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PubMed1994

The effect of cyclopyrrolones on GABAA receptor function is different from that of benzodiazepines.

The effects of the cyclopyrrolones zopiclone and suriclone on the function of the central gamma-amino-butyric acid type A (GABAA) receptor complex in mouse brain were evaluated both in vitro and in vivo. Added in vitro to mouse cerebral cortical membranes, these compounds potently inhibited [3H]flumazenil binding with IC50 (50% inhibitory concentration) values of 35.8 nM (zopiclone) and 1.1 nM (suriclone). Similar results were obtained with cerebellar membranes, indicating that these drugs do not discriminate between putative type I and type II benzodiazepine receptors. The interaction of cyclopyrrolones with recognition sites present at the level of the GABA receptor complex appears to be competitive, because zopiclone decreased the affinity of the receptors for [3H]flumazenil without affecting the maximal number of binding sites. Moreover, zopiclone and suriclone did not affect the rate of dissociation of [3H]flumazenil from benzodiazepine receptors. The in vitro efficacy of zopiclone appeared different from that of suriclone and the benzodiazepines diazepam and flunitrazepam. Thus, zopiclone failed to affect muscimol-stimulated 36Cl- uptake and only slightly inhibited t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding. In contrast, like diazepam and flunitrazepam, suriclone increased muscimol-stimulated 36Cl- uptake and markedly inhibited [35S]TBPS binding. In contrast, like diazepam and flunitrazepam, suriclone increased muscimol-stimulated 36Cl- uptake and markedly inhibited [35S]TBPS binding. On the other hand, suriclone, like zopiclone, did not modify [3H]muscimol binding to mouse cerebral cortical membranes. Moreover, zopiclone antagonized the reduction in [35S]TBPS binding elicited by the benzodiazepine receptor full of agonist diazepam. Consistent with its low efficacy in vitro, oral administration of zopiclone (2.5 to 100 mg/kg, p.o.) in mice failed to modify [35S]TBPS binding subsequently measured in cerebral cortical membranes "ex vitro".(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Ontogeny of GABA-ergic and dopaminergic mediation of gnawing behavior in the mouse.

The ontogenetic course of dopaminergically mediated gnawing and the potentiation of this behavior by muscimol (a GABA receptor agonist) was explored in developing and young adult mice using a time-sampling (in 5-, 8-, 11-, and 14-day-old pups), or a corrugated paper procedure (in 14-, 17-, 20-, 23-, 26-, 35-, and 53-day-old animals). In experiment 1, the older mice group (14-53 days), displayed a dose-dependent gnawing behavior after methylphenidate, a dopamine indirect agonist (20, 30, 50 mg/kg). Similarly, in 5-, 8-, 11-, and 14-day-old pups, methylphenidate (10, 20, 50 mg/kg) evoked stereotyped gnawing (or indissociable gnawing-licking in 5-day-old pups), with maximal effects after the two lower doses at 8-11 days of age (experiment 2). Muscimol pretreatment (dosages ranging from 0.025 to 1.3 mg/kg) induced a clear-cut potentiation of gnawing elicited by methylphenidate (10 or 20 mg/kg) as early as 8 days of age (experiments 3 and 4). However, muscimol did not potentiate gnawing in 5-day-old pups treated with 10 or 2.5 mg/kg methylphenidate. The effectiveness of methylphenidate in inducing gnawing-licking among 5-day-old pups confirms the early maturation of central dopamine receptors reported in the literature. It is speculated that the absence of potentiating action of muscimol on methylphenidate-induced gnawing-licking at this age may be due to a functional immaturity of the GABAergic striato-nigro-tectal system, which is thought to transmit dopaminergic striatal stereotyped response at the output stations (recent review by Scheel-Krüger 1986).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1991

Gonadal regulation of GABAA receptors in the different brain areas of the male Japanese quail.

