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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↗
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↗
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↗
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↗
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↗
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↗
PubMed1991

Differential effects of bicuculline and muscimol microinjections into the vestibular nuclei on simian eye movements.

1.) Eye movements were recorded in four Java monkeys (M. fascicularis) after unilateral microinjections (1 microliter, concentration 1 micrograms/microliter) of the GABA antagonist, bicuculline, and the GABA agonist, muscimol, into oculomotor related regions of the vestibular nuclei. Eye movements were investigated in the dark and light during spontaneous eye movements, vestibular stimulation (sinusoidal: 0.2 Hz, +/- 40 deg/s, and velocity trapezoid: 40 deg/s2 acceleration, 120 deg/s constant velocity), and visual-vestibular conflict stimulation. 2.) Bicuculline and muscimol injections consistently led to specific eye movement changes, which were maximal 5-10 min after bicuculline injection (muscimol 10-30 min), and lasted 90-120 min (muscimol 2-4 h). Control injections with NaCl (0.9%) into the responsive area and with bicuculline 2-3 mm more lateral showed no effect. 3.) Bicuculline induced a spontaneous nystagmus of 40.9 deg/s (average, range 10.5-93 deg/s), beating in 60% of the cases to the contralateral and in 40% to the ipsilateral side. The analysis of the slope of the slow phase gave no evidence for an additional gaze holding deficit. The VOR gain in the dark showed a slight decrease (pre: 0.96; post: 0.86) on average. The time constant of decay for slow phase nystagmus velocity after vestibular ramp stimulation was reduced, reflecting a 'velocity storage' deficit. After bicuculline injections nystagmus suppression in the light and during visual-vestibular conflict stimulation was generally well preserved. 4.) After muscimol injections horizontal gaze holding was severely affected. Each saccade was followed by an exponentially decreasing postsaccadic drift with a time constant as short as 250 ms (average 414 ms). The eyes always drifted towards a null-position, which generally did not coincide with the midposition of the eye. The null-position could move up to 35 deg to the contralateral or ipsilateral side. The highly distorted eye movements after muscimol injections prevented VOR-measurements based on eye velocity. Instead vestibular stimulation led to a shift of the null-position with an amplitude corresponding to a gain (eye position/stimulus position) of 0.17 (average) at 0.2 Hz (+/- 40 deg/s). Vertical eye movements did not show a major gaze holding deficit. 5.) From the experiments it can be concluded that the inhibitory transmitter GABA plays an important role for eye movement generation within the vestibular nuclei. Bicuculline induces mainly a vestibular imbalance with little evidence for a neural integrator deficit. In contrast unilateral muscimol injections lead to a complete, reversible loss of function for the common horizontal neural integrator, which converts eye velocity into eye position signals. The accompanying shift of the null-position reflects an additional vestibular imbalance.

Animals↗
PubMed1986

Involvement of the midbrain reticular formation in self-injurious behavior, stereotyped behavior, and analgesia induced by intranigral microinjection of muscimol.

Bilateral microinjection of muscimol (60 ng), a gamma-aminobutyric acid (GABA) agonist, into the central region of the substantia nigra (pars reticulata) produced self-injurious behavior (SIB), stereotyped behavior and analgesic-like effects in rats. Bilateral electrolytic lesions of the midbrain reticular formation ventrolateral to the periaqueductal gray matter completely blocked the SIB but had little effect on stereotyped behavior produced by intranigral muscimol. Lesions of the midbrain reticular formation reduced the antinociceptive effect of intranigral muscimol on the tail-flick but not on the hot-plate test. Bilateral microinjection of muscimol (10-100 ng) into the midbrain reticular formation produced intense stereotyped behavior and had an analgesic-like effect on the hot-plate test but not on the tail-flick test. Stereotyped behavior appeared to interfere with the paw-lick response on the hot-plate test. These data suggest that the antinociceptive effect of intranigral muscimol on the tail-flick test is mediated by fibers that project to or pass through the midbrain reticular formation and that analgesia may play an important role in muscimol-induced SIB. The midbrain reticular formation does not appear to be involved in the stereotyped behavior produced by intranigral muscimol.

Animals↗
PubMed1985

Modification of saccadic eye movements by GABA-related substances. I. Effect of muscimol and bicuculline in monkey superior colliculus.

