Showing papers on "GABAergic published in 1982"
TL;DR: The widespread distribution of GABA neurons in spinal cord was suggestive of diverse functions for these cells, encompassing conventional synaptic roles and, perhaps, an involvement in hormonally modulated communication via GABAergic, CSF-contacting neurons.
253 citations
TL;DR: The results from the present series of experiments indicate that ethanol enhances central GABAergic activity.
Abstract: The interaction between ethanol and various GABAergic drugs (muscimol, bicuculline, picrotoxin) with regard to their effects on locomotor activity, drug-induced sleep, body temperature, and convulsions was studied. It was demonstrated that the GABA receptor agonist muscimol potentiated the sedative properties of ethanol, while the opposite effect, a reduction of ethanol-produced sedation, was seen upon administration of the GABA receptor blocking agent picrotoxin. Consequently, the results from the present series of experiments indicate that ethanol enhances central GABAergic activity.
237 citations
169 citations
TL;DR: A large reduction in the number of symmetric synapses at epileptic foci and the increased gliosis indicate that the previously observed loss of GABAergic terminals at sites of focal epilepsy is caused by terminal degeneration.
Abstract: Previous immunocytochemical results from five monkeys with cortical focal epilepsy produced by alumina gel showed a severe decrease at seizure foci of axon terminals that contained glutamic acid decarboxylase (GAD), the synthesizing enzyme for the inhibitory neurotrasmitter, GABA. These data indicated a functional loss of GABAergic terminals but did not show: (1) whether this loss was caused by GABAergic nerve terminal degeneration or by a lack of GAD immunoreactivity within these terminals and (2) if this loss of GABAergic terminals was selective for only this terminal type. To resolve these issues, cortical tissue from three of the five monkeys used in the previous study was reexamined using electron microscopy, and a quantitative morphological analysis of cortical structures was made to compare profiles of terminals and glia in the nonepileptic cortex with those in the focus and parafocus. The following statistically significant changes were observed: (1) the number of axosomatic symmetric synapses with layer V pyramidal cells was decreased 80% at the focus and 50% at the parafocus, (2) in the neuropil adjacent to these pyramidal somata, the number of terminals forming symmetric synapses was reduced 50% at the epileptic focus but was unchanged at the parafocus, while the number of asymmetric synapses was reduced 25% at the focus and 15% at the parafocus, and (3) a 50% increase of glial profiles occurred at epileptic foci both in the neuropil and at sites apposed to pyramidal cell somata. The quantitative results also showed that terminals which form symmetric synapses had twice the number of mitochondria per terminal as those that form asymmetric synapses. Axon terminals which form symmetric synapses with somata and dendrites in the neocortex have been shown previously to contain GAD. Therefore, the large reduction in the number of symmetric synapses at epileptic foci and the increased gliosis indicate that the previously observed loss of GABAergic terminals at sites of focal epilepsy is caused by terminal degeneration. Since such terminals are reduced more severely at epileptic foci than other terminals, their loss could be the basis for seizure activity due to a preferential decrease of inhibitory function at epileptic foci. Hypoxia has been shown to cause a selective degeneration of terminals with the same morphology as GABAergic terminals in the cortex, and the basis for this loss could be related to higher physiological and/or metabolic activities of GABAergic cortical cells which may inhibit other cells tonically. The fact that increased numbers of mitochondria occur in GABAergic terminals supports this idea.
149 citations
TL;DR: Some neuronal elements in the NRD are morphologically, pharmacologically and anatomically similar to 5-HT neurons described at this level, which strongly suggest that a population of GABA neurons could be sensitive to 5,7-DHT and so have the capacity to take up5-HT.
148 citations
TL;DR: The future characterization of this system will provide a better understanding of the involvement of GABA in the physiology of anterior pituitary hormone secretion and will contribute to the development of new pharmacological agents for the therapy of neuroendocrine disorders.
133 citations
Journal Article•
TL;DR: No simple relationship was observed between the degree of motor impairment caused by either ethanol or gamma-acetylenic GABA and changes in GABA concentration in three brain areas, and the interaction does not involve a direct activation of GABA receptors by ethanol.
