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 883 records · Page 49Linked to original sources
PubMed1993

A new highly sensitive procedure--a prerequisite to evaluate the density of GABAA receptors and to study their allosteric properties in distinct areas of rat brain.

A new procedure for tissue preparation is described for the study of modulatory effects of neuroactive steroids and barbiturates on the in vitro binding of [3H]muscimol in distinct areas of rat brain. This method had been optimized for the highest amount of [3H]muscimol binding and a maximal effect of pentobarbital on radioligand binding. The following steps like tissue freezing, initial homogenization in alkaline triethanolamine buffer (pH 9.0), fractionated centrifugations and washings of the resulting membrane fractions in disodium piperazine-N-N'-bis[2-hydroxypropanesulfonic acid] buffer (pH 7.4) provided the best results. In spite of a shorter time of preparation compared to preparative techniques traditionally used our procedure yields GABAA receptor sites with a higher sensitivity to the binding of muscimol without affecting their allosteric properties thereby allowing the use of minute brain tissue samples as little as 50mg wet weight. The GABAA receptor sites of the resulting membrane fractions are viable as muscimol binding had a higher affinity in cerebellum (CER) (KD = 6.9 +/- 1nM) than frontal cortex (FC) (KD = 18.4 +/- 1.4nM) which is in the range of highly purified receptors; CER was significantly more densely labelled than FC; the IC50 value of 2 x 10(-7) M for bicucullin-methiodide and the magnitude of the effect of pentobarbital are similar to published results. The rapid modulatory onset of the action of 3-alpha-hydroxy-5-alpha-pregnane-20-one (HPO) which was effective after a preincubation of only 30s as well as the threshold concentration of 10nM HPO for enhancement of the binding of muscimol provided evidence for the high sensitivity of GABAA receptors to neuroactive steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Allosteric Regulation↗
PubMed2004

Role of cerebellar interpositus nucleus in the genesis and control of reflex and conditioned eyelid responses.

The role of cerebellar circuits in the acquisition of new motor abilities is still a matter of intensive debate. To establish the contribution of posterior interpositus nucleus (PIN) to the performance and/or acquisition of reflex and classically conditioned responses (CRs) of the eyelid, the effects of microstimulation and/or pharmacological inhibition by muscimol of the nucleus were investigated in conscious cats. Microstimulation of the PIN in naive animals evoked ramp-like eyelid responses with a wavy appearance, without producing any noticeable plastic functional change in the cerebellar and brainstem circuits involved. Muscimol microinjections decreased the amplitude of reflex eyeblinks evoked by air puffs, both when presented alone or when paired with a tone as conditioned stimulus (CS). In half-conditioned animals, muscimol injections also decreased the amplitude and damped the typical wavy profile of CRs, whereas microstimulation of the same sites increased both parameters. However, neither muscimol injections nor microstimulation modified the expected percentage of CRs, suggesting a major role of the PIN in the performance of eyelid responses rather than in the learning process. Moreover, the simultaneous presentation of CS and microstimulation in well trained animals evoked CRs similar in amplitude to the added value of those evoked by the two stimuli presented separately. In contrast, muscimol-injected animals developed CRs to paired CS and microstimulation presentations, larger than those evoked by the two stimuli when presented alone. It is concluded that the PIN contributes to the enhancement of both reflex and conditioned eyelid responses and to the damping of resonant properties of neuromuscular elements controlling eyelid kinematics.

Animals↗
PubMed2005

The inactivation of the basolateral nucleus of the rat amygdala has an anxiolytic effect in the elevated T-maze and light/dark transition tests.