Our previous observations led to the hypothesis that cells in the substantia nigra pars reticulata (SNr) tonically inhibit saccade-related cells in the intermediate layers of the superior colliculus (SC). Before saccades to visual or remembered targets, cells in SNr briefly reduce that inhibition, allowing a burst of spikes of SC cells that, in turn, leads to the initiation of a saccadic eye movement. Since this inhibition is likely to be mediated by gamma-aminobutyric acid (GABA), we tested this hypothesis by injecting a GABA agonist (muscimol) or a GABA antagonist (bicuculline) into the superior colliculus and measured the effects on saccadic eye movements made to visual or remembered targets. An injection of muscimol selectively suppressed saccades to the movement field of the cells near the injection site. The affected area expanded over time, thus suggesting the diffusion of muscimol in the SC; the area never included the other hemifield, suggesting that the diffusion was limited to one SC. One of the monkeys became unable to make any saccades to the affected area. Saccades to visual targets following injection of muscimol had longer latency and slightly shorter amplitudes that were corrected by subsequent saccades. The most striking change was a decrease in the peak velocity of the saccade, frequently to less than half the preinjection value. Saccades to remembered targets following injection of muscimol also showed an increase in latency and decrease in velocity, but in addition, showed a striking decrease in the accuracy of the saccades. The trajectories of saccades became distorted as if they were deflected away from the affected area. After muscimol injection, the area over which spontaneous eye movements were made shifted toward the side ipsilateral to the injection. Saccades toward the contralateral side were less frequent and slower. In nystagmus, which developed later, the slow phase was toward the contralateral side. In contrast to muscimol, injection of bicuculline facilitated the initiation of saccades. Injection was followed almost immediately by stereotyped and apparently irrepressible saccades made toward the center of the movement field of the SC cells at the injection site. The monkeys became unable to fixate during the tasks; the fixation was interrupted by saccadic jerks made to the affected area of the visual field and then back to the fixation point.(ABSTRACT TRUNCATED AT 400 WORDS)

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↗
PubMed1989

Central administration of muscimol phase-shifts the mammalian circadian clock.

The suprachiasmatic nucleus (SCN) of the hypothalamus contains a neural oscillatory system which regulates many circadian rhythms in mammals. Immunohistochemical evidence indicates that a relatively high density of GABAergic neurons exist in the suprachiasmatic region. Since intraperitoneal injections of the benzodiazepine, triazolam, have been shown to induce phase shifts in the free-running circadian rhythm of locomotor activity in the golden hamster, the extent to which microinjections of muscimol, a specific agonist for gamma-aminobutyric acid (GABA), may cause phase-shifts in hamster activity rhythms was investigated. Stereotaxically implanted guide cannulae aimed at the region of the SCN were used to deliver repeated microinjections in individual animals. A phase-response curve (PRC) generated from microinjections of muscimol revealed that the magnitude and direction of permanent phase-shifts in the activity rhythm were associated with the time of administration. The PRC generated for muscimol was characterized by maximal phase-advances induced 6 h before activity onset and by maximal phase-delays which occurred 6 h after activity onset. The PRC for muscimol had a shape similar to a PRC previously generated for the short-acting benzodiazepine, triazolam. Single microinjections of different doses of muscimol given 6 h before activity onset induced phase-advances in a dose-dependent fashion. Histological analysis revealed that phase shifts induced by the administration of muscimol were associated with the proximity of the injection site to the SCN area. These data indicate that a GABAergic system may exist within the suprachiasmatic region as part of a central biological clock responsible for the regulation of the circadian rhythm of locomotor activity in the golden hamster.

Animals↗
PubMed1990

Ontogeny of muscimol effects on locomotor activity, habituation, and pain reactivity in mice.

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)

Aging↗
PubMed1987

Behavioural and electrocortical changes induced by muscimol in rats withdrawn from chronic treatment with diazepam.

In rats withdrawn from a chronic treatment with diazepam, the effects of muscimol, given into the III cerebral ventricle, on behaviour and spectrum power of activity in the electrocorticogram (ECoG) were studied. In comparison to control rats which received only muscimol, in rats pretreated with diazepam (1 mg/kg/day for 30 consecutive days) the behavioural and ECoG effects of muscimol were significantly reduced or abolished. In fact, in rats pretreated with diazepam a small dose (50 ng) of muscimol did not affect behaviour or ECoG activity, in contrast to control animals in which the same dose produced, after a period of locomotor stimulation and ECoG desynchronization, typical and long-lasting behavioural sedation or sleep accompanied by a significant increase in total voltage power and in the lower frequency bands in the ECoG. In addition, larger doses (100 and 200 ng) of muscimol, which in control rats produced a typical biphasic pattern of ECoG and behavioural changes, i.e. an initial period of ECoG desynchronization and behavioural stimulation, followed by a second period of behavioural and ECoG sleep, in animals pretreated with diazepam, produced only an increase in total voltage power and in the lower frequency bands in the ECoG resembling the effects of the smaller (50 ng) dose. The present experiments suggest that, after chronic stimulation of benzodiazepine receptors a decrease in sensitivity of receptors for gamma-aminobutyric acid (GABA) occurs, since the effects of muscimol on behaviour and spectrum power were significantly reduced or abolished.

