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 829 records · Page 46Linked to original sources
PubMed2003

Functional evidence for a role of GABA receptors in modulating nerve activities of circular smooth muscle from rat colon in vitro.

In the enteric nervous system, activation of neuronal GABA(A)- and GABA(B)-receptors has been shown to modulate neuronal activity. The consequences of this modulation depend on the location in the gastrointestinal tract or the animal species studied. These data illustrate the complexity of GABA-induced effects. Furthermore, the GABA(C)-receptor has been identified in a neuroendocrine cell line suggesting a modulating role of this third type of GABA receptor in intestinal functions. Therefore, the modulating role of GABA-receptor agonists was determined in circular preparations of rat distal colon during electrical nerve stimulation (NS) in vitro. Mechanical response to NS was characterized by a relaxation followed at the end of the stimulation by an off-contraction. In normal Krebs solution (basal conditions), muscimol and baclofen, respectively GABA(A)- and GABA(B)-agonists, induced a significant increase of the electrically induced off-contraction. The GABA(C) agonist, CACA, showed no significant effect on the response to NS. Excitatory effects of muscimol on the off-contraction were abolished in the presence of atropine. Furthermore, in the presence of atropine, muscimol increased the amplitude of the electrically induced relaxation; similarly the baclofen-induced increase of off-contraction amplitude was significantly lower than that observed in control conditions. Baclofen and muscimol effects on the off-contraction were abolished in the presence of hexamethonium or guanethidine. Furthermore, muscimol and baclofen did not induce any significant change on the response to NS in the presence of L-NAME and apamin together. Thus, it seems that in rat distal colon, GABA regulates significantly both excitatory (through GABA(A)- and GABA(B)-receptors) and inhibitory (through GABA(A)-receptors) neuronal activities. We also gave evidence for a possible interplay between GABAergic intrinsic neurons and adrenergic nerve terminals. Finally, it is shown for the first time the presence of the GABA vesicular transporter (VIAAT) around myenteric ganglia of rat colon.

Amino Acid Transport Systems↗
PubMed1996

Inhibition of GABAA receptor chloride channel by quinolones and norfloxacin-biphenylacetic acid hybrid compounds.

Receptor binding studies have shown that the combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, inhibits GABAA receptors. In order to elucidate further the mechanism of these drug interactions, the effect of quinolone antibacterial agents on muscimol-stimulated 36Cl- uptake in rat cerebral cortical synaptoneurosomes was investigated in the absence or presence of BPAA. In the absence of BPAA, quinolones such as norfloxacin (NFLX) and enoxacin attenuated muscimol-stimulated 36Cl- uptake at 10 microM and above. In combination with 10 microM BPAA, the inhibitory effect of these drugs was potentiated and there was a parallel shift of the inhibition curves to the left for these drugs. BPAA alone (1 and 10 microM) did not affect basal or muscimol-stimulated 36Cl- uptake. Hybrid molecules of NFLX and BPAA were synthesized and their inhibitory potency was also investigated. Inhibition curves of muscimol-stimulated 36Cl- uptake revealed that a hybrid with a -CONH(CH2)3- chain between NFLX and BPAA (flexible structure) (1 nM-20 microM) inhibited muscimol-stimulated 36Cl- uptake more potently than did the combination of NFLX (10 nm-100 microM) and 10 microM BPAA. In contrast, another hybrid linked by -CONH-(stretched structure) exhibited a weak inhibitory effect at 10 microM. These results suggest that quinolones in combination with BPAA bind to GABAA receptors, thus inhibiting Cl- channel activity, and that the inhibitory potency of quinolones may be enhanced by an intermolecular interaction with BPAA.

Animals↗
PubMed2000

Involvement of the medial precentral prefrontal cortex in memory consolidation for inhibitory avoidance learning in rats.