Pharmacological evidence indicates that the basolateral nucleus of the amygdala (BLA) is involved in the mediation of inhibitory avoidance but not of escape behavior in the elevated T-maze test. These defensive responses have been associated with generalized anxiety disorder (GAD) and panic disorder, respectively. In the present study, we determined whether the BLA plays a differential role in the control of inhibitory avoidance and escape responses in the elevated T-maze. Male Wistar rats (250-280 g, N = 9-10 in each treatment group) were pre-exposed to one of the open arms of the maze for 30 min and 24 h later tested in the model after inactivation of the BLA by a local injection of the GABA A receptor agonist muscimol (8 nmol in 0.2 microL). It has been shown that a prior forced exposure to one of the open arms of the maze, by shortening latencies to withdrawal from the open arm during the test, improves the escape task as a behavioral index of panic. The effects of muscimol in the elevated T-maze were compared to those caused by this GABA agonist in the avoidance reaction generated in the light/dark transition test. This defensive behavior has also been associated with GAD. In the elevated T-maze, intra-BLA injection of muscimol impaired inhibitory avoidance (control: 187.70 +/- 14.90 s, muscimol: 37.10 +/- 2.63 s), indicating an anxiolytic effect, without interfering with escape performance. The drug also showed an anxiolytic effect in the light/dark transition test as indicated by the increase in the time spent in the lighted compartment (control: 23.50 +/- 2.45 s, muscimol: 47.30 +/- 4.48 s). The present findings point to involvement of the BLA in the modulation of defensive responses that have been associated with GAD.

Amygdala↗
PubMedDate not supplied

The role of GABA-ergic signal in the regulation of melatonin biosynthesis in vertebrate retina.

The in vivo effects of GABA-ergic drugs on the activity of serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), two enzymes involved in melatonin biosynthesis, were investigated in light-exposed chicken retina. The ip administration of muscimol and baclofen (direct agonists of GABA-A and GABA-B receptors, respectively), aminooxyacetic acid (an inhibitor of GABA transaminase), and nipecotic acid (an inhibitor of GABA reuptake), significantly increased the retinal NAT activity by 50-100%. Similar rises in NAT activity were observed following intraocular treatment of ether-anesthetized chickens with muscimol, baclofen and GABA. In contrast to NAT, there was no effect of the tested drugs on the retinal HIOMT activity. Aminophylline (a phosphodiesterase inhibitor) markedly elevated the retinal NAT activity, and a combined treatment with the GABA-ergic drugs and aminophylline resulted in additive effects. The actions of both muscimol and baclofen were antagonized by picrotoxin and bicuculline (two GABA-A receptor blockers), whereas the effect of baclofen was not changed by a selective GABA-B receptor blocker, CGP 35,348. Melatonin given ip significantly raised NAT activity, and its combination with muscimol further stimulated the enzyme. Picrotoxin and bicuculline given to chickens during the dark phase of 12 h light--12 h dark illumination cycle significantly suppressed the nocturnal NAT activity in retina. Neither GABA nor muscimol and baclofen significantly affected basal and forskolin (1 microM)-stimulated adenylate cyclase activity in vitro in light-exposed chicken retina. It is concluded that a GABA signal (acting through type A of GABA receptors) plays an important role in a complex mechanism regulating the rhythmic melatonin biosynthesis in vertebrate retina.

Acetylserotonin O-Methyltransferase↗
PubMed1992

Functionally relevant gamma-aminobutyric acidA receptors: equivalence between receptor affinity (Kd) and potency (EC50)?

Many neurotransmitter receptors bind agonists with high affinity (Kd in the nanomolar range), whereas micromolar concentrations of the same agonists are required to elicit a functional effect. We have identified low affinity agonist binding sites for the gamma-amino-butyric acidA (GABAA) receptor-chloride channel under conditions normally used in 36Cl- uptake assays (a measure of receptor function). The GABAA agonist [3H]muscimol bound to a population of receptors with a Kd (2 microM) similar to its EC50 value for 36Cl- uptake. Binding was inhibited by the GABA agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and by the GABA antagonist bicuculline methiodide. A reduction in the number of [3H]muscimol binding sites (Bmax) by a thiol-modifying reagent produced a corresponding decrease in the Emax for muscimol. The benzodiazepine diazepam enhanced the potency of muscimol in ion flux experiments but did not alter the affinity of [3H]muscimol binding sites. We propose that benzodiazepines enhance GABAergic function by increasing receptor-ion channel coupling, rather than by increasing GABAA receptor affinity. These studies suggest that the study of physiologically relevant (low affinity) binding sites is necessary when examining regulation of receptors by cellular processes, drugs, and disease.