Abstract: Direct or indirect pharmacological manipulation of gamma-aminobutyric acid (GABA) receptor activity was examined in relation to the motor incoordinating actions of ethanol in the rat. Ethanol (1.13-3.0 g/kg i.p.) caused a dose-dependent increase in the height of aerial righting. This motor impairment was increased selectively by intracisternal injection of the GABA agonists muscimol (0.10 microgram), 4,5,6,7-tetrahydroisoxazole(5,4-c) pyridin(3-ol) (1.0 microgram) and GABA (1000 micrograms). The GABA antagonist, bicuculline (1.0 and 5.0 micrograms intracisternally), reduced impairment. Thus, direct manipulation of GABA receptor activity modulated motor incoordination caused by ethanol. In addition, indirect-acting GABA-mimetics, such as gamma-acetylenic GABA (100 mg/kg i.p.), aminooxyacetic acid (50 mg/kg i.p.), ethanolamine-O-sulfate (250 mg/kg i.p.) and L-2,4-diaminobutyric acid (600 mg/kg i.p.) all potentiated the increase in the height of aerial righting caused by ethanol treatment. Failure of ethanol to modify the binding of [3H]muscimol to cerebral cortical membranes in vitro suggested there was no direct competition for GABA binding sites or facilitation of the binding of GABA to these sites by ethanol. Also, no simple relationship was observed between the degree of motor impairment caused by either ethanol or gamma-acetylenic GABA and changes in GABA concentration in three brain areas. Although GABAergic neurons may be involved in the mechanism underlying ethanol-induced depression of motor coordination, the interaction does not involve a direct activation of GABA receptors by ethanol.
131 citations
Journal Article•
TL;DR: It is suggested that decreased activity in the central GABAergic and dopaminergic system may be involved in the pathogenesis of depression.
121 citations
TL;DR: D,l-Baclofen increased blood pressure and heart rate when injected into the same region, but this effect was not antagonized by bicuculline, and a GABAergic system appears to modulate the cardiovascular regulation within the NTS.
Abstract: Microinjections of GABA and of the specific agonist of GABA receptors, muscimol, in the intermediate nucleus tractus solitarii (NTS) of pentobarbitone anaesthetized cats produced hypertension and tachycardia. The GABA receptor antagonist, bicuculline, had opposite effects and prevented those of muscimol. Therefore, a GABAergic system appears to modulate the cardiovascular regulation within the NTS. d,l-Baclofen also increased blood pressure and heart rate when injected into the same region, but this effect was not antagonized by bicuculline. The mechanism of this action of baclofen is discussed.
108 citations
Journal Article•
TL;DR: Both progabide and SL 75102 exhibit a broad spectrum of anticonvulsant activities against seizures which involve GABA-mediated events or which are apparently independent of GABAergic mechanisms, and support the hypothesis that direct GABA receptor stimulation is an effective means of controlling convulsions of various origins.
Abstract: Progabide (4-([(4-chlorophenyl) (5-fluoro-2-hydroxyphenyl)-methylene]amino) butanamide) is a gamma-aminobutyric acid (GABA) receptor agonist which readily enters the brain. In the body, progabide is metabolized to three active metabolites: SL 75102, gabamide and GABA. Progabide and SL 75102 readily enter the brain and GABA and gabamide are also formed within this organ. Both progabide and SL 75102 exhibit a broad spectrum of anticonvulsant activities against seizures which involve GABA-mediated events (bicuculline, picrotoxinin and pentylenetetrazol) or which are apparently independent of GABAergic mechanisms (penicillin, strychnine, electroshock and audiogenic seizures). These data support the hypothesis that direct GABA receptor stimulation is an effective means of controlling convulsions of various origins. Progabide and SL 75102 have relatively minor secondary effects in comparison to commonly used antiepileptics. Myorelaxation occurs, but only at doses higher than the ED50 values in convulsant tests. Furthermore, these compounds are not sedative. Finally, these GABA agonists have a complex action in the extrapyramidal system. Anticonvulsant doses are antagonistic to dopamine receptor-mediated behaviors, whereas much lower doses seem to facilitate the effects of dopaminergic transmission.
98 citations
Journal Article•
TL;DR: Data suggest a specific agonist action of progabide and SL 75102 on GABA receptors, in agreement with the hypothesis of a GABAergic autoreceptor controlling GABA release from its nerve terminals.
Abstract: Progabide and its immediate metabolite SL 75102 displace [3H]gamma-aminobutyric acid (GABA), [3H]muscimol and [3H]isoguvacine from their binding sites to membranes prepared from rat brain or human cerebellum and increase (SL 75102) [3H]flunitrazepam binding to rat cerebral cortex membranes. In contrast, these compounds have very weak or no effects on alpha or beta noradrenergic, histamine, muscarinic cholinergic or glycine receptors or on the [3H]imipramine or [3H]kainate binding sites. Neither progabide nor SL 75102 inhibit GABA synthesis, metabolism or uptake. Also, the uptake of norepinephrine, serotonin and dopamine into synaptosomes of cerebral regions is not affected by progabide. [3H]GABA release from substantia nigra slices is decreased by SL 75102 and progabide, in agreement with the hypothesis of a GABAergic autoreceptor controlling GABA release from its nerve terminals. These data suggest a specific agonist action of progabide and SL 75102 on GABA receptors.
TL;DR: A method for estimating the rate of the GABA turnover in vivo by measuring the initial rate of GABA accumulation after administration of AOAA or gabaculine is proposed and the validity of the two techniques is discussed.
