Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Muscimol”

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

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

At least 127 records · Page 7Linked to original sources
PubMed2003

Neonatal cholinergic lesions and development of exploration upon administration of the GABAa receptor agonist muscimol in preweaning rats.

Neonatal rats were administered 192 IgG-saporin (192 IgG-Sap), a selective cholinergic immunotoxin, on postnatal day (PND) 7. Behavioural responsiveness to muscimol, a GABAa receptor agonist, was then assessed using locomotor activity and object exploration tests on PND 18. In Experiment 1, 192 IgG-Sap-lesioned and control rats were injected with the GABAa agonist, muscimol, on PND 18 and tested in a standard open field test. Muscimol reduced rearing responses in both control and 192 IgG-Sap-lesioned animals whereas reduced wall-rearing responses occurred in control animals only. 192 IgG-Sap also reduced rearing and wall-rearing responses. In Experiment 2, muscimol effects were evaluated on PND 18 in a spatial open field test in which object exploration in addition to locomotion and rearing responses was assessed. Neonatal cholinergic lesion per se increased locomotion during object exploration while decreasing time spent exploring objects. Depressant effects of muscimol on object exploration were also evident. As a whole, these data provide evidence for (i) basal forebrain (BF) cholinergic control on locomotor activity and object exploration and (ii) GABAa-mediated regulation of selective behavioural patterns associated with locomotion and exploration in weaning rats. Neonatal cholinergic lesions, however, do not appear to alter reactivity to GABAergic agonists in juvenile rats.

Animals↗
PubMed1998

Regional differences within the rat ventral tegmental area for muscimol self-infusions.

The present study examined the effects of activating GABA(A) receptors in the anterior and posterior regions of the ventral tegmental area (VTA) on operant reinforcement behavior, using the technique of intracranial self-administration. Rats were given the opportunity to self-administer vehicle alone (artificial CSF) and vehicle containing 25, 50, and 100 microM muscimol, a GABA(A) agonist, into the anterior or posterior VTA during four sessions (3 h/session) in standard two-lever operant chambers. Rats received five times greater infusions of 50 and 100 microM muscimol than vehicle into the posterior VTA; both doses significantly increased responding above vehicle levels on the active and inactive (control) levers equally. When the response requirement for muscimol infusions was increased from a fixed-ratio 1 (FR1) to FR3 in a single-lever chamber, the total session responses increased approximately twofold. Muscimol was not self-infused when cannula placements were in the anterior VTA. The self-infusion of muscimol into the posterior VTA was attenuated by coadministration of picrotoxin. Overall, the results suggest that the activation of GABA(A) receptors in the posterior VTA produces goal-directed behavior.

Animals↗
PubMed1989

Intraseptal administration of muscimol produces dose-dependent memory impairments in the rat.

The present study examined the effects of intraseptal administration of the GABAergic agonist muscimol on performance of a radial-arm maze (RAM) task. Male Long-Evans rats were trained to perform a RAM task in which a 1-h delay was imposed between the sample and the test session. In this task rats have access to four out of eight maze arms during a predelay session. Following a 1-h delay, rats are returned to the maze and allowed to freely choose among all eight arms. Arms not blocked during the predelay session are baited, and entry into an arm chosen during the predelay session or a repeated entry into a postdelay chosen arm constitutes an error. Following acquisition, animals were implanted with a single cannula aimed at the medial septum. A within-subjects design was utilized to examine the effects of intraseptal administration of muscimol (0.0, 0.75, 1.5 or 3.0 nmol) on performance in this task. All drugs or artificial cerebrospinal fluid were administered immediately following the predelay session. Muscimol, a GABA-A agonist, produced a dose-dependent impairment in maze performance as evidenced by fewer correct choices in the first four postdelay choices and an increase in the number of errors. Intraseptal administration of muscimol did not significantly alter latency per choice on the RAM task nor did it affect locomotor activity levels. Muscimol-induced impairments were also observed when a 4-h delay was imposed between the fourth and the fifth maze selection, suggesting that the behavioral deficit represents an inability to store or retain spatial working memories rather than a general performance deficit. These data indicated that pharmacological manipulation of GABA-A receptors within the medial septum modifies working memory processes. The potential interaction of GABAergic and cholinergic mechanisms in the modulation of working memory processes is discussed.