Quantitative autoradiography was used to investigate the distribution and effects of gonadal hormones on [3H] muscimol (specific GABAA receptor ligand) binding in the male Japanese quail brain. In gonadally intact Japanese quail brains, [3H] muscimol revealed a heterogeneous distribution with high GABAA receptor levels in the cerebellum pars granularis (656 fmol/mg wet weight of tissue) and in the pars molecularis (405 fmol/mg wet weight of tissue). Low receptor levels were found in the nucleus preopticus anterior and the nucleus lateralis of the hypothalamic regions (less than 220 fmol/mg wet weight of tissue) as well as thalamic nuclei such as rotundus and pretectalis (220-261 fmol/mg wet weight of tissue). Castration resulted in [3H] muscimol binding changes in both brain areas that contain steroid receptors and brain areas devoid of steroid receptors. In fact, castration led to high binding levels in the preopticus anterior nucleus and in the anterior neostriatum area, brain areas that are known to contain gonadal steroid receptors. Castration also elevated [3H] muscimol binding in the hyperstriatum ventrale and reduced binding levels in the paleostriatum augmentatum and the stratum griscum centrale area; all of these areas are known to be devoid of gonadal steroid receptors. At this point it was also important to know whether the gonadal steroid effect is due to alterations in the number of binding sites (Bmax) and/or the affinity binding state (KD). The saturation binding study, dealing with some of the areas described above in brains of male quails castrated or castrated and treated with testosterone or estradiol, demonstrated that the steroid replacement therapy was responsible for the changes of the Bmax.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1980

Evidence for a GABAergic nigrothalamic pathway in the rat. I. Behavioural and biochemical studies.

Unilateral stereotaxic microinjection of muscimol into the caudal region of the substantia nigra (SN) evoked tight, dose-related contralateral locomotor asymmetry and stereotypy. These behaviours were partially attenuated by various pretreatments, including 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway, intraperitoneal (i.p.) haloperidol, and inhibition of thalamic GABA-transaminase activity by local intrathalamic injection of ethanolamine-O-sulphate. Electrolytic or kainic acid lesions of the medial thalamic nuclei (MTN) partially reduced the contraversive rotation to intranigral muscimol, and completely abolished the similar behaviour elicited by apomorphine (25 microgram) injected into the ipsilateral caudate nucleus. Contraversive turning to intranigral muscimol was completely inhibited by kainic acid lesions of the ipsilateral SN, but potentiated by intrahalamic injection of picrotoxin. Muscimol (40 ng--4 microgram) administered to the MTN complex in one hemisphere stimulated rats to move in ipsilateral circles that were unaffected by haloperidol. The results of these behavioural experiments suggest that the nigrostriatal dopamine pathway, the nigrothalamic projection and possibly other non-dopaminergic SN efferents all play important roles in mediating the influences of the SN on motor and stereotyped behaviours. Disruption of the nigrothalamic pathway following electrical or chemical injury to the SN was accompanied by falls in GABA and its synthesising enzyme in the corresponding MTN. These data, together with the findings of our electrophysiological study presented in the following paper, are consistent with the nigrothalamic system having a GABAergic inhibitory function.

Animals↗

PubMed1989

Longer term progesterone treatment induces changes of GABAA receptor levels in forebrain sites in the female hamster: quantitative autoradiography study.

Quantitative receptor autoradiography was applied to evaluate the effects of one and three injections of 1 mg progesterone (P) on 3H muscimol binding levels in the different forebrain areas of the female hamster. The overall effect of P resulted in substantial increases in 3H muscimol binding in brain areas containing gonadal steroid receptors: medial preoptic area and ventromedial hypothalamic nucleus as well as in bed nucleus stria terminalis and subiculum. Similarly, the caudate putamen, a region where gonadal steroid receptors are not abundant, also showed substantial increases of 3H muscimol binding receptor levels. Moreover, female hamsters treated with P for 3 days presented altered 3H muscimol binding levels in the amygdala and thalamic nucleus that were, in some cases, not produced by one dose of P. P treatment also decreased GABAA binding in two areas of the thalamus. These results are consistent with the proposal that P may alter GABAergic inhibitory activity via changes in the levels of GABAA receptors in certain forebrain areas in the female hamster, changes which may be linked to the mediation of anxiolytic effects and to the inhibition of aggressive behavior. These data also suggest that P treatment increases the binding of high affinity GABA receptors in some forebrain sites and may be responsible for maintenance of the anxiolytic effects.

Animals↗

PubMed1979

Modification of the behavioural effects of amphetamine by a GABA agonist in a primate species.

Acute administration of d-amphetamine in the marmoset results in a dose dependent increase in small head movements (checking), and an almost total suppression of purposeful activities and social interaction. It has little effect on locomotion and does not induce stereotyped gnawing. The GABA-agonist, muscimol, decreases checking, locomotion, activities and social interaction when given alone, but induces jerking movements at large doses. When administered in combination with amphetamine, muscimol induces persistent stereotyped gnawing. On the basis of the present findings and those of experiments in rodents it is suggested that compulsive gnawing results from overactivity in the striatal efferent pathway, while checking is probably mediated by extra-striatal sites. Since the behavioural effects of muscimol resemble those of the typical neuroleptics with the exception of the induction of gnawing, it is suggested that muscimol, though sedative, may counteract certain extrapyramidal effects of neuroleptic treatment while facilitating their other behavioural effects.

