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At least 217 records · Page 12Linked to original sources
PubMed1998

Orienting gaze shifts during muscimol inactivation of caudal fastigial nucleus in the cat. II. Dynamics and eye-head coupling.

We have shown in the companion paper that muscimol injection in the caudal part of the fastigial nucleus (cFN) consistently leads to dysmetria of visually triggered gaze shifts that depends on movement direction. Based on the observations of a constant error and misdirected movements toward the inactivated side, we have proposed that the cFN contributes to the specification of the goal of the impending ipsiversive gaze shift. To test this hypothesis and also to better define the nature of the hypometria that affects contraversive gaze shifts, we report in this paper on various aspects of movement dynamics and of eye/head coordination patterns. Unilateral muscimol injection in cFN leads to a slight modification in the dynamics of both ipsiversive and contraversive gaze shifts (average velocity decrease = 55 degrees/s). This slowing in gaze displacements results from changes in both eye and head. In some experiments, a larger gaze velocity decrease is observed for ipsiversive gaze shifts as compared with contraversive ones, and this change is restricted to the deceleration phase. For two particular experiments testing the effect of visual feedback, we have observed a dramatic decrease in the velocity of ipsiversive gaze shifts after the animal had received visual information about its inaccurate gaze responses; but virtually no change in hypermetria was noted. These observations suggest that there is no obvious causal relationship between changes in dynamics and in accuracy of gaze shifts after muscimol injection in the cFN. Eye and head both contribute to the dysmetria of gaze. Indeed, muscimol injection leads to parallel changes in amplitude of both ocular and cephalic components. As a global result, the relative contribution of eye and head to the amplitude of ipsiversive gaze shifts remains statistically indistinguishable from that of control responses, and a small (1.6 degrees) increase in the head contribution to contraversive gaze shifts is found. The delay between eye and head movement onsets is increased by 7.3 +/- 7.4 ms for contraversive and decreased by 8.3 +/- 10.1 ms for ipsiversive gaze shifts, corresponding respectively to an increased or decreased lead time of head movement initiation. The modest changes in gaze dynamics, the absence of a link between eventual dynamics changes and dysmetria, and a similar pattern of eye-head coordination to that of control responses, altogether are compatible with the hypothesis that the hypermetria of ipsiversive gaze shifts results from an impaired specification of the metrics of the impending gaze shift. Regarding contraversive gaze shifts, the weak changes in head contribution do not seem to reflect a pathological coordination between eye and head but would rather result from the tonic deviations of gaze and head toward the inactivated side. Hence, our data suggest that the hypometria of contraversive gaze shifts also might result largely from an alteration of processes that specify the goal rather than the on-going trajectory, of saccadic gaze shifts.

Analysis of Variance↗
PubMed2002

Inhibition of muscimol on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity.

This study was performed to investigate the effect of muscimol on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity as measured in mice, and the morphine-induced hyperactivity was inhibited dose-dependently by the administration of the GABA(A) agonist, muscimol (0.3, 0.5 and 1.0 mg kg(-1) i.p.). However, daily repeated administration of morphine caused the development of reverse tolerance against morphine hyperactivity (10 mg kg(-1) s.c.). The administration of muscimol inhibited the development of reverse tolerance against morphine hyperactivity (10 mg kg(-1) s.c.) in mice that had received chronic administration of morphine. Postsynaptic dopamine receptor supersensitivity, as shown by the enhanced ambulatory activity after administration of apomorphine (2 mg kg(-1) s.c.), also developed in reverse-tolerant mice. Muscimol also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited via the activation of GABA(A) receptors.

Animals↗
PubMed1993

Chronic administration of muscimol and pentobarbital decreases gonadotropin-releasing hormone mRNA levels in the male rat hypothalamus determined by quantitative in situ hybridization.

The role of GABA in the control of gonadotropin-releasing hormone (GnRH) secretion is still controversial. In order to investigate the role of the GABAergic system in the regulation of GnRH gene expression in the rat brain, we studied the effects of chronic administration (2 days) of the GABAA receptor agonist muscimol and the central-type barbiturate receptor agonist pentobarbital on GnRH mRNA levels measured by in situ hybridization. Treatment with pentobarbital produced a 24% decrease in the hybridization signal. Similarly, muscimol treatment decreased the signal by 28%. The concomitant administration of the two GABAA receptor agonists resulted in a decrease (37%) of mRNA levels which was significantly more marked than that induced by pentobarbital or muscimol alone. The present results, together with previous data, indicate that the administration of pentobarbital or muscimol can inhibit not only the release of GnRH but also the gene expression of the neuropeptide as evaluated by mRNA level measurements.