Adult male Wistar rats were trained in a step-down inhibitory avoidance learning task (3.0-s, 0.4-mA foot shock), received a 0.5-microl infusion of muscimol (0.02, 0.1, or 0.5 microg), AP5 (0.16, 0.34, 0. 5, 1.6, or 5.0 microg), SCH 23390 (0.05, 0.34, 0.5, or 1.75 microg), saline, or vehicle (DMSO 20%) into the anterior medial precentral area (Fr2) (CI) immediately after training, and were tested 24 h later. Muscimol (0.02, 0.1, or 0.5 microg), AP5 (0.34 or 0.5 microg), or SCH (0.5 or 1.75 microg) were amnesic. Then, animals were infused with muscimol (0.1 or 0.5 microg), AP5 (0.34, 0.5, or 5.0 microg), or SCH (0.5 microg) at other posttraining times and/or into the junction of Fr1-Fr2 (CII). Muscimol (0.1 and 0.5 microg) or SCH into CI were amnesic when given 90 or 180 min after training, but not when given 270 min after training. Muscimol (0.5 microg, but not 0.1 microg) or SCH into CII were amnesic when given 90 min after training, but not when given 0 or 180 min after training. AP5 (0.5, but not 5.0 microg) was amnesic when given into CI, but not into CII, at 0 or 180 min posttraining, and a trend toward an amnesic effect was seen at 90 min posttraining. The results suggest that 1) the glutamatergic, GABAergic, and dopaminergic systems in Fr2 are involved in the consolidation of memory for inhibitory avoidance learning, either directly or as parts of modulatory systems; and 2) timing of involvement of anterior Fr2 (CI) is different from that of posterior Fr2 (CII).

2-Amino-5-phosphonovalerate↗
PubMed1999

Neurosteroid modulation of the GABAA receptor in the developing guinea pig cerebral cortex.

Developmental changes in 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone; 5alpha-3alpha-P) potentiation of muscimol and benzodiazepine binding to the GABAA receptor were studied in the guinea pig cerebral cortex at three prenatal ages (gestational day (GD) 40, GD 50, GD 62), and three postnatal ages (postnatal day (PD) 11, PD 21, PD 61) (term, about GD 68). The number and affinity of [3H]flunitrazepam binding sites, and 5alpha-3alpha-P potentiation of [3H]muscimol and [3H]flunitrazepam binding to the GABAA receptor were determined at each age. There was no age effect on the affinity (Kd) for [3H]flunitrazepam. However, the number (Bmax) of [3H]flunitrazepam binding sites doubled between GD 40 and GD 62, and then declined slightly to reach adult levels by PD 11. 5alpha-3alpha-P produced a concentration-dependent potentiation of [3H]muscimol and [3H]flunitrazepam binding at each developmental age examined. The potency (high-affinity) for 5alpha-3alpha-P potentiation of both [3H]muscimol and [3H]flunitrazepam binding was lowest at GD 40, and increased to adult levels by GD 62. In contrast, the efficacy for 5alpha-3alpha-P potentiation of both [3H]muscimol and [3H]flunitrazepam binding was greatest at GD 40, and decreased to adult levels between GD 50 and GD 62. The percentage of high-affinity zolpidem binding sites increased in an age-dependent manner from 34.2+/-2.2% at GD 40, to reach adult levels by GD 62 (59. 4+/-2.5%). These data suggest that 5alpha-3alpha-P can modulate GABAA receptors in the immature cerebral cortex, and that changes in 5alpha-3alpha-P action are temporally related to changes in GABAA receptor benzodiazepine pharmacology late in gestation in the guinea pig.

Animals↗
PubMed2002

Effects of etifoxine on ligand binding to GABA(A) receptors in rodents.