Animals↗

PubMed1992

Autoradiographic localization of gamma-aminobutyric acidA receptors within the ventral tegmental area.

Destruction of intrinsic neurons in the ventral tegmental area (VTA) with the excitotoxin, quinolinic acid produced a significant decrease (80%) in [3H]muscimol binding to GABAA receptors within the parabrachial pigmented and paranigral nuclei of the VTA. Selective destruction of the dopaminergic neurons with 6-hydroxydopamine (6-OHDA) did not reduce [3H]muscimol binding within the VTA. However, the destruction of dopaminergic neurons did produce an increase (20%) in [3H]muscimol binding contralateral to the lesion, suggesting a reduction in the GABAergic innervation to this region. Additionally, destruction of the VTA afferents with quinolinic acid injections in the medial accumbens failed to produce alterations in [3H]muscimol binding within the VTA. These results are consistent with the predominant localization of GABAA receptors to non-dopaminergic neurons intrinsic to the VTA.

Animals↗

PubMed2005

Increased density of GABAA receptors in the superior temporal gyrus in schizophrenia.

The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In a previous study we reported a decrease in the density of M1 and M2/M4 muscarinic receptors in the STG in schizophrenia. In this study, we investigated the density of GABA(A) receptors in the left STG of schizophrenia patients compared to control subjects. We used quantitative autoradiography to investigate the binding of the agonist [(3)H] muscimol to GABA(A )receptors in the STG. A significantly higher density of [(3)H] muscimol binding was observed in the upper three quarters of the STG grey matter (corresponding to layers I-IV) than in the lower one-quarter (layers V-VI) in both groups. A significant increase (about 30%, P<0.05) in binding of [(3)H] muscimol was clearly observed in schizophrenia patients compared to control subjects. There were no significant correlations between [(3)H] muscimol binding density and age, post-mortem interval, brain pH or final recorded antipsychotic drug use. These results suggest an increase of GABA(A) receptor densities in the STG of schizophrenia patients.

Adaptation, Physiological↗

PubMed1999

Activity-dependent development of cortical axon terminations in the spinal cord and brain stem.

Corticospinal (CS) axon terminations in several species are widespread early in development but are subsequently refined into a spatially more restricted distribution. We studied the role of neural activity in sensorimotor cortex in shaping postnatal development of CS terminations in cats. We continuously infused muscimol unilaterally into sensorimotor cortex to silence neurons during the postnatal CS refinement period (weeks 3-7). Using anterograde transport of WGA-HRP, we examined the laterality of terminations from the muscimol-infused (i.e., silenced) and active sides in the spinal cord, as well as in the cuneate nucleus and red nucleus. We found that CS terminations from the muscimol-infused cortex were very sparse and limited to the contralateral side, while those from the active cortex maintained an immature bilateral topography. Controls (saline infusion, noninfusion) had dense, predominantly contralateral, CS terminations. There was a substantial decrease in the spinal gray matter area occupied by terminations from the side receiving the blockade and a concomitant increase in the area occupied by ipsilateral terminations from the active cortex. Optical density measurements of HRP reaction product from the active cortex in muscimol-infused animals showed substantial increases over controls in the ratio of ipsilateral to contralateral CS terminations for all laminae examined (IV-V, VI, VII). Our findings suggest that ipsilateral dorsal horn terminations reflect new axon growth during the refinement period because they are not present there earlier in development. Those in the ventral horn are present earlier in development and thus could reflect maintenance of transient terminations. Increased ipsilateral terminations from active cortex were due to recrossing of CS axons in lamina X and not to an increase in labeled CS axons in the ipsilateral white matter. Examination of brain stem terminations suggested that, between postnatal weeks 3 and 7, development of corticocuneate terminations also is activity-dependent but that development of corticorubral terminations is not. Activity-dependent CS development is a plausible mechanism by which early motor experiences could shape the anatomical and functional organization of the motor systems during a critical postnatal period.

Aging↗

PubMed2000

Functions of the nucleus of the optic tract (NOT). I. Adaptation of the gain of the horizontal vestibulo-ocular reflex.