Animals↗
PubMed1999

Prevention of muscimol-induced long-term depression by brain-derived neurotrophic factor.

1. The authors have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal slices. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone. It was also shown that glutamate receptor activity is not involved in the induction of this novel type of long-term depression. Brain derived neurotrophic factor is a member of the neurotrophins family widely expressed in the central nervous system. There is increasing evidence that indicate an important role for brain-derived neurotrophic factor in synaptic plasticity. It has been reported that brain-derived neurotrophic factor level is downregulated by GABA system. The present study investigated a possible relation between muscimol-induced long-term depression and brain-derived neurotrophic factor level. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibers in stratum radiatum. 3. It was observed that brain-derived neurotrophic factor at concentration that did not have any effect itself on the population spike, prevents the induction of long-term depression by muscimol. In addition to this, K-252a an inhibitor of Trk type kinase blocked the prevention of muscimol-induced LTD by brain-derived neurotrophic factor. 4. The results suggest that there is an interaction between muscimol-induced long-term depression and brain-derived neurotrophic factor and may explain the post receptor mechanism of muscimol-induced long-term depression through a bilateral relation between GABAA activity and brain-derived neurotrophic factor.

Animals↗
PubMed2003

Enhancing and inhibitory effects of H2-receptor antagonists on the GABA and the GABAA-agonist muscimol responses of the isolated guinea pig ileum: a pharmacodynamic interaction.

This study investigates the effect of histamine H(2)-receptor antagonists on the GABA-responses of the intestine. GABA and the GABA(A)-agonist muscimol were applied to isolated ileal guinea pig preparations in the absence, and presence of two H(2)-receptor antagonists, famotidine and cimetidine. Both GABA and muscimol produced a concentration-dependent contractile effect on the guinea pig ileum. Famotidine and cimetidine modified this contractile effect, either by enhancing or by inhibiting it. The differing results depended not only on the antagonist concentration, but also on the concentration of GABA or muscimol. When tested at the concentration of 10(-5)M, famotidine enhanced the contractile response of the ileum to either GABA or muscimol, while cimetidine did not modify it. At the concentration of 3 x 10(-4)M, both H(2)-receptor antagonists tested inhibited the contractile effect of either GABA or muscimol. However, the famotidine-induced inhibition was more potent than the one produced by cimetidine. In conclusion, the interaction of H(2)-receptor antagonists with GABA receptors is not limited to the central nervous system, but it also extends to the peripheral nervous system. The receptor interaction mainly involves GABA(A)-receptors and depends on both the specific H(2)-antagonist and the concentration used.

Animals↗
PubMed1989

Kinetics of [3H]muscimol binding to the GABAA receptor in bovine brain membranes.

The binding of the GABA receptor agonist [3H]muscimol to membrane preparations from bovine cerebral cortex has been investigated in equilibrium and kinetic experiments. Equilibrium binding curves are biphasic and suggest that [3H]muscimol binds to both high-affinity (Kd approximately 10 nM) and low-affinity (Kd approximately 0.5 microM) sites. Binding to each class of sites is inhibited by GABA and by the specific GABAA receptor antagonist bicuculline. The kinetics of [3H]muscimol binding have been measured by using both manual filtration assays and an automated rapid filtration technique which permits the measurement of ligand dissociation on subsecond time scales. Association and dissociation curves are biphasic at all concentrations of [3H]muscimol studied, even under conditions of low receptor saturation when no significant occupancy of the low-affinity sites would be expected. These results cannot be simply explained by the presence of two populations of binding sites in the membrane preparations but suggest the existence of two forms of the monoliganded receptor. Dissociation constants for these two forms have been estimated to be 16 and 82 nM at 23 degrees C. At higher ligand concentrations, kinetic measurements have suggested that the binding of [3H]muscimol to low-affinity sites is accompanied by a slow conformational change of the receptor-ligand complex.