The GABA(A) receptor/chloride ionophore is allosterically modulated by several classes of anxiolytic and anticonvulsant agents, including benzodiazepines, barbiturates and neurosteroids. Etifoxine, an anxiolytic and anticonvulsant compound competitively inhibited the binding of [(35)S]t-butylbicyclophosphoro-thionate (TBPS), a specific ligand of the GABA(A) receptor chloride channel site. To investigate the etifoxine modulatory effects on the different binding sites of the GABA(A) receptor complex, we have examined the effects of etifoxine on binding of the receptor agonist [(3)H]muscimol and the benzodiazepine modulator [(3)H]flunitrazepam in rat brain membrane preparations. The anticonvulsant properties of etifoxine combined with muscimol and flunitrazepam were performed in mice with picrotoxin-induced clonic seizures. Etifoxine modestly enhanced binding of [(3)H]muscimol and of [(3)H]flunitrazepam by increasing the number of binding sites without changing the binding affinity of [(3)H]flunitrazepam. In contrast, the compound decreased the affinity of muscimol for its binding site. In vivo, the combination of subactive doses of etifoxine with muscimol or flunitrazepam produced an anticonvulsant additive effect against the picrotoxin-induced clonic seizures in mice. These results suggest that the interaction of etifoxine on the GABA(A) receptor complex would allosterically modify different binding sites due to conformational changes. Functionally, the resulting facilitation of GABA transmission underlies the pharmacological properties of etifoxine.

Animals↗
PubMed2003

Normal coupling of brain benzodiazepine and neurosteroid modulatory sites on the GABA-A receptor complex in human hepatic encephalopathy.

To assess the possible implication of the allosteric coupling of different modulatory sites at the GABA-A receptor complex in hepatic encephalopathy (HE), we investigated in autopsied frontal cortex of six cirrhotic patients and six appropriately-matched controls, the modulatory effects of the benzodiazepine site agonist flunitrazepam on the binding of [3H]muscimol and the effect of the neurosteroid site agonist allopregnanolone (5alpha-pregnan-3alpha-ol-20-one) on the binding of [3H]muscimol and [3H]flunitrazepam. There were no significant differences in either the magnitude E(max): 11.5+/-1.1% (controls) versus 10.2+/-2.2% (HE patients) or the efficacy EC(50): 20.2+/-5.5 nM (controls) versus 17.7+/-6.2 nM (HE patients) of flunitrazepam modulation of [3H]muscimol binding. Allopregnanolone also showed modulation of both sites to a comparable extent in brain tissue from cirrhotic patients and controls E(max): [3H]muscimol, 15.1+/-2.8% (controls) versus 13.8+/-1.9% (HE patients); [3H]flunitrazepam, 17.9+/-2.3% (controls) versus 19.1+/-2.3% (HE patients), EC(50): [3H]muscimol, 386.5+/-25.8 nM (controls) versus 373.8+/-13.1 nM (HE patients); [3H]flunitrazepam, 49.8+/-22.9 nM (controls) versus 55.5+/-14.0 nM (HE patients). These findings demonstrate unequivocally that the GABA-A sites and their benzodiazepine and neurosteroid modulatory sites manifest normal allosteric coupling in brain in human HE. Therefore, if increased "GABAergic tone" is implicated in the pathophysiology of HE, this must be the consequence of increased brain concentrations of endogenous benzodiazepine and/or neurosteroid ligands for components of the GABA-A receptor complex rather than alterations of the receptor proteins themselves.

Adult↗
PubMed1999

Equilibrium binding characteristics of [3H]thiomuscimol.

The equilibrium binding characteristics of the tritiated GABAA agonist, 5-aminomethyl-3-isothiazolol (thiomuscimol) are described. Using the filtration technique to separate bound- from free-ligand, [3H]thiomuscimol was shown to bind to the GABA(A) receptor site(s) in a saturable manner with a Kd value of 28+/-6.0 nM and a Bmax value of 50+/-4.0 fmol/mg original tissue. In parallel binding experiments, the Kd and Bmax values for [3H]muscimol were determined to be 5.4+/-2.8 nM and 82+/-11 fmol/mg original tissue, respectively. In binding assays using the centrifugation technique, Kd and Bmax values for [3H]thiomuscimol were found to be 116+/-22 nM and 154 13 fmol/mg original tissue, respectively, whereas a Kd value of 16+/-1.8 nM and a Bmax value of 155+/-8.0 fmol/mg original tissue were determined for [3H]muscimol. In comparative inhibition studies using the GABA(A) antagonist SR 95531 and a series of specific GABAA agonists, the binding sites for [3H]thiomuscimol and [3H]muscimol were shown to exhibit similar pharmacological profiles. Autoradiographic studies disclosed similar regional distribution of [3H]thiomuscimol and [3H]muscimol binding sites in rat brain. Highest densities of binding sites were detected in cortex, hippocampus, and cerebellum, whereas low densities were measured in the midbrain structures of rat cortex. In conclusion, the equilibrium GABA(A) receptor binding characteristics of [3H]thiomuscimol are very similar to those of [3H]muscimol.