We studied the role of the nucleus of the optic tract (NOT) in adapting the gain of the angular vestibulo-ocular reflex (aVOR) in rhesus and cynomolgus monkeys using lesions and temporary inactivation with muscimol. The aVOR gain was adaptively reduced by forced sinusoidal rotation (0.25 Hz, 60 degrees/s) in a self-stationary visual surround, i.e., a visual surround that moved with the subject, or by wearing x0.5 reducing lenses during natural head movements. The aVOR gains dropped by 20-30% after 2 h and by about 30% after 4 h. Muscimol injections caused a loss of adaptation of contraversive-eye velocities induced by the aVOR, and their gains promptly returned to or above preadapted levels. The gains of the adapted ipsiversive and vertical eye velocities produced by the aVOR were unaffected by muscimol injections. Lesions of NOT significantly reduced or abolished the animals' ability to adapt the gain of contraversive aVOR-induced eye velocities, and the monkeys were unable to suppress these contraversive-eye velocities in a self-stationary surround. The lesions did not affect ipsiversive aVOR-induced eye velocities, and the animals were still able to suppress them. Lesions of NOT also affected the unadapted or "default" aVOR gains. After unilateral NOT lesions, gains of ipsiversive aVOR-induced eye velocity were reduced, while gains of contraversive aVOR-induced eye velocity were either unaffected or slightly increased. Consistent with this, muscimol injections into the NOT of unadapted monkeys slightly reduced the gains of ipsiversive and increased the gains of contraversive-eye velocities by about 8-10%. We conclude that each NOT processes ipsiversive retinal-slip information about visual surround movement relative to the head induced by the aVOR. In the presence of visual surround movement, the retinal-slip signal is suppressed, leading to adaptive changes in the gain of aVOR-induced contraversive horizontal eye velocities. NOT also has a role in controlling and maintaining the current state of the aVOR gains. Thus, it plays a unique role in producing and supporting adaptation of the gain of the horizontal aVOR that is likely to be important for stabilizing gaze during head movement. Pathways through the inferior olive are presumably important for this adaptation.

Adaptation, Physiological↗

PubMed1982

Medullary ventral surface GABA receptors affect respiratory and cardiovascular function.

We previously demonstrated that GABA and muscimol administered either into the cisterna magna or the fourth ventricle to chloralose-anesthetized cats cause respiratory depression, hypotension, and bradycardia. Injection of these substances into the lateral and third ventricles had no effect. In order to localize the site of action, muscimol and GABA were applied by Perspex rings to the ventral surface of the medulla. Application of muscimol (0.25-2.66 micrograms) to Schlaefke's area in 6 cats reduced minute ventilation from 443 +/- 38 to 291 +/- 52 ml/min by reducing tidal volume from 31.8 +/- 2.3 to 17.6 +/- 1.4 ml, without changing respiratory rate and duration of inspiration. Hypotension and bradycardia were also observed. Application of GABA (0.14-4.86 mg) produced similar effects on respiratory activity and arterial blood pressure. No significant effects occurred when high doses of these agents were applied to Loeschcke's and Mitchell's areas. Application of bicuculline (5-25 micrograms) to Schlaefke's area had the opposite effect of muscimol and GABA on respiratory activity and blood pressure, and reversed the respiratory and cardiovascular depressant effects of both agents. We conclude that GABA receptors are present at Schlaefke's area, and that activation of these receptors results in respiratory depression, hypotension, and bradycardia. Our results suggest that GABA may be an important inhibitory neurotransmitter in the modulation of respiratory and cardiovascular control.

Animals↗

PubMed1984

GABAergic mechanisms in mediating muscular rigidity, catalepsy and postural asymmetry in rats: differences between dorsal and ventral striatum.

In rats, the GABAergic agonist muscimol was injected unilaterally either into the mid ventroposterior striatum (ventral striatum) or into the mid dorsoposterior striatum (dorsal striatum), and the following parameters were estimated: (1) a tonic activity in the electromyogram (EMG) recorded from the gastrocnemius-soleus (GS) muscle, which appears to reflect a muscular rigidity; (2) catalepsy, and (3) asymmetries in posture. Injection of muscimol (25 or 50 ng) into the ventral striatum produced tonic EMG activity, catalepsy and ipsiversive posture; these signs were much less pronounced or not observed after injections into the dorsal striatum. Co-administration of bicuculline (500 ng) into the ventral striatum, or simultaneous injection of muscimol (25 ng) into the substantia nigra pars reticulata (SNR), antagonized both the tonic EMG activity and the catalepsy produced by injection of 50 ng muscimol into the ventral striatum. These results seem to support the assumption that all 3 symptoms mentioned can be produced by an inhibition of striatonigral GABAergic neurones. These symptoms are probably due to a disinhibition of nigrofugal neurones, originating in the SNR.