Animals↗
PubMed1997

Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli.

The GABAa agonist, muscimol (0.5 microgram in 0.5 microliter saline), or vehicle was infused into the lateral and basal amygdala nuclei prior to fear conditioning or testing in rats. Rats given muscimol before conditioning and saline before testing showed much less freezing to the conditioned stimulus (CS) and the context than did controls given saline before training and testing. Rats given saline before training and muscimol prior to testing also showed low levels of freezing to the CS and the context. In follow-up procedures, rats with acquisition initially blocked by pretraining muscimol infusions froze in a manner similar to that of controls when retrained and retested with saline infusions. Rats trained with saline but tested with muscimol presumably became conditioned but could express the learning. When retested with saline, they froze in the same manner as controls. Thus, activity in the lateral and basal amygdala appears to play an essential role in the acquisition and expression of fear conditioning.

Amygdala↗
PubMedDate not supplied

Intrahippocampal muscimol shifts learning strategy in gonadally intact young adult female rats.

Learning strategy preferences depend upon circulating estrogen levels, with enhanced hippocampus-sensitive place learning coinciding with elevated estrogen levels. The effects of estrogen on strategy may be mediated by fluctuations in GABAergic function, given that inhibitory tone in the hippocampus is low when estrogen is high. We investigated the effects on learning strategy of intrahippocampal injections of a GABA(A) agonist in gonadally intact female rats. On the day of training, rats received 0.3 microL intrahippocampal infusions of muscimol (0.26 nmol or 2.6 nmol) or saline 20 min prior to training on a T-maze in which place (hippocampus-sensitive) or response (striatum-sensitive) strategies offer effective solutions. Muscimol treatment increased the use of the response strategy in a dose-dependent manner without influencing learning speed, indicating that muscimol modulated strategy and not learning ability. Furthermore, the muscimol-related shift to response strategies varied across the estrous cycle. The results indicate that increasing inhibition in the hippocampus biases rats away from hippocampus-sensitive place learning strategies and toward hippocampus-insensitive response learning strategies without a learning deficit. Furthermore, rats at proestrus demonstrated the most dramatic shift in learning strategy following muscimol treatment compared with control conditions, while rats at estrus demonstrated the most complete bias toward response strategies. The enhanced use of hippocampus-sensitive strategies at proestrus likely results from reduced hippocampal inhibition.

Animals↗
PubMed1982

High specific binding of [3H]GABA and [3H]muscimol to membranes from dendrodendritic synaptosomes of the rat olfactory bulb.

Olfactory bulbs contain dendrodendritic synapses, which occur between granule cells and mitral cells, and gamma-aminobutyric acid (GABA) is thought to act as an inhibitory neurotransmitter at these synapses. Synaptosomes derived from the dendrodendritic synapses of the olfactory bulb were shown previously to contain considerable L-glutamate decarboxylase activity. The subcellular distribution and binding parameters of [3H]GABA and [3H]muscimol binding sites have now been determined in the rat olfactory bulb. Of all fractions examined, crude synaptic membranes (CSM) prepared from the dendrodendritic synaptosomes were shown to have the highest specific binding activity and accounted for nearly all of the total binding activity for both ligands. The specific binding activities for [3H]GABA and for [3H]muscimol were greatly increased after treating the CSM with 0.05% Triton X-100. Binding was shown to be Na+-independent, reversible, pharmacologically specific, and saturable. High- and low-affinity sites were detected for both ligands, and both classes of sites had appreciably lower KD values for muscimol (KD1 = 3.1 nM, KD2 = 25.1 nM) than for GABA (KD1 = 8.6 nM; KD2 = 63.7 nM). The amounts of the high-affinity binding sites for muscimol and GABA were similar (Bmax = 1.7 and 1.5 pmol/mg protein, respectively). The results of the present experiments indicate that the GABA and muscimol binding sites represent the GABA postsynaptic receptor, presumably on mitral cell dendrites, and provide further support for the hypothesis that GABA functions as a neurotransmitter at the dendrodendritic synapses in the olfactory bulb.

