced glucose utilisation throughout the CNS. The regional hierarchy of changes in glucose utilisation was similar for both muscimol and THIP in all regions (with the exception of the superior colliculus), with muscimol being approximately six times more potent in all regions investigated. The regions in which glucose utilisation was extremely sensitive to change, displaying reductions of approximately 40% following muscimol (1.5 mg/kg) or THIP (10 mg/kg) administration, included all layers of the neocortex (frontal, sensory motor, posterior parietal, primary auditory and visual cortices), the lateral portion of the caudate nucleus, and some thalamic nuclei (lateral geniculate body, mediodorsal and ventrolateral nuclei). Regions displaying more modest reductions in glucose utilisation, approximately 20% following muscimol (1.5 mg/kg) and THIP (10 mg/kg) administration, included most extrapyramidal regions (substantia nigra, pars compacta and reticulata, globus pallidus, subthalamic nucleus, medial portion of the caudate nucleus), a number of cortical and subcortical limbic areas (cingulate and olfactory cortices, hippocampus, nucleus accumbens, anterior thalamus), and medial raphe nucleus. In contrast, in a large number of regions (including cerebellum and related nuclei such as the inferior olivary, red and vestibular nuclei, white matter, pontine reticular formation, hypothalamus, lateral habenula and amygdala), there were only minimal (approximately 10%) reductions in glucose utilisation following muscimol (1.5 mg/kg) and THIP (10 mg/kg) administration. In no region of the CNS was a significant increase in glucose utilisation observed with any concentration of either muscimol or THIP. The regional distribution of alterations in glucose utilisation following muscimol and THIP administration, which does not correspond to the known topography of GABAergic neurones and receptors, provides a comprehensive description of the functional alterations, as reflected in rates of glucose utilisation, that occur in conscious rats after systemic administration of these two putative GABAergic agonists.

Analgesics↗
PubMed1985

Photoaffinity labeling of the GABAA receptor with [3H]muscimol.

Muscimol is one of the most potent agonist ligands at the gamma-aminobutyric acidA (GABAA) receptor. Analysis of its chemical structure showed it to be a candidate for photoaffinity labeling. In practice, UV irradiation at 254 nm both changed the UV spectrum of muscimol and induced an irreversible binding of [3H]-muscimol to rat cerebellar synaptosomal membrane. After 10 min of irradiation, using 10 nM [3H]muscimol, the specific portion of this binding was 270 fmol/mg protein. (Nonspecific binding was defined as that arising in the presence of 1 mM GABA.) Specific binding increased asymptotically up to 100 nM [3H]muscimol. Irradiation of the membranes themselves did not significantly alter the KD or Bmax of reversible [3H]muscimol binding. However, irradiation of [3H]muscimol reduced its capacity subsequently to photolabel the membranes by 86 +/- 3%. Dose-dependent inhibition of binding was observed with muscimol, GABA, and bicuculline methiodide; with 10 nM [3H]muscimol maximum inhibition was 70% of total labeling and the order of potencies of these three compounds was characteristic of labeling to the GABAA receptor. Baclofen, l-glutamate, and diazepam exerted no effect at high concentrations. SDS-PAGE of the photolabeled membranes indicated specific incorporation of radioactivity into two molecular-weight species. One failed to enter the separating gel, implying a molecular weight greater than 250,000 daltons (250 kD). The molecular weight of the other was identified by fluorography to be about 52,000 daltons (52 kD).

Affinity Labels↗
PubMed1980

Circling behavior induced by intranigral injections of GABA and muscimol in rats.

Circling behavior induced by unilateral intranigral injections of GABA or muscimol was studied in rats. Both GABA (10--400 micrograms) and muscimol (1--100 ng) evoked the same kind of contralateral circling behavior dose-dependently when injected into the substantia nigra. Muscinol was much more potent that GABA and its effect lasted longer. Neither GABA nor muscimol induced any ipsilateral circling. Pretreatment with bicuculline (3 mg/kg IP) significantly attenuated the intensity of circling behavior induced by intranigral injections of GABA or muscimol. Pretreatment with haloperidol (0.5 and 1.0 mg/kg SC) also significantly antagonized the circling behavior induced by GABA and muscimol. Pretreatment with atropine (10 mg/kg IP) significantly increased the intensity of circling behavior induced by intranigral injections of muscimol and tended to increase the intensity of circling behavior induced by intranigral injections of GABA. Pretreatment with struchnine (0.25 mg/gk IP) did not modify circling behavior induced by GABA, but did to some extent increase that induced by muscimol. These results indicate that the contralateral circling behavior induced by intranigral injections of GAB and muscimol seems to be dependent both on the activation of the dopaminergic nigrostriatal system and on the nondopaminergic nigral output system.

Animals↗
PubMed1989

Disinhibitory actions of the GABAA agonist muscimol in immature hippocampus.

Bath application of muscimol (10-20 microM) to hippocampal slices obtained from rats on postnatal days 10-15 produced epileptiform activity in the form of multiple population spikes in 20% of slices tested, concurrent with marked disinhibition. The disinhibition occurred in nearly 100% of cases tested at muscimol concentrations that produced epileptiform activity. Paired pulse analysis of GABAergic recurrent inhibition revealed a muscimol-induced disinhibitory effect involving a decrease in maximum possible inhibition. Spontaneous and antidromically elicited inhibitory postsynaptic potentials (IPSPs) recorded intracellularly were suppressed by muscimol. Current-voltage analysis of the recurrent IPSPs suggests that muscimol acted at a number of sites to produce disinhibition. The input conductance of the postsynaptic pyramidal cell increased due to muscimol, creating a current shunt which likely decreased the efficacy of synaptic currents. Muscimol also caused a decrease in the conductance due to the IPSP as well as a shift in the depolarizing direction of the equilibrium potential of the IPSP. The data indicate that muscimol, a GABAA agonist, can produce disinhibition resulting from the multiple consequences of its action. We conclude that the physiologic consequences of GABAA agonist treatment are complex. On the other hand, neurons are likely to be inhibited by a tonic increase in membrane conductance. However, since recurrent inhibition is simultaneously compromised, excitatory vollies of sufficient intensity may overcome the tonic inhibition and produce a hyperexcitable state. In some cases, this disinhibition may induce epileptiform activity. These observations are relevant in light of the proposed use of GABA agonists clinically to control seizures.

Animals↗
PubMed1995

Muscimol induces state-dependent learning in Morris water maze task in rats.

Effects of muscimol on the place learning in Morris water maze task were investigated in rats. Rats were given 4 training trials per day with the submerged platform at a fixed location in the maze for 4 days. On day 4, rats were required to swim in the pool without the platform after 4 training trials (probe test). Compared to the saline-treated rats, the rats treated with muscimol on day 1-4 showed no modifications of place learning in the training trials and the probe test. However, in the rats treated with muscimol on day 1-3 and treated with saline on day 4, there was increased latency to reach the platform and reduced duration in the quadrant where the platform had been located on day 4. The increased latency in the training trials and reduced duration in the probe test on day 4 was blocked by bicuculline, when bicuculline and muscimol were co-administered on day 1-3, and saline was injected on day 4. Moreover, in the rats treated with muscimol on day 1-3, co-administration of bicuculline and muscimol on day 4 blocked place learning: increased latency in the training trials and reduced duration in the probe test was observed. These results suggest that muscimol induces state-dependent learning (SDL) in Morris water maze task, and that muscimol-induced SDL is mediated by GABAA receptors.

Animals↗