Animals↗
PubMed1988

Autoradiographic localization of the GABAA receptor agonist [3H]-muscimol within rat kidney.

By the use of combined radioreceptor binding and autoradiographic techniques, the pharmacological characteristics of (3H)-muscimol binding and the localization of the label were studied. (3H)-Muscimol was bound by sections of rat kidney in a manner consistent with the existence of specific gamma-aminobutyric acid 'A' (GABAA) receptors with KD and Bmax values of 23.7 nmol/l and 1.15 pmol/mg tissue, respectively. (3H)-Muscimol was bound by convoluted tubules of the renal cortex and by the collecting tubules. Our findings demonstrating the existence of recognition sites for the GABAA receptor agonist muscimol in the kidney suggest that GABA has a role in renal function.

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↗
PubMed1984

Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis.

The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist muscimol (0.01-1 microgram) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 +/- 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of -52.7 +/- 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatment with atropine (2 mg/kg, ip, or 15 micrograms/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 +/- 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was -12.1 +/- 1.6 mm Hg from 109.3 +/- 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats, Following 1 microgram muscimol, icv, plasma noradrenaline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 +/- 24.2 to 22.8 +/- 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 microgram muscimol, icv.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1997

Medical therapy for intracerebral hematoma with the gamma-aminobutyric acid-A agonist muscimol.

BACKGROUND AND PURPOSE: No therapy has been rigorously proven effective for intracerebral hematoma, although surgery is frequently used for some types of lobar hemorrhages. Since intracerebral mass causes significant ischemia in surrounding brain, we reasoned that anti-ischemia therapy might improve outcome after experimental hematoma. METHODS: We stereotaxically injected varying doses of bacterial collagenase into the caudate nucleus of rats. Four hours later we administered intravenously 2 mg/kg muscimol, a potent agonist of the gamma-aminobutyric acid-A receptor (n = 20); 1 mg/kg MK-801, an antagonist of the N-methyl-D-aspartate receptor (n = 17); or saline (n = 28). Forty-eight hours after collagenase injection we rated each animal using a standard rodent neurological examination. The ratings were compared with the amounts of injected collagenase by the quantal bioassay procedure. Brains were then prepared for histomorphometry and brain volumes estimated. RESULTS: We found that the ED50 for collagenase (amount of enzyme that renders 50% of the subjects abnormal) was 0.77 +/- 0.09 U in saline-treated subjects. Treatment with muscimol significantly increased the ED50 to 1.2 +/- 0.21 U, for a potency ratio of 1.55 +/- 0.34 (t = 1.7, P < .05). MK-801 did not affect outcome. Volume of hematoma was significantly correlated with amount of injected collagenase (n = 33, r = .64, P < .001). Volumes of basal ganglia and white matter were significantly reduced by hemorrhage, and muscimol partially ameliorated this. CONCLUSIONS: We conclude that muscimol significantly improves neurological outcome after intracerebral hematoma.

Animals↗
PubMed1980

Anticonvulsant effects of muscimol.

Muscimol is a potent agonist at GABA-inhibitory synapses in mammalian brain. Given systemically at 7 mumol per kilogram, it blocks topical penicillin seizures and delays the onset of generalized metrazol convulsions in rats. It has no effect against generalized seizures caused by picrotoxin or strychnine. Higher doses of muscimol cause bradykinesia, ataxia, catatonic posturing, and slowing of the electroencephalogram. When applied topically to cortex, muscimol blocks focal penicillin, bicuculline, and picrotoxin discharges in a dose-response relationship. It has no effect against topical strychnine. Muscimol offers a potential new approach to the treatment of epilepsy.

Animals↗
PubMed1981

The ventromedullary hypotensive effect of muscimol in the anaesthetized cat.

Muscimol, a rigid analogue of GABA, was injected into the CNS of urethane-anaesthetized, normotensive cats. Bilateral microinjections of a small dose of muscimol (100 ng/kg, 0.5 microliter on each side) in the nucleus reticularis lateralis (NRL) induced hypotension. The marked fall in blood pressure obtained by injecting 1 microgram/kg of muscimol unilaterally into the NRL is completely reversed by subsequent local administration of bicuculline (5 microgram/kg, 0.5 microliter), a specific GABA antagonist. These data confirm that a GABAergic inhibitory system modulates the pressor tonic structures localized in the region of the NRL and that the anteroventral part of the medulla oblongata includes a trigger zone for the hypotensive action of muscimol.

Anesthesia↗
PubMedDate not supplied

Alcohol intake and brain [3H]muscimol binding sites in alcohol-preferring and non-preferring rats.