Animals↗
PubMedDate not supplied

The effect of single and prolonged ethanol administration on the sensitivity of central GABA-A and benzodiazepine receptors in vivo.

The response of GABA-modulin to various doses of diazepam and muscimol was used as an index of the sensitivity of central benzodiazepine and GABA-A receptors, respectively. Diazepam and muscimol induced a dose-dependent increase in cytosol GABA-modulin activity in rat nucleus accumbens, hippocampus and cerebellum. A single dose of ethanol (1 g/kg po) potentiated the action of diazepam and muscimol. Prolonged treatment with ethanol (5 g/kg/day for 21 days) did not affect the action of diazepam. In contrast, the effect of muscimol was greatly reduced. In the rats pretreated for 21 days with ethanol five times higher doses of muscimol than in control group were necessary to induce a statistically significant increase of GABA-modulin in the cytosol of the nucleus accumbens, hippocampus and cerebellum. Those results show that a single dose of ethanol enhances GABA-ergic transmission, whereas prolonged treatment with ethanol induces subsensitivity of GABA-A but not benzodiazepine receptors in the limbic system and in cerebellum.

Animals↗
PubMed1988

gamma-Aminobutyric acid-activated chloride channels: relationship to genetic differences in ethanol sensitivity.

We demonstrated recently that low concentrations of ethanol enhanced the muscimol-stimulated chloride influx in cerebellar membranes from long sleep (LS-ethanol sensitive) mice, but had no effect on membranes from short sleep (SS-ethanol resistant) mice. The LS and SS were selected from a heterogeneous stock (HS) of mice for differential sensitivity to the hypnotic effects of ethanol as measured by the duration of the loss of the righting reflex (sleep time). In the present study, we tested 100 HS for ethanol sleep time. The mice with the shortest sleep time (HS-SS) and the mice with the longest sleep time (HS-LS) were selected and tested for the effect of ethanol and muscimol on chloride flux in cerebellum. The effects of ethanol and muscimol on both cerebellar and cortical chloride flux were also examined in rats from the 7th generation selected for differential sensitivity to the hypnotic effects of ethanol (high acute ethanol sensitive rats-HAS and low acute ethanol sensitive rats-LAS). Low concentrations of ethanol (10-30 mM) potentiated muscimol stimulation of 36Cl- uptake in both cortical and cerebellar membranes prepared from ethanol-sensitive animals (HS-LS and HAS). None of the ethanol concentrations tested altered stimulated chloride uptake in ethanol-resistant animals (HS-SS and LAS). No differences in muscimol stimulation of chloride uptake were observed between the pairs of selected lines. These findings strongly suggest that genetic differences in ethanol hypnosis are related to differences in the sensitivity of gamma-aminobutyric acid-operated chloride channels to ethanol.

Animals↗
PubMed1988

Inhibition of the GABA receptor-gated chloride ion channel in brain by noncompetitive inhibitors of the nicotinic receptor-gated cation channel.