Animals↗
PubMed1998

Effects of GABAergic drugs on physostigmine-induced improvement in memory acquisition of passive avoidance learning in mice.

1. The effect of gamma-aminobutyric acid (GABA) receptor agonists and antagonists on acquisition of a step-down passive avoidance learning in mice was measured in the presence and absence of physostigmine. 2. Intraperitoneal injection of different doses of the anticholinesterase drug physostigmine (0.1-0.3 mg/kg) increased acquisition in mice dose dependently. The maximum response was obtained with 0.3 mg/kg of the drug. Higher doses of the drug impaired acquisition of the learned response. To show the effect of the GABAergic system on acquisition, GABAA receptor agonists and antagonists were challenged against 0.2 mg/kg of physostigmine. 3. Administration of the GABAA receptor agonist muscimol but not the GABAB receptor agonist baclofen decreased the acquisition of the learned task. However, the improvement induced by physostigmine (0.2 mg/kg) was decreased by both muscimol and baclofen. A combination of both agonists caused a higher inhibitory effect on the physostigmine response. 4. Pretreatment of animals with the higher doses of GABAA receptor antagonists bicuculline and picrotoxin but not the GABAB receptor antagonist phaclofen impaired learning. Both the GABAA and GABAB receptor antagonists reduced the learning improvement induced by physostigmine. The inhibitory effects of the GABAA and GABAB receptor antagonists are lost when combined together. 5. Bicuculline, picrotoxin or phaclofen increased the impairment of learning induced by muscimol, whereas a combination of either of the antagonists with baclofen did not alter the learning. The GABAA antagonists reduced the inhibitory effect of muscimol, whereas a higher dose of phaclofen increased the inhibition of the physostigmine response induced by muscimol and baclofen on physostigmine-induced learning improvement. 6. Phaclofen decreased but a higher dose of bicuculline increased the baclofen-induced inhibition of physostigmine effect. 7. It is concluded that both GABAA and GABAB activation inhibit improvement of acquisition induced by physostigmine.

Animals↗
PubMed1997

Involvement of pallidal and nigral GABA mechanisms in the generation of tremulous jaw movements in rats.

Four experiments were conducted to investigate the role of pallidal and nigral GABA in the generation of tremulous jaw movements in rats. In these experiments, tremulous jaw movements were induced by i.p. injections of the anticholinesterase tacrine (5.0 mg/kg). Previous work has shown that the tremulous jaw movements induced by cholinomimetics and dopamine depletion are dependent upon striatal mechanisms. Thus, the present study investigated potential striatal output pathways that could be involved in the generation of these movements. Because there are GABAergic projections from neostriatum to entopeduncular nucleus (medial globus pallidus) and substantia nigra pars reticulata, the GABA agonist muscimol was injected directly into these structures to study the effects of GABA stimulation on tacrine-induced jaw movements. Injections of muscimol into the entopeduncular nucleus (25-100 ng) failed to have any significant effects on tacrine-induced vacuous jaw movements. However, injections of muscimol (12.5-50 ng) into the substantia nigra pars reticulata blocked the jaw movements induced by tacrine. In the third experiment, it was again demonstrated that 25.0 ng of muscimol injected directly into the substantia nigra pars reticulata blocked the jaw movements induced by tacrine; in addition, it was shown that injections of this dose 2.0 mm dorsal to the substantia nigra pars reticulata failed to affect tacrine-induced tremulous jaw movements. It was shown in the fourth experiment that injections of muscimol into a more medial portion of the substantia nigra pars reticulata also reduced tacrine-induced tremulous jaw movements. These results indicate that stimulation of GABA(A) receptors in substantia nigra pars reticulata can block tacrine-induced tremulous jaw movements. This finding is consistent with the notion that striatonigral GABA projections are involved in the generation of tremulous jaw movements. It is also possible that striatonigral GABA mechanisms are involved in human clinical phenomena such as parkinsonian tremor.