Animals↗
PubMed1983

Reaction of muscimol with 4-aminobutyrate aminotransferase.

The reaction of muscimol as amino donor substrate for GABA transaminase (GABA-T) has been studied using enzyme purified from rabbit brain. Enzyme activity was assayed by measuring the glutamate produced using glutamate dehydrogenase. Kinetic parameters determined at 37 degrees C were for GABA, Km (app) = 1.92 +/- 0.24 mM, specific activity = 7.33 +/- 0.27 mumol/min/mg (kcat = 13.7s-1), and for muscimol, Km (app) = 1.27 +/- 0.15 mM, specific activity = 0.101 +/- 0.009 mumol/min/mg (kcat = 0.19s-1). Addition of muscimol to the enzyme caused the spectral changes associated with conversion of the pyridoxaldimine form to the pyridoxamine form, and the first-order rate constant for the reaction showed a dependence on muscimol concentration that followed saturation kinetics, with a K = 1.1 +/- 0.18 mM and kmax = 0.065 +/- 0.004 s-1 (19 degrees C). The rate of spectral change observed on addition of muscimol to ornithine transaminase was extremely slow--at least an order of magnitude slower than that seen with GABA-T.

4-Aminobutyrate Transaminase↗
PubMed1983

Modulation of [3H]muscimol binding in rat cerebellar and cerebral cortical membranes by picrotoxin, pentobarbitone, and etomidate.

Modulation of [3H]muscimol binding by picrotoxin, pentobarbitone, and etomidate was investigated in rat cerebellar and cerebral cortical membranes. In cerebellum, at 37 degrees C in the presence of chloride ions (150 mM), picrotoxin and picrotoxinin decreased specific [3H]muscimol binding to 43 +/- 3% of control, with an EC50 of 1.2 +/- 0.1 microM. [3H]Muscimol saturation experiments in the presence and absence of picrotoxin indicated that the picrotoxin effect was primarily due to a loss of high-affinity muscimol sites with KD approximately equal to 10 nM. Pentobarbitone enhanced specific [3H]muscimol binding to 259 +/- 3% of control, with EC50 = 292 +/- 37 microM, and etomidate increased binding to 298 +/- 18%, with EC50 = 7.1 +/- 1.0 microM. The influence of temperature and chloride ion concentration on these effects was investigated by comparing experiments at 37 and 0 degrees C in the presence or absence of chloride at constant ionic strength. The results indicate that studies at 0 degrees C underestimate the coupling between GABA receptors and barbiturate sites and that they greatly overestimate the importance of chloride ions in this phenomenon. In cerebral cortical membranes (37 degrees C, 150 mM Cl-), the effect of picrotoxin was similar to that observed in cerebellum, whereas the effects of pentobarbitone and etomidate were greater, but occurred at higher concentrations.

Animals↗
PubMed1997

Role of paraventricular and dorsomedial nuclei of the hypothalamus and central nucleus of the amygdala on muscimol-induced cardiovascular responses.

Gamma-aminobutyric acid (GABA) plays an important role in the central control of cardiovascular functions. Previous evidence indicates that a tonically active GABAergic system exists in forebrain structures. The purpose of this study was to examine the role of the unilateral lesion of the central nucleus of amygdala, paraventricular or dorsomedial nuclei of the hypothalamus on muscimol-induced cardiovascular responses. Electrolytic ablation of nuclei was made by a monopolar isolated electrode under a stereotaxic instrument, 3-5 days before the experiments. Effects of intracerebroventricular injections of muscimol were investigated in intact, lesioned and sham-lesioned rats. On the day of the experiments, blood pressure and heart rate recordings were carried out in male Sprague-Dawley conscious rats. Muscimol produced decreases in arterial blood pressure and heart rate. The hypotensive effect of muscimol was completely inhibited in rats with dorsomedial nucleus lesions, whereas the bradycardic effect was partially prevented. The results indicate that the dorsomedial nucleus of the hypothalamus plays an important role on muscimol-induced blood pressure and heart rate responses.