The ability of various noncompetitive inhibitors (NCI) of the nicotinic acetylcholine receptor to inhibit gamma-aminobutyric acidA (GABA) receptor activity in brain was investigated. Micromolar concentrations of NCI such as tetraphenylphosphonium, mepacrine, chlorpromazine and phencyclidine inhibited muscimol-induced 36chloride (36Cl-) uptake in rat cerebral cortical synaptoneurosomes in a noncompetitive manner. D-Tubocurarine behaved as a competitive inhibitor. In experiments measuring the time course of muscimol-induced 36Cl- uptake, a decline in the apparent transport rate constant (k') (reflection of desensitization) occurred over the first 3 sec. At lowered temperature (22 degrees C) the k' did not decline during the first 4 sec. Under these conditions preincubation of the vesicles with tetraphenylphosphonium caused a marked decline in the apparent k' over the first 5 sec (transition T1/2 of 1.04 sec) suggesting that tetraphenylphosphonium promotes desensitization of the GABA receptor. The inhibition of muscimol-induced 36Cl- uptake by NCI was reduced in the absence of Ca++. In addition, Ca++ decreased the potency of muscimol to stimulate 36Cl- uptake with an IC50 = 64 microM. The interaction of NCI with GABA agonist and convulsant sites associated with the GABA receptor-gated Cl- channel also was investigated. NCI antagonized noncompetitively [3H]t-butylbicycloorthobenzoate binding to convulsant sites whereas only mepacrine and chlorpromazine antagonized binding of [3H]muscimol to agonist sites. These findings suggest that 1) inhibition of the GABA receptor-gated Cl- channel by NCI may explain the convulsant properties of several of these compounds and 2) there may be structural domains common to the GABA receptor and nicotinic receptor-gated ion channels that selectively permit interactions with various NCI.

Animals↗
PubMed1989

Activation of GABAA receptors causes presynaptic and postsynaptic inhibition at synapses between muscle spindle afferents and motoneurons in the spinal cord of bullfrogs.

The functional role of GABAA receptors in inhibition of synaptic transmission between muscle spindle afferents and spinal motoneurons was studied in the isolated spinal cord of bullfrogs. Extracellular recording from the ventral root showed that activation of GABAA receptors by muscimol (primarily a GABAA receptor agonist) at 50 microM produced a 38% reduction in the amplitude of the excitatory postsynaptic potential (EPSP) evoked by stimulation of triceps muscle sensory afferents and a 66% reduction in the EPSP half-width, suggesting a large increase in the conductance of the motoneuronal membrane. Quantal analysis of unitary triceps EPSPs recorded intracellularly from motoneurons showed that muscimol reduced the quantal content of release (presynaptic inhibition). In addition, muscimol decreased the quantal size (postsynaptic inhibition) when the postsynaptic conductance change was large. Because the effects of muscimol were completely and reversibly blocked by 100 microM bicuculline (a specific GABAA receptor antagonist), both the pre- and the postsynaptic inhibition caused by muscimol were due to activation of GABAA receptors. Activation of GABAA receptors thus causes both pre- and postsynaptic inhibition of synaptic transmission between muscle afferents and spinal cord motoneurons in the frog.

Animals↗
PubMed1988

Development of GABAA receptors in the central visual structures of rat brain. Effect of visual pattern deprivation.

The postnatal development of high-affinity 3H-muscimol binding to GABAA receptors was studied in the lateral geniculate nucleus, superior colliculus, frontal and visual cortex of the rat brain. In the lateral geniculate nucleus 3H-muscimol binding rises from day 10 through day 37 reaching the highest value during the entire development followed by a slight decrease until adulthood. In the superior colliculus 3H-muscimol binding increased continuously from day 10 through day 37, and then decreased until day 50 reaching the adult value. In the visual and frontal cortex, binding reached the highest levels on days 14 and 25, respectively, persisted until day 37 followed by a slight decrease until adulthood. The ontogeny of 3H-muscimol binding sites in the visual regions does not essentially differ from that in other brain regions, suggesting that the appearance of 3H-muscimol binding sites in the visual system is not correlated with the functional maturation of the visual system. Unilateral eyelid closure from day 11 until day 25 did not affect the development of GABAA receptors in any of the central visual regions examined, indicating the lack of environmentally controlled mechanism.

Animals↗
PubMed1986

Separate subunits for agonist and benzodiazepine binding in the gamma-aminobutyric acidA receptor oligomer.