Animals↗
PubMed2002

The interaction of morphine and gamma-aminobutyric acid (GABA)ergic systems in anxiolytic behavior: using mu-opioid receptor knockout mice.

We investigated the interaction of morphine and gamma-aminobutyric acid (GABA)ergic systems in anxiolytic action using mu-opioid receptor knockout and wild-type female mice. An elevated plus-maze test was used to assess anxiolytic behavior. The anxiolytic activities were monitored after experimental animals were pretreated with morphine [15 mg/kg, subcutaneous (s.c.)] and 3 h later received a single dose of muscimol (0.5 mg/kg, s.c.). In another experiment, mice received a single dose of opioid antagonist, naloxone [1.0 mg/kg, intraperitoneal (i.p.)], or GABA(A) receptor antagonist, (+)bicucullin (2.0 mg/kg, i.p.), 2.5 h after the morphine and 30 min before the muscimol injection. Control mice received vehicle only. The results show that morphine enhanced muscimol-induced staying time in open arms by 160% in wild-type mice. Moreover, the effect of morphine in the wild type was inhibited by the pretreatment of either naloxone or (+)bicucullin. Autoradiographic analysis indicated that morphine-administration raised [(3)H]muscimol binding by around 25% of the basal level in posterior thalamic, mediodorsal thalamic, and amygdaloid areas, but not in the hippocampal area in wild-type mice. In contrast, morphine administration did not alter the [(3)H]muscimol binding in mu-opioid receptor knockout mice. The present results reveal that mu-opioid receptor may play a role in the modification of anxiolytic behavior regulated by GABAergic neurotransmission.

Animals↗
PubMed2003

Comparison of the effects of allopregnanolone with direct GABAergic agonists on ethanol self-administration with and without concurrently available sucrose.

Behavioral effects of ethanol are mediated by actions at multiple neurotransmitter receptors and signaling systems; prominent among these is the type A gamma-aminobutyric acid (GABA(A)) receptor. Previous work has shown that the GABAergic neuroactive steroid allopregnanolone enhances ethanol-reinforced instrumental responding in rat. In the current study, we compared the effects of allopregnanolone with the direct GABA(A) agonist muscimol and the direct type B GABA (GABA(B)) agonist baclofen in male Long-Evans rats lever pressing for a 10% ethanol solution in a limited-access procedure. The effects of concurrently available sucrose were also tested to determine the selectivity of these drugs for altering ethanol self-administration when an alternate reinforcer was available. In Experiment 1, we found that presession systemic administration of both muscimol (0.3 and 1 mg/kg) and baclofen (1 and 3 mg/kg) reduced responding for ethanol. In contrast, allopregnanolone (3 and 5.6 mg/kg) enhanced responding for ethanol. In Experiment 2, we found that a 1-mg/kg dose of baclofen reduced responding for ethanol, but not for sucrose, whereas both baclofen and muscimol, administered at a higher dose of 3 mg/kg, decreased both ethanol- and sucrose-reinforced responding. Allopregnanolone, at a dose of 5.6 mg/kg, but not of 3 mg/kg, selectively increased ethanol-reinforced responding, indicating a less robust effect of allopregnanolone on responding within the concurrent reinforcement procedure than that observed when ethanol alone was available. The results support the suggestion that direct agonist action at either the GABA(A) or the GABA(B) receptor decreases ethanol self-administration. Muscimol produces a nonselective decrease in instrumental responding, whereas baclofen may selectively reduce ethanol intake at lower doses, but not higher ones, possibly limiting its potential use for treatment of alcohol abuse in human beings. In contrast, allopregnanolone can selectively enhance ethanol self-administration in the presence of a concurrently available alternate reinforcer, indicating that the direct GABA(A) agonist muscimol and the allosteric GABA(A) modulator allopregnanolone do not produce similar behavioral effects on instrumental responding for ethanol reinforcement.