Amygdala↗
PubMed1991

Age-dependent changes in cardiovascular responses induced by muscimol infused into the nucleus tractus solitarii and nucleus parabrachialis medialis in rats.

1. The effects of muscimol and bicuculline on mean arterial blood pressure (MAP) and heart rate (HR) were studied after their microinfusion into the nucleus tractus solitarii (NTS) and into the nucleus parabrachialis medialis (NPBmed) in 3 and 24 month old rats. 2. In 3 month old rats a dose of 0.01 microgram of muscimol given into the NTS increased MAP, whereas higher doses (0.05, 0.1 and 0.25 microgram) produced dose-dependent bradycardia with either no change (0.05 and 0.1 microgram) or a decrease (0.25 microgram) in MAP. 3. On the other hand, in 24 month old rats, the same doses of muscimol given into the NTS failed to change MAP, whereas in comparison to 3 month old rats they produced a significantly lesser bradycardia. 4. The cardiovascular changes elicited by infusion of muscimol into the NTS in 3 and 24 month old rats were prevented by prior microinfusion of bicuculline into the same site. 5. Muscimol given into the NPBmed in doses from 0.05 to 0.25 microgram produced, in 3 month old rats dose-dependent decreases in MAP and HR which were prevented by prior administration of bicuculline. These effects were significantly reduced in 24 month old rats. 6. The present experiments show that with aging there is impairment of GABA-ergic mechanisms involved in the regulation of cardiovascular activity in the NTS and NPBmed.

Aging↗
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↗
PubMed1981

Effect of ethanol and ethanol withdrawal on 3H-muscimol binding and behaviour in the rat: a pilot study.

Effect of acute and chronic exposure to and withdrawal from ethanol on 3H-muscimol binding in the forebrains and cerebelli and on withdrawal behaviour was investigated in 30 rats. Chronic exposure to and withdrawal from ethanol produced a significant reduction in the number of muscimol binding sites in the cerebelli. A negative correlation was observed between the number of muscimol binding sites in the forebrain and cerebellum in the chronic ethanol and withdrawal groups. Relatively high correlations were found between the number of muscimol binding sites and audiogenic seizures scores during withdrawal from ethanol. Since impaired GABAergic function is associated with increased susceptibility to seizures, there may be a casual relationship between the observed changes in muscimol binding and ethanol-induced audiogenic withdrawal seizures.

Animals↗
PubMed2001

Dorsal horn administration of muscimol abolishes the muscle pressor reflex.

The purpose of this study was to determine the effect of blocking synaptic transmission in the dorsal horn on the cardiovascular responses produced by activation of muscle afferent neurons. Synaptic transmission was blocked by applying the GABA(A) agonist muscimol to the dorsal surface of the spinal cord. Cats were anesthetized with alpha-chloralose and urethane, and a laminectomy was performed. With the exception of the L(7) dorsal root, the dorsal and ventral roots from L(5) to S(2) were sectioned on one side, and static contraction of the ipsilateral triceps surae muscle was evoked by electrically stimulating the peripheral ends of the L(7) and S(1) ventral roots. The dorsal surface of the L(4)--S(3) segments of the spinal cord were enclosed within a "well" created by applying layers of vinyl polysiloxane. Administration of a 1 mM solution of muscimol (based on dose-response data) into this well abolished the reflex pressor response to contraction (change in mean arterial blood pressure before was 47 +/- 7 mmHg and after muscimol was 3 +/- 2 mmHg). Muscle stretch increased mean arterial blood pressure by 30 +/- 8 mmHg before muscimol, but after drug application stretch increased MAP by only 3 +/- 2 mmHg. Limiting muscimol to the L(7) segment attenuated the pressor responses to contraction (37 +/- 7 to 24 +/- 11 mmHg) and stretch (28 +/- 2 to 16 +/- 8 mmHg). These data suggest that the dorsal horn of the spinal cord contains an obligatory synapse for the pressor reflex. Furthermore, these data support the hypothesis that branches of primary afferent neurons, not intraspinal pathways, are responsible for the multisegmental integration of the pressor reflex.