The present study has employed in vitro autoradiography to determine the distribution and density of [3H]muscimol binding sites in the brains of alcohol high-preferring line of rats (WHP) and alcohol low-preferring line of rats (WLP). While the density of [3H]muscimol binding was found to be similar in the frontal cortex, caudate-putamen, nucleus accumbens, lateral and medial septum, the density of [3H]muscimol binding was lower in cingulate cortex of alcohol low-preferring rats as compared to alcohol high preferring rats. Moreover, the density of muscimol binding sites within this area was positively correlated with the intensity of ethanol consumption.

Alcohol Drinking↗
PubMed1990

Autoradiographic localization of receptor sites of 3H-muscimol in the CNS of rats.

Radiolabelled muscimol (3-hydroxy-5-aminomethylisoxazole) a potent gamma-amino-butyric acid (GABA) agonist was continuously perfused throughout intraventriculocisternal system of the rat brain. Then the brain tissue was prepared for autoradiography. GABA receptor sites as indicated by 3H-muscimol binding and autoradiographic silver grains display different patterns of distribution over numerous cerebral and spinal cord structures. The precise cellular localization of 3H-muscimol in rat neostriatum was described and compared with other labelled regions of rat brain. The new subpopulations of local neostriatal medium size neurons labelled by 3H-muscimol was identified. The morphology and distribution of the specific neuron subpopulation is discussed. Autoradiographic approach using synthetic analogues structurally related to GABA represent a new tool for morphological demonstration of GABA receptor sites.

Animals↗
PubMed1990

Butyrylcholinesterase fluctuation in male albino rats with intracerebroventricular injection of gamma aminobutyric acid, muscimol, and picrotoxin.

The effects of intracerebroventricular injection of gamma-Aminobutyric acid, muscimol, or picrotoxin have been studied on butyrylcholinesterase (BuChE) activities in the serum and several hypothalamic nuclei using biochemical, histochemical, and cytophotometric techniques, respectively. The blood samples were withdrawn from indwelling catheters in jugular vein 1, 15, 30, 45, 60, 90, and 120 min after injection of the drugs. Biochemical estimations demonstrated a significant inhibition of BuChE after GABA and muscimol injections, whereas a pronounced stimulation of BuChE was observed after injection of picrotoxin. The peak changes were observed within 30 min of drug injection. Cytophotometric studies have appeared to dovetail the biochemical findings. Only a marginal decrease was observed after injection of GABA in all nuclei, while muscimol induced a very conspicuous decrease of BuChE. On the contrary, intracerebroventricularly administered picrotoxin markedly increased the levels of BuChE activity. Thus it could be concluded that probably GABA and muscimol along with picrotoxin appear to alter BuChE.

Animals↗
PubMed1989

Muscimol, gamma-aminobutyric acidA receptors and excitatory amino acids in the mouse spinal cord.

These experiments examined the effects of intrathecally administered gamma-aminobutyric acid (GABA) agonists on the effects of intrathecally administered excitatory amino acid (EAA) agonists: N-methyl-D-aspartic acid (NMDA), quisqualic acid and kainic acid. We have found that muscimol, a GABAA receptor agonist, but not baclofen, a GABAB receptor agonist, dose-dependently inhibited caudally directed biting and scratching behavior induced by all three EAA agonists. This nonselective blockade of the expression of effects mediated by all three types of EAA receptor is in marked contrast to the selective blockade of NMDA effects seen previously in the case of mu opioids and phencyclidine receptor agonists. Inhibition by muscimol was blocked with the GABAA receptor antagonist, bicuculline. Decreased latency or hyperalgesia in the tail-flick test, found previously to be induced selectively by NMDA and blocked by an NMDA receptor antagonist, was similarly affected by muscimol but not baclofen, each given intrathecally. However, muscimol prolonged the tail-flick latency only after presentation of NMDA suggesting a possible antinociceptive effect of GABAA agonists in the presence of agonists at NMDA receptors. This study together with the preceding paper resolves GABA-mediated spinal antinociception into two components: a GABAA agonist selectively blocks nociception involving EAA receptors whereas a GABAB agonist selectively blocks substance P spinal activity (the preceding paper).

Analgesia↗
PubMed1989

Qualitative and quantitative changes in monoamine oxidase activity after acute third ventricle treatment of GABA, muscimol, and picrotoxin in rat.

The effect of acute IIIrd ventricle injection of GABA, muscimol, and picrotoxin on the activity of monoamine oxidase (MAO) has been investigated in serum and a few hypothalamic nuclei of the rat brain using biochemical, histochemical, and cytophotometric techniques. Biochemical estimation demonstrated a significant reduction in MAO enzyme activity after GABA and muscimol injection, whereas picrotoxin produced pronounced increase in the enzyme activity. Histochemical and cytophotometric studies confirmed the biochemical findings. Even in brain, GABA and muscimol inhibited and picrotoxin stimulated the MAO activity. From the above findings, it may be concluded that GABA, muscimol, and picrotoxin regulate the MAO activity, possible mechanisms for which are being discussed.