Alcohol Drinking↗
PubMed2000

Activation of GABA receptors in the NTS of awake rats reduces the gain of baroreflex bradycardia.

In the present study we evaluated the effects of bilateral microinjection of muscimol (a GABA(A) receptor agonist) and baclofen (a GABA(B) receptor agonist) into the lateral commissural nucleus tractus solitarii (NTS) of awake rats on the gain of the baroreflex (BG) activated by a short duration (10-15 s) infusion of phenylephrine (Phe, 2.5 microg/0.05 ml, i.v.). Microinjection of muscimol (50 pmol/50 nl, n=8) into the NTS produced a significant increase in baseline mean arterial pressure ((MAP) 122+/-6 vs. 101+/-2 mmHg), no changes in baseline heart rate (HR) and a reduction in BG (-1.59+/-0. 1 vs. -0.69+/-0.1 beats/mmHg). Microinjection of baclofen (6.25 pmol/50 nl, n=6) into the NTS also produced a significant increase in baseline MAP (138+/-5 vs. 103+/-2 mmHg), no changes in baseline HR and a reduction in BG (-1.54+/-0.3 vs. -0.53+/-0.2 beats/mmHg). Considering that the reduction in BG could be secondary to the increase in MAP in response to microinjection of muscimol (n=6) or baclofen (n=7) into the NTS, in these two groups of rats we brought the MAP back to baseline by infusion of sodium nitroprusside (NP, 3.0 microg/0.05 ml, i.v.). Under these conditions, we verified that the BG remained significantly reduced after muscimol (-1.49+/-0.2 vs. -0.35+/-0.2 beats/mmHg) and after baclofen (-1.72+/-0.2 vs. -0.33+/-0.2 beats/mmHg) when compared to control. Reflex tachycardia was observed during the normalization of MAP by NP infusion and, in order to prevent the autonomic imbalance from affecting BG, we used another group of rats treated with atenolol (5 mg/kg, i.v.), a beta1 receptor antagonist. In rats previously treated with atenolol and submitted to NP infusion, we verified that BG remained reduced after microinjection of muscimol or baclofen into the NTS. The data show that activation of GABA(A) and GABA(B) receptors, independently of the changes in the baseline MAP or HR, inhibited the neurons of the NTS involved in the parasympathetic component of the baroreflex.

Animals↗
PubMed2006

GABA(A) receptor function is regulated by lipid bilayer elasticity.

Docosahexaenoic acid (DHA) and other polyunsaturated fatty acids (PUFAs) promote GABA(A) receptor [(3)H]-muscimol binding, and DHA increases the rate of GABA(A) receptor desensitization. Triton X-100, a structurally unrelated amphiphile, similarly promotes [(3)H]-muscimol binding. The mechanism(s) underlying these effects are poorly understood. DHA and Triton X-100, at concentrations that affect GABA(A) receptor function, increase the elasticity of lipid bilayers measured as decreased bilayer stiffness using gramicidin channels as molecular force transducers. We have previously shown that membrane protein function can be regulated by amphiphile-induced changes in bilayer elasticity and hypothesized that GABA(A) receptors could be similarly regulated. We therefore studied the effects of four structurally unrelated amphiphiles that decrease bilayer stiffness (Triton X-100, octyl-beta-glucoside, capsaicin, and DHA) on GABA(A) receptor function in mammalian cells. All the compounds promoted GABA(A) receptor [(3)H]-muscimol binding by increasing the binding capacity of high-affinity binding without affecting the associated equilibrium binding constant. A semiquantitative analysis found a similar quantitative relation between the effects on bilayer stiffness and [(3)H]-muscimol binding. Membrane cholesterol depletion, which also decreases bilayer stiffness, similarly promoted [(3)H]-muscimol binding. In whole-cell voltage-clamp experiments, Triton X-100, octyl-beta-glucoside, capsaicin, and DHA all reduced the peak amplitude of the GABA-induced currents and increased the rate of receptor desensitization. The effects of the amphiphiles did not correlate with the expected changes in monolayer spontaneous curvature. We conclude that GABA(A) receptor function is regulated by lipid bilayer elasticity. PUFAs may generally regulate membrane protein function by affecting the elasticity of the host lipid bilayer.