The gamma-aminobutyric acidA (GABAA) agonist muscimol can be photoactivated by 254 nm illumination to affinity label its binding site in the GABAA receptor. We have conducted this reaction on the pure receptor from bovine cerebral cortex in detergent solution, showing that [3H]muscimol can produce then a specific saturable labeling. In the detergent solution, the receptor alone is sensitive to 254 nm irradiation; this reduces the efficiency of incorporation to below that in the membranes, but the competing photoreaction with [3H]muscimol is sufficient and occurs at a representative set of the muscimol-binding sites, such that it can be employed for the photolabeling of those sites. The affinity of [3H]muscimol displayed in this irreversible reaction is indistinguishable from that of its reversible binding. gamma-Aminobutyric acid and bicuculline compete in the photolabeling reaction according to their known affinities at the gamma-aminobutyric acid-binding site. The labeling is shown to occur at the beta-subunit (apparent Mr 57,000) in the pure receptor. The binding sites for gamma-aminobutyric acid agonists, on the beta-subunits, and the benzodiazepine binding sites, on the alpha-subunits, are linked allosterically so that a strongly cooperative hetero-oligomeric structure of this receptor is deduced.

Animals↗
PubMed1986

Autoradiographic localization of GABAergic and muscarinic cholinergic receptor sites in the visual system of the kitten.

The distribution of binding sites for [3H] muscimol (which binds to GABA, receptor) and [3H] QNB (which binds to muscarinic cholinergic receptor) was studied in visual areas of 5 week-old kittens using contact film autoradiography after incubation in vitro of brain sections. A distinct laminar localization of [3H] muscimol receptor sites was observed in young animals with the highest density in layers II/ III and IV of all cortical areas that were investigated. For [3H] QNB binding a laminar pattern of distribution was also found with labeling in layer V exceeding that in adjacent layers. A small intracortical regional variability was noted, for both of the investigated neuroreceptors. [3H] muscimol labeling of the lateral geniculate nucleus and superior colliculus was weaker in comparison to that found in the cortex. The superficial layers of the superior colliculus revealed a high density of [3H] muscimol and [3H] QNB binding sites. The laminar and regional variations in the distribution of [3H] muscimol and [3H] QNB binding sites observed in young kittens, may be related to the possible role of GABAergic and muscarinic receptors in regulation of plastic changes that occur after visual deprivation.

Animals↗
PubMed1986

Behavioral function of GABA in the median raphe nucleus.

Locomotor hyperactivity of rats was induced by injection of muscimol into the median raphe nucleus. Intra-raphe injection of picrotoxin or bicuculline failed to influence locomotor activity, however, muscimol-induced hyperactivity was inhibited by simultaneous intra-raphe injection of picrotoxin and muscimol. These data indicate an involvement of the GABAergic system in the median raphe nucleus in induction of locomotor effects. Systemic and intra-raphe injection of cyproheptadine depressed muscimol-induced hypermotility, whereas lesion of serotonergic raphe neurons by 5,7-DHT or intra-raphe injected LSD did not influence the muscimol effect, suggesting that GABAergically induced locomotor effects are not entirely mediated by serotonergic mechanisms.

Animals↗
PubMed1984

In vitro characterization of benzodiazepine receptor agonists, antagonists, inverse agonists and agonist/antagonists.

Using an extensively washed membrane preparation and standardized incubation conditions, the actions of benzodiazepine (BZ) receptor ligands were evaluated on [3H]flunitrazepam [+/- 10 microM gamma-aminobutyric acid (GABA)], [3H]muscimol (+/- 2.5 microM etazolate) and [35S]butyl bicyclophosphorothionate (TBPS) binding. Classical BZ receptor agonists stimulated [35S]TBPS binding and [3H]muscimol binding in the presence of etazolate. These agents also possessed ratios for [3H]flunitrazepam binding in the absence and presence of GABA (GABA ratio) of 2 to 5. BZ antagonists and inverse agonists had GABA ratios less than 1 and did not alter, or reduced, both [35S]TBPS and [3H]muscimol (+etazolate) binding. The nonsedating BZ agonist/antagonist agents CGS 9896, CL 218872, PK 8165 and PK 9084 all possessed GABA ratios between 1.1 and 1.4 and only stimulated [35S]TBPS and [3H]muscimol (+etazolate) binding to approximately 50% of the level of classical BZ agonists. The BZ partial agonists CGS 9895 and RU 39419 both were unique in that they possessed GABA ratios of 1 or less, stimulated [35S]TBPS binding and had no effect on [3H]muscimol binding (+etazolate). Therefore, by monitoring the major components of the BZ receptor complex (BZ receptor, GABA receptor and chloride channel), we were able to distinguish between different BZ drugs and to support suggestions that these drugs act via unique BZ receptor populations which possess differential couplings to the GABA receptor and chloride channel.