Animals↗
PubMed1988

Sensitivity of embryonic spontaneous motility to the GABA agonists baclofen and muscimol.

The development of the sensitivity of spontaneous motor activity to the GABA agonists baclofen (10 mg/kg egg weight, systemic administration) and muscimol (0.8 mg/kg e.w., systemic administration) was tested in 11-day to 19-day-old chick embryos. 1) Baclofen already significantly depressed the frequency of spontaneous movements in 11-day embryos; its effect attained the maximum (85% depression of spontaneous motility) in 13-day embryos. After the 15th day of incubation, it reduced spontaneous motor activity by 50-60%. In spinal embryos, baclofen had the same, but a quantitatively more pronounced effect, demonstrated from its direct action on the spinal cord uninfluenced by supraspinal modulation, which began to be manifested after the 15th day of incubation. 2) Muscimol did not begin to inhibit spontaneous motility significantly until the 13th day of incubation. Subsequently, the latent period of its effect shortened, its duration lengthened and, lastly, its quantitative result also increased. 3) A comparison of the effect of GABA (Sedlácek 1978), muscimol and baclofen in 17-day chick embryos showed that the depressive effect increased in the sequence baclofen less than GABA less than muscimol, but that GABA took effect faster than the others. The results testify that the maturation of the individual elements of the GABA-ergic central inhibition system is a complex process.

Animals↗
PubMed1985

Benzodiazepines enhance the muscimol-dependent activation of phospholipase A2 in glioma C6 cells.

Glioma C6 cells were incubated with [14C]arachidonate to label membrane phospholipids. Muscimol, a selective gamma-aminobutyric acid A receptor agonist, but not (-)-baclofen, a selective gamma-aminobutyric acid B receptor agonist, stimulates [14C]arachidonate release from C6 cells as a result of hydrolysis of a small pool of phosphatidylcholine and phosphatidylethanolamine by phospholipase A2. This release is facilitated by diazepam and a number of other benzodiazepines such as flunitrazepam, medazepam and midazolam (but very little by clonazepam), although these benzodiazepines per se are inactive in causing the release. In addition to increasing the release of [14C]arachidonate, diazepam in the presence of muscimol promotes the release of [14C] prostaglandin D2. Bicuculline inhibits the action of muscimol and facilitation by diazepam. "Peripheral" benzodiazepine ligand, RO 5-4864 (4'-chlordiazepam) antagonizes the action of diazepam, whereas "central" ligand, RO 15-1788, is inactive. The release of arachidonate metabolites stimulated by muscimol and diazepam is unaffected by Cl- channel blockers, picrotoxin and pentylenetetrazol. Based on these results we propose that in glioma C6 cells (and presumably in normal glia) peripheral benzodiazepine receptor interacts functionally with gamma-aminobutyric acid A type of receptor, which appears not to be linked to picrotoxin sensitive Cl- channel, and may be linked to phospholipase A2.

Animals↗
PubMed1987

Evidence implicating alpha-2 adrenergic receptors in the anticonvulsant action of intranigral muscimol.

The effects of systemically administered catecholamine receptor antagonists on the anticonvulsant action produced by local application of a gamma-aminobutyric acid agonist, muscimol, to the substantia nigra of rats were studied. Both electroshock and kindled seizures were studied. Two alpha-2 receptor antagonists, idazoxan and yohimbine, blocked the anticonvulsant action of intranigral muscimol in the electroshock model. Neither a beta nor an alpha-1 adrenergic nor a dopamine-2 receptor antagonist blocked this action. In contrast to electroshock seizures, an alpha-2 antagonist only partially reversed the anticonvulsant action of intranigral muscimol in the kindling model. We interpret the data to indicate that the interaction of norepinephrine with alpha-2 receptors is required for the anticonvulsant action of intranigral muscimol in the electroshock model. The only partial reversal found in the kindling model suggests that nigral control of seizure propagation involves more than alpha-2 receptor mediated neurotransmission.

Animals↗
PubMed1981

Effects of muscimol alone and in combination with diazepam on shuttle-box performance in rats.

Muscimol and diazepam reduced the number of avoidance responses of rats subjected to a conditioned avoidance situation. Diazepam, in a dose which per se did not influence the conditioned responses, significantly increased the disruption of avoidance behavior induced by muscimol. Bicuculline counteracted the avoidance impairment produced by muscimol, whereas it did not influence the disruption of avoidance performance induced by diazepam. Results are discussed with reference to the role of GABAergic system in the behavioral effects of muscimol and diazepam.

Animals↗