Animals↗
PubMed2001

GABA mechanisms and antinociception in mice with ligated sciatic nerve.

In the present study, the effects of GABA (gamma-aminobutyric acid) receptor agonists and antagonists on hyperalgesia induced by sciatic nerve ligation was investigated in mice. The response to morphine or GABA receptor agonists was examined 14 days after unilateral nerve ligation by hot-plate test. Intraperitoneal injection of different doses of morphine (3, 6 and 9 mg/kg), muscimol (0.5, 1 and 2 mg/kg) or baclofen (1, 2.5 and 5 mg/kg) induced a dose-related antinociception in both intact and ligated mice. The response of morphine but not that of muscimol or baclofen, in nerve-ligated mice was significantly less than that induced in the intact animals. The responses induced by muscimol or baclofen in nerve-ligated animals, were reduced by bicuculline or CGP35348 [P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid], respectively. However, morphine in combination with muscimol (2 mg/kg) tends to induce higher response; the combination of the GABA receptor agonists with morphine did not show potentiation, but additive effect. The opioid receptor antagonist naloxone reduced the response induced by muscimol in nerve-ligated animals. It was concluded that although ligation of the sciatic nerve clearly reduced the analgesic effect of morphine and not that of the GABA agonists, the results nevertheless indicated that morphine and the GABA(A) agonist shared the same mechanism of action.

Animals↗
PubMed1999

Feeding induced by GABA(A) receptor stimulation within the nucleus accumbens shell: regional mapping and characterization of macronutrient and taste preference.

This study investigated the areas of the nucleus accumbens shell involved in the modulation of feeding behavior by GABAergic stimulation and characterized this response using macronutrient diets as well as saline, sucrose, and saccharin solutions. The GABA agonist muscimol induced a pronounced feeding response when infused in the medial nucleus accumbens shell but not in the ventral or lateral accumbens shell. In the macronutrient preference study, muscimol increased the intake of both high fat and high carbohydrate diets when presented separately. When both diets were available simultaneously, muscimol stimulated feeding of both diets to the same degree. Muscimol elicited a robust increase in the consumption of sucrose solution. However, no effect of muscimol was demonstrated for water, saline, or saccharin intake. These findings provide evidence for a selective role for GABA-sensitive neurons in the medial accumbens shell in the regulation of ingestive behavior and further suggest that GABA(A) receptors in this region do not modulate palatability, macronutrient selection, or rewarding properties of food.

Animals↗
PubMed1987

GABA and benzodiazepine receptors in the gerbil brain after transient ischemia: demonstration by quantitative receptor autoradiography.

Quantitative receptor autoradiography was used to measure the binding of gamma-aminobutyric acid (GABA) and benzodiazepine receptors after ischemia by means of transient occlusion of bilateral common carotid arteries in the gerbil. [3H]Muscimol was used to label the GABAA receptors and [3H]flunitrazepam to label central type benzodiazepine receptors. In the superolateral convexities of the frontal cortices, [3H]muscimol binding was increased in 60% of the animals killed 3 days after ischemia, and decreased in 67% of the animals killed 27 days after ischemia. Twenty-seven days after ischemia, [3H]flunitrazepam binding in the substantia nigra pars reticulata increased to 252% of the control, though the increase in [3H]muscimol binding was not significant. In the dorsolateral region of the caudate putamen, marked neuronal necrosis and depletion of both [3H]muscimol and [3H]flunitrazepam binding sites were observed 27 days after ischemia, the ventromedial region being left intact. In spite of the depletion of pyramidal cells in the CA1 region of the hippocampus, both [3H]muscimol and [3H]flunitrazepam binding sites were preserved 27 days after ischemia. Since our previous study revealed that adenosine A1 binding sites were depleted in the CA1 subfield of the hippocampus after ischemia correlating with neuronal damage, GABAA and benzodiazepine receptors may not be distributed predominantly on the pyramidal cells in the CA1 region.