Animals↗
PubMed1984

[35S]-t-butylbicyclophosphorothionate binding sites are constituents of the gamma-aminobutyric acid benzodiazepine receptor complex.

t- Butylbicyclophosphorothionate ( TBPS ), a derivative of potent GABA antagonistic cage convulsants, has recently been introduced ( Squires , R. F., J.E. Casida , M. Richardson, and E. Saederup (1983) Mol. Pharmacol. 13:326-336) as ligand for a GABA-A receptor-linked drug receptor. Using conventionally prepared washed membrane fractions from rat cerebral cortex, we have confirmed that in the presence of 200 mM NaBr [35S] TBPS binds to a high affinity population of binding sites (Kd 26 +/- 5 nM) and that muscimol inhibits [35S] TBPS binding (IC50 0.32 microM) allosterically. In 200 mM NaCl the apparent affinity of [35S] TBPS binding sites is lower (Kd 60 +/- 5 nM), and muscimol has biphasic effects with stimulation at low concentrations of muscimol (EC50 0.023 microM) followed by inhibition at high concentrations (IC50 0.72 microM). Both base line [35S] TBPS binding (in 200 mM NaCl) and muscimol inhibition of [35S] TBPS binding (in 200 mM NaBr) are bidirectionally modulated by the occupancy of benzodiazepine receptors with its ligands. Benzodiazepine receptor agonists, regardless of their structure, enhance and inverse benzodiazepine receptor agonists inhibit base line [35S] TBPS binding and muscimol inhibition of [35S] TBPS binding. Fourteen ligands for benzodiazepine receptors display a similar in vitro profile as benzodiazepine receptor agonists or inverse benzodiazepine receptor agonists on [35S] TBPS binding as their anti- or proconvulsive effects in vivo suggest (Jensen, L. H., E. N. Petersen, and C. Braestrup (1983) Life Sci. 33: 393-399). That [35S] TBPS binding sites are constituents of a GABA benzodiazepine receptor complex is also suggested by a number of membrane pretreatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Microinjections of GABAergic agents in the locus coeruleus modify the gain of vestibulospinal reflexes in decerebrate cats.

1. Precollicular decerebrate cats show a good postural activity in the four limbs and a small-amplitude vestibulospinal (VS) reflex, as revealed by recording the EMG response of the triceps brachii to sinusoidal roll tilt of the animal at 0.15 Hz, +/- 10 degrees. This preparation was used to study whether inactivation of the locus coeruleus (LC) elicited by local administration either of the GABA-A agonist muscimol or of the GABA-B baclofen produced changes in posture as well as in gain of the VS reflexes. 2. Microinjection into the LC of one side of 0.13-0.25 microliter of a muscimol or baclofen solution (at 2.5 or 1 microgram/microliter saline, respectively) stained with 5% pontamine, usually decreased the extensor tonus in the ipsilateral limbs and to a lesser extent also in the contralateral limbs. However, the amplitude of modulation and thus the gain of the first harmonic component of the multiunit EMG responses of the ipsilateral and to a lesser extent also of the contralateral triceps brachii to the same parameters of labyrinth stimulation increased. The phase angle of the responses remained nearly unchanged by this treatment. The effects appeared 5-10 min after the injection of muscimol, fully developed in 30 min and progressively declined within the following 2-2.5 hours. 3. The increased gain of the VS reflexes acting on the triceps brachii did not depend on the decreased postural activity following the injection of the GABA-A or GABA-B agonist, since it was still observed if the reduced EMG activity following the injection was compensated by an increased static stretch of the muscle. Moreover, the postural and reflex changes described above were not due to irritative events following the injection, since they were not observed in control experiments following injection of 0.25 microliter saline within the LC-complex. On the other hand, postural and reflex changes opposite in sign to those elicited by muscimol or baclofen were obtained by local injection into the LC-complex of a GABA-A or GABA-B antagonist (0.25 microliter of bicuculline or faclofen at 8 micrograms/microliters saline). 4. In some experiments, the decrease in postural activity of the forelimbs after injection of muscimol into the LC complex was followed by transient episodes of postural atonia, which affected not only the ipsilateral but also the contralateral triceps muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