Animals↗
PubMed1990

Modulation by estrogen and progesterone of the effect of muscimol on nociception in the spinal cord.

The GABAA agonist, muscimol, administered intrathecally (IT) to the spinal cord at a dose (1 microgram) that was subthreshold for affecting pain thresholds (vocalization-threshold-to-tail-shock: VTTS, and tail-flick latency: TFL) in ovariectomized, hormonally untreated rats, showed a significant increase in VTTS up to 30 min postinjection in intact females only in proestrus or estrus. This treatment produced no significant effect on TFL at any stage of the estrous cycle. IT muscimol produced a significant increase in VTTS (but not TFL) in ovariectomized rats primed with estradiol benzoate (EB) for 2 days and tested 40 hr after the second injection but had no effect in females primed with a single EB injection and tested 15 min later. By contrast, ovariectomized females primed with progesterone (P) for 15 min exhibited a significant increase in pain thresholds after IT muscimol in both the VTTS and TFL tests. When EB-primed females (2 days) received P 4 hr prior to muscimol there was no analgesia produced by IT muscimol, in contrast to EB-primed females receiving P 15 min prior to IT muscimol in which there was significant analgesia. These results suggest a mechanism for antagonistic effects of estrogen and progesterone.

Animals↗
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↗
PubMed1989

Binding of [3H]-muscimol to GABAA sites in the guinea-pig urinary bladder: biochemical assay and autoradiography.

1. The specific binding of [3H]-muscimol, a gamma-aminobutyric acidA receptor (GABAA) agonist, to whole membranes of the guinea-pig urinary bladder was examined. In addition, the distribution of specific muscimol binding sites within the bladder was visualized by autoradiography. 2. It was demonstrated that in a frozen-thawed whole membrane preparation of the organ the specific binding of [3H]-muscimol is reproducible, reversible and saturable. 3. Saturable binding was of a single component with an equilibrium dissociation constant (Kd) of 12 nM and a maximal density (Bmax) of about 80 fmol mg-1 protein. 4. In displacement experiments with several model compounds, [3H]-muscimol binding sites showed the characteristics of a GABAA receptor site. 5. Autoradiographic experiments revealed uneven distribution of specifically bound [3H]-muscimol in the bladder. The density of binding sites was high in clusters within the smooth muscle layers of the bladder fundus and of the urethra, while the apex and the neck were not specifically labelled. 6. The present findings show that GABAA type receptor sites in the guinea-pig urinary bladder may be labelled by [3H]-muscimol in a specific and reproducible manner. Moreover, the localization of these binding sites is consistent with the presence of GABAA receptors in only a subpopulation of vesical ganglia.

Animals↗
PubMed1988

Comparison between pentobarbital- and muscimol-induced feeding in satiated sheep.

Twenty sheep were used to study the mechanisms by which the intracerebral administration of pentobarbital and of muscimol induces feeding in ruminants. Injections of 1 mumol calcium induced a weak feeding response at 1 h postinjection compared with control values (108 vs. 63 g, p less than 0.05). Injections of 78 mumol pentobarbital and of 100 nmol muscimol elicited strong feeding responses (p less than 0.01). A preinjection of 1 mumol calcium reduced the response to pentobarbital by about 40% but did not affect the response to muscimol. Administration of 1.1 mmol sodium chloride reduced the effect to pentobarbital by about 60% but only partially decreased the effect to muscimol. Administration of picrotoxin, a GABA antagonist, slightly decreased the feeding response to pentobarbital and to muscimol. Administration of gamma-vinyl GABA, an inhibitor of the enzyme GABA transaminase, did not affect feeding behavior of sheep at any of the doses tested (0-10 mumol). Injections of gamma-vinyl GABA followed by equimolar injections of GABA failed to provoke any feeding response. The data suggest that pentobarbital and muscimol may induce feeding by acting on a similar hypothalamic receptor complex but by different mechanisms. The lack of effect of GABA itself remains unexplained.

Aminocaproates↗