Animals↗
PubMed2006

Limbic system participates in mediating the effects of general anesthetics.

In a previous study, we reported that inactivation of the medial septum or the hippocampus by muscimol, a GABA(A) receptor agonist, potentiated the effects of a general anesthetic. In this study, we further investigated whether other structures that are connected to the septohippocampal system are involved in mediating general anesthesia. In freely behaving rats, muscimol (0.25 microg) or saline was infused intracerebrally into one of four areas-the supramammillary area (SUM), nucleus accumbens (NAC), ventral pallidum (VP), and ventral tegmental area (VTA)-and righting, pain, and EEG responses were recorded following either halothane or sodium pentobarbital, representing inhalational and injectable general anesthetic, respectively. The effect of halothane (2%) or pentobarbital (20 mg/kg i.p.) in abolishing the righting, pain response, or low-voltage neocortical activity was enhanced, and the initial behavioral hyperactivity (delirium) was reduced, after muscimol as compared to after saline infusion in SUM, NAC, VP, and VTA. EEGs in the hippocampus and the sensorimotor cortex following halothane or pentobarbital showed increased delta, and decreased hippocampal theta and gamma waves after muscimol infusion as compared to saline infusion in SUM, NAC, VP, and VTA. By contrast, infusion of muscimol in the median raphe increased locomotion and did not significantly alter the behavioral or EEG effects of halothane or pentobarbital. It is suggested that structures that activate the limbic cortices (MS, SUM, and VTA but not the median raphe) or mediate the output of the hippocampus (NAC and VP) normally participate in maintaining consciousness and inactivation of these structures potentiates the response to a general anesthetic.

Anesthetics↗
PubMed2002

Reduction of drug-induced yawning and penile erection and of noncontact erections in male rats by the activation of GABAA receptors in the paraventricular nucleus: involvement of nitric oxide.

The effect of muscimol, a GABAA receptor agonist, injected into the paraventricular nucleus (PVN) of the hypothalamus on drug-induced (apomorphine, oxytocin and NMDA) yawning and penile erection, and on the increase in the concentration of NO2- and NO3- occurring in the paraventricular dialysate in these experimental conditions, was studied in male rats. Muscimol (50, 100 and 200 ng) reduced, in a dose-dependent manner, penile erection and yawning induced by apomorphine (50 ng), oxytocin (30 ng) and NMDA (50 ng) delivered into the PVN. The reduction of penile erection and yawning was parallel to a reduction of the concomitant NO2- and NO3- increase that occurs in the paraventricular dialysate in this experimental condition. In contrast, baclofen (200 ng), a GABAB receptor agonist, was ineffective. The muscimol effects on drug-induced penile erection, yawning and NO2- increase were prevented by the prior administration of bicuculline (250 ng into the paraventricular nucleus). Muscimol (200 ng) but not baclofen (200 ng), injected into the PVN, reduced both noncontact erections in male rats placed in the presence of an inaccessible receptive female, and also the NO2- increase that occurs in the paraventricular dialysate in this experimental condition. As found with drug-induced penile erection, the muscimol reduction of noncontact erections and of NO2- increase was prevented by bicuculline. The present results show that the activation of GABAA receptors in the PVN reduces yawning and penile erection induced by drugs or physiological stimuli by reducing the increase in NO activity that occurs in this hypothalamic nucleus in these experimental conditions.

Animals↗