Animals↗

PubMed1985

Modulation of synaptic GABA receptor binding by membrane phospholipids: possible role of active oxygen radicals.

Pretreatment of cerebral synaptic membrane preparations with phospholipase (PLase) A2 invariably induced a significant enhancement of [3H]muscimol binding in a dose-dependent manner with a concomitant elevation of the content of total free fatty acids in the membrane. In vitro addition of various free fatty acids exhibited no profound alteration in [3H]muscimol binding, whereas a significant enhancement of the binding was induced by the pretreatment of the membrane with unsaturated free fatty acids such as arachidonic acid and linoleic acid, but not by that with saturated free fatty acids. None of the inhibitors of arachidonic acid metabolism including indomethacin (an inhibitor of cyclo-oxygenase) and nordihydroguaiaretic acid (an inhibitor of lipoxygenase), however, had a significant preventive action on the augmentation of [3H]muscimol binding. On the other hand, various scavengers for superoxide anion radical such as superoxide dismutase, tiron and nitroblue tetrazolium (NBT) not only suppressed the PLase A2-induced enhancement of [3H]muscimol binding, but also diminished the augmentation of the binding due to PLase C and arachidonic acid. It was also found that a remarkable facilitation of the formation of superoxide anion radical was induced by the treatment of synaptic membrane with PLase A2, PLase C and arachidonic acid, all of which exhibited a prominent stimulation of the binding. In addition, treatment of the membrane with xanthine and xanthine oxidase, a superoxide anion radical generating system, resulted in a profound stimulation of the binding. The PLase A2-induced enhancement of the binding was also attenuated by the scavengers for hydrogen peroxide like catalase as well as by those for hydroxyl radical such as dimethylnitrosoaniline, mannitol, methanol and ethanol, but not by those for singlet oxygen radical including alpha-tocopherol and beta-carotene. The present results suggest that membrane phospholipids may play an important role in the modulation of the association of GABA with its relevant receptor through the generation of active oxygen radicals from unsaturated free fatty acids which are yielded by the catalytic action of PLase A2 and/or PLase C.

Animals↗

PubMed1986

Anterior thalamic mediation of generalized pentylenetetrazol seizures.

The effects of microinjection of various neuroactive compounds into the anterior thalamic nucleus (AN) and other selected subcortical regions of guinea pig brain on the expression of pentylenetetrazol (PTZ)-induced behavioral and electrical seizure activity were examined. Excitatory agents, kainic acid (KA), bicuculline (BIC) or PTZ, injected into the AN or other thalamic nuclei, striatum, but not the mammillary bodies (MB), facilitated the EEG convulsant action of systemically administered PTZ. Injection of muscimol into the AN protected against the expression of PTZ-induced repetitive high-voltage EEG seizure discharges and inhibited the facilitatory effects of subcortically applied KA or BIC. Injection of muscimol into the AN was also able to terminate established ongoing seizure discharges. Unilateral application of muscimol to the AN did not prevent the repetitive hypersynchronous EEG discharges following systemic PTZ but did result in the delay in the onset of cortical hypersynchrony in the ipsilateral hemisphere. Muscimol injections into other thalamic nuclei, MB, cortex, striatum or directly into the CSF space had no anticonvulsant effect, however. Microinjection of gamma-vinyl-gamma-aminobutyric acid, a selective GABA transaminase inhibitor, resulted in protection from the behavioral convulsant action and lethal effects of PTZ when administered into the thalamus, especially the AN, but not when injected into the striatum or CSF. These data demonstrate that the AN is an important subcortical nucleus for the mediation of both cortical EEG synchrony and behavioral seizure expression induced by PTZ. In light of previous results establishing a role for the brainstem and diencephalon in PTZ seizure expression, the AN may serve, in part, as a gating mechanism for the propagation of paroxysmal activity between subcortical areas and the cerebral cortex.

Aminocaproates↗

PubMed1987

Autoradiographic localization of gamma-aminobutyric acid receptors in mouse barrel field.