GABAergic effects on nucleus tractus solitarius neurons receiving gastric vagal inputs.

Single units in the region of the medial nucleus tractus solitarius (NTS), responding to electrical stimulation of gastric vagal fibers, were recorded in an in vitro neonatal rat brainstem-gastric preparation. gamma-Aminobutyric acid (GABA) subreceptor agonists and antagonists were applied to the gastric and brainstem compartments of the bath chamber to evaluate the peripheral gastric and central brainstem GABAergic effects on NTS neuronal activity. The gastric effects of the GABAA receptor agonist muscimol and GABAB receptor agonist baclofen were evaluated on 55 tonic units that received the gastric vagal inputs. For approximately 58% (32 of 55) and 38% (21 of 55) of the units observed, muscimol (30 microM; IC50 = 2.0 microM) and baclofen (30 microM; IC50 = 1.5 microM) in the gastric compartment induced a concentration-dependent inhibition of 36.2 +/- 3.1% (mean +/- S.E.) and 31.0 +/- 2.9% of the control level of the NTS neuronal activity, respectively. The brainstem effects of muscimol and baclofen were tested on 51 units. For approximately 90% (46 of 51) and 78% (40 of 51) of the units tested, muscimol (30 microM; IC50 = 1.3 microM) and baclofen (30 microM; IC50 = 1.1 microM) in the brainstem compartment produced a concentration-dependent inhibition of 54.1 +/- 3.4% and 48.9 +/- 3. 5% of the control level, respectively. The remaining NTS units were not affected by these two GABA agonists. Bicuculline (10 microM) and saclofen (10 microM), the GABAA and GABAB subreceptor antagonists, competitively antagonized the gastric and brainstem effects by muscimol and baclofen, respectively. Our results demonstrated that both GABAA and GABAB receptors in the stomach and brainstem play an important role in activity modulation of the medial NTS neurons receiving gastric vagal inputs in neonatal rats.

Animals↗
PubMed1988

GABAergic modulation of memory with regard to passive avoidance and conditioned suppression task in mice.

The role of GABAergic neuronal system in learning and memory was investigated using the step-down typed passive avoidance and rapidly learned conditioned suppression tasks in mice. GABA antagonists, picrotoxin and bicuculline, or a GABA synthesis inhibitor, 3-mercaptopropionic acid (3-MP), were administered just after the training test. All of these drugs caused amnesia: they shortened the step-down latency (SDL) and attenuated the conditioned suppression of motility in the retention test conducted 24 h after the administration. Furthermore, we investigated the effect of GABA receptor agonists, muscimol and baclofen, or a GABA transaminase inhibitor, aminooxyacetic acid (AOAA), on these amnesia models. GABA agonists showed an antiamnesic action as follows: in the passive avoidance task, 1) picrotoxin-induced amnesia was antagonized by muscimol, baclofen and AOAA. 2) Bicuculline-induced amnesia was antagonized by muscimol and AOAA but not by baclofen. 3) 3-MP-induced amnesia was antagonized only by muscimol. 4) In the rapidly learned conditioned suppression task, picrotoxin-, bicuculline- and 3-MP-induced amnesia were antagonized by muscimol, baclofen and AOAA. These results suggest that the GABAergic neuronal system plays an important role in the memory retention of passive avoidance and rapidly learned conditioned suppression tasks.

4-Aminobutyrate Transaminase↗