Afferent Pathways↗
PubMed1985

Modification of saccadic eye movements by GABA-related substances. II. Effects of muscimol in monkey substantia nigra pars reticulata.

The preceding study (21) showed that a gamma-aminobutyric acid (GABA) agonist or antagonist injected into the superior colliculus (SC) disrupted saccadic eye movements. The purpose of the present experiments was to determine whether this result was due to altering the inhibitory input to the SC from the substantia nigra pars reticulata (SNr). SNr cells are themselves inhibited by GABA. Injection of muscimol, a GABA agonist, into the SNr should increase the inhibition acting on SNr cells and should reduce the inhibition acting on the SC. If the effects of GABA inhibition in the SC results from terminals originating in the SNr, muscimol in the SNr should act like bicuculline in the SC. Muscimol in the SNr has the same general effect as bicuculline in the SC. The monkey made irrepressible saccades toward the contralateral visual field where cells in the SNr at the injection site had their visual or movement field. During visual fixation saccadic jerks occurred, interspersed with spontaneous saccades, instead of saccades to visual targets or to remembered targets. Saccades to remembered targets were more vulnerable to these saccadic intrusions than were saccades to visual targets. Since muscimol in the SNr acts like bicuculline in the SC, we conclude that a substantial fraction of GABA-mediated inhibitory inputs in the SC originates from the SNr. These experiments, in conjunction with previous experiments, show that the SNr exerts a tonic inhibition on saccade-related cells in SC and that this inhibition is mediated by GABA. The role of the SNr in initiation of saccades to remembered targets is particularly important since these saccades are more severely disrupted by muscimol in the SNr as well as in the SC. We suggest that both of these conclusions about eye movement might apply to skeletal movements as well. First, the basal ganglia contribute to the initiation of movement by a release of the target structure from tonic inhibition. Second, this mechanism is particularly critical of the movements based on stored or remembered signals that are not currently available as incoming sensory inputs.

Animals↗
PubMed1994

Differential effects of muscimol microinjection into dorsal and ventral aspects of the premotor cortex of monkeys.

1. A gamma aminobutyric acid (GABAA) receptor agonist, muscimol (Sigma, 5 micrograms/microliters solution), and a GABAB receptor agonist and antagonist, baclofen and phaclofen, respectively, were injected (1.0 microliter) into the dorsal and ventral aspects of the premotor cortex (PM) of two Japanese monkeys (Macaca fuscata), while they were performing a motor task that required wrist flexion or extension to a target. The correct movement was instructed by either 1) a conditional color cue [green or red light emitting diodes (LED)] equidistant from the targets or 2) a directional cue toward extension or flexion (right or left LED). When the green or right LED was illuminated, extension was to be performed. When the red or left LED was illuminated, flexion was required. The movement was triggered by a visual stimulus either simultaneously with the instruction stimulus or after a variable delay. 2. Before drug injection, single-unit recordings were made to select injection sites 1) in the dorsal aspect of the PM (PMd) around the superior precentral sulcus where typical set-related activity was frequently recorded and 2) in the ventral aspect of the PM (PMv) immediately caudal to the genu of the arcuate sulcus where movement-related neurons were densely located. 3. Behavioral deficits were observed primarily at the time muscimol, but not baclofen or phaclofen, was injected. Furthermore, muscimol effects were short-lasting: deficits were most frequently observed during the 10-min injection period but seldom after completion of injection. 4. When muscimol was injected into the PMd, there was an increase in the number of direction errors primarily when the conditional cues were presented. The initiated movements were similar in amplitude and velocity to the preinjection behavior. In contrast, when muscimol was injected into the PMv, many of the initiated movements showed smaller amplitudes and slower velocities, but few direction errors were made. 5. These results suggest that the PMd and PMv play differential roles in motor control: the PMd is more important than PMv in conditional motor behavior and plays a role in the preparation for forthcoming movements. In contrast, the PMv is more specialized for a role in the execution of visually guided movements.

Animals↗