The distribution of high-affinity gamma-aminobutyric acid (GABA) receptors in mouse posteromedial barrel subfield (PMBSF) in layer IV of the somatosensory (SI) cortex was studied using [3H]muscimol autoradiography in vitro. A qualitative study revealed a heterogeneous distribution in the density of [3H]muscimol binding in the barrel field. In the barrel sides and septum between the barrels [3H]muscimol binding exhibits the lowest level of labelling in the entire tissue. In comparison, [3H]muscimol binding in the hollows is considerably higher than in the barrel sides although the level is not homogeneous. These findings suggest that the barrel hollows are much richer in GABA receptors than the surrounding barrel sides and septa.

Animals↗

PubMed1990

GABA-mediated regulation of feline aggression elicited from midbrain periaqueductal gray.

The midbrain periaqueductal gray (PAG) is now recognized as a critical structure for the initiation and regulation of aggressive behavior in the cat. The PAG is also known to be rich in gamma-aminobutyric acid (GABA) receptors. In the present study, we sought to examine the possible role of this putative neurotransmitter in the modulation of affective defense and quiet biting attack behavior elicited by electrical stimulation of the PAG. Cannula-electrodes were employed for electrical stimulation as well as for microinjections of a GABA agonist (muscimol: 3, 12 and 22 pmol/0.25 microliters) and GABA antagonist (bicuculline: 22 and 68 pmol/0.25 microliters). After establishing predrug response threshold values for affective defense and quiet biting attack, these drugs were microinjected into the PAG sites from which these responses were elicited. Microinjections of muscimol (12 and 22 pmol) significantly suppressed the affective defense response in a dose- and time-dependent manner. Pretreatment with bicuculline (68 pmol) blocked the suppressive effects of muscimol (12 pmol) upon affective defense behavior. In contrast, this dose of muscimol failed to alter the response threshold for quiet biting attack behavior. Microinjections of vehicle alone (0.25 microliter of saline, pH = 7.4) did not modify the thresholds for either of these responses. These results indicate that, at the level of the PAG, GABA-ergic mechanisms are selectively involved in the regulation of affective defense behavior in the cat.

Aggression↗

PubMed1990

Bicuculline and picrotoxin block phase advances induced by GABA agonists in the circadian rhythm of locomotor activity in the golden hamster by a phaclofen-insensitive mechanism.

Permanent phase shifts in the free-running rhythm of locomotor activity of the golden hamster were induced with microinjections of the gamma-aminobutyric acid (GABA) agonists muscimol or baclofen in the hypothalamic suprachiasmatic nuclei. Muscimol and baclofen exhibit relatively high binding affinities for GABAA and GABAB receptors, respectively. Microinjections of the GABA antagonists, bicuculline methobromide or picrotoxinin, thought to block the actions of GABA at GABAA receptors, could block phase shifts induced by muscimol but not the benzodiazepine, triazolam. Microinjections of the postsynaptic GABAB receptor antagonist phaclofen, which blocks the actions of GABA at postsynaptic but not at presynaptic GABAB receptor sites, did not block the phase-shifting actions of either muscimol or baclofen. GABAergic antagonists when given alone did not induce phase shifts. Collectively, these studies indicate that when activated by exogenous GABAergic agents, a GABAergic system associated with both GABAA and GABAB receptors exists as a neural regulatory mechanism that can reset the mammalian circadian clock. However, GABAergic synaptic pathways may not be normally involved in the circadian timing system.

Animals↗

PubMed1992

GABAergic influence on the development of the sexually dimorphic nucleus of male and female rats.

A large number of estrogen-sensitive neurons in rat hypothalamus use gamma-aminobutyric acid (GABA) as a neurotransmitter. As estrogens influence the size of the sexually dimorphic nucleus (SDN) of the preoptic area it was tested whether perinatal treatment of rats with the GABA-agonistic drug muscimol can induce similar changes as estrogens. Male and female rats were treated perinatally with muscimol or with the vehicle only and the vols. of the SDN of the preoptic area were determined morphometrically following maturation of the animals. The SDN vols. in treated males were significantly smaller (80.3%) compared to controls. There was no striking effect in females. Our data suggest an influence of the GABAergic system on the development of the sexually dimorphic nucleus of the preoptic area (SDN-POA). The muscimol treatment, however, did not mimic the effects of perinatal estrogen treatment. Since muscimol is a GABAA receptor stimulating drug it appears that this receptor subtype is not involved in the estrogen-induced changes in size of the SDN.

Animals↗