Abstract: The accumulation of γ-aminobutyric acid (GABA) after inhibition of GABA-T (4-aminobutyrate: 2-oxoglutamate aminotransferase, EC 2.6.1.19) by various doses of aminooxyacetic acid (AOAA) and gabaculine was studied in four different regions of the mouse brain. The dose-response curve for GABA accumulation after treatment with AOAA was linear up to 10 mg/kg i.p., and then leveled off. The increase in GABA accumulation after gabaculine treatment was linear up to 100 mg/kg i.p. No further increase was observed with doses up to 300 mg/kg i.p. The selectivity of both GABA-T inhibitors was assessed by measuring their effects on the content of free amino acids in mouse brain. Apart from the substantial increase in the GABA concentration, there were significant decreases in the content of glutamic acid, aspartic acid, alanine and glutamine, and an increase in ornithine content after administration of gabaculine. The same changes in amino acid content were observed after treatment with AOAA, but the level of lysine was also increased and the change in alanine level was biphasic. All these changes, however, were very small compared with the large increase in GABA level. A method for estimating the rate of the GABA turnover in vivo by measuring the initial rate of GABA accumulation after administration of AOAA or gabaculine is proposed, and the validity of the two techniques is discussed. The effect of diazepam on GABA levels and on the gabaculine-induced accumulation of GABA was studied. The results obtained with diazepam show that this method can provide valuable insight into the effects of drugs on GABAergic mechanisms in vivo.
TL;DR: The uptake of L-glutamine in neuronal and glial cultures derived from rat cerebral hemispheres was found to be mediated by a low affinity-high capacity mechanism which was concentrative in both cell types; the calculated Km and Vmax were twice as high in glial than in neuronal cultures.
TL;DR: Data with muscimol given parenterally, as well as local injections into the substantia innominata, further support an inhibitory function for this pathway in the regulation of the substantianata-cortical cholinergic projection.
TL;DR: The brain can influence the endocrine cells of the pars intermedia directly through GABAergic mechanisms, and the ionic and pharmacological characteristics of this action of GABA resemble those encountered at many GABAergic synapses in the central nervous system (CNS).
Abstract: Evidence that the endocrine cells of the pars intermedia of the mammalian pituitary gland secrete not only melanotropins but corticotropins and endorphins1 heightens interest in the nervous control of these cells. Within the mammalian adenohypophysis the pars intermedia is unique in being directly innervated by neurones whose cell bodies lie in the brain2. However, the nature and function of this innervation is poorly understood. A dopaminergic tract has been identified in rats3,4, which appears to have an inhibitory function5, and dopamine applied directly to isolated rat pars intermedia cells inhibits both the discharge of spontaneous action potentials6 and secretion7,8. In addition, recent immunohistochemical studies in rats indicate that central neurones which apparently contain γ-aminobutyric acid (GABA) also project to the pars intermedia9,10. Here we report that in the same species GABA directly affects the electrophysiological properties of endocrine cells isolated from the pars intermedia and that the ionic and pharmacological characteristics of this action of GABA resemble those encountered at many GABAergic synapses in the central nervous system (CNS). We conclude that the brain can influence the endocrine cells of the pars intermedia directly through GABAergic mechanisms.
TL;DR: This chapter presents a short review of the advantages and drawbacks of the various markers available for GABAergic neurons and later presents findings of current study.
Abstract: Publisher Summary Within the conceptual framework of neurosecretion and of humoral hypothalamic control of adenohypophysis, numerous investigations have been carried out over the last decades aiming at: (a) the characterization and identification of the various hypophysiotropic factors secreted by the hypothalamus; (b) the understanding of the various mechanisms by which the release of neurosecretory substances could be regulated. That a neuroendocrine role could be played by gamma-aminobutyric acid (GABA), a recognized inhibitory transmitter in the central nervous system has been suggested by studies in which pharmacological manipulations of GABAergic transmission were accompanied by modification of various endocrine parameters. Even in the cases where consistent effects were reported, it still remains to be assessed whether these effects are physiologically meaningful or just represent a pharmacological curiosity. One way to provide another type of experimental data for GABAergic neuroendocrine regulation is to look for morphological evidence, i.e. to investigate whether or not GABAergic cells or terminals—here defined in a narrow sense as those that contain GABA markers—are actually localized at the presumed strategic sites for the suspected GABA-related controls. This chapter presents a short review of the advantages and drawbacks of the various markers available for GABAergic neurons and later presents findings of current study.
TL;DR: Data indicate that exiting GABA is cotransported with Na+.
Abstract: Presynaptic GABAergic nerve terminals accumulate gamma-aminobutyric acid (GABA) by a sodium-dependent carrier mechanism in which two Na+ are co-transported with one GABA. We have examined the influence of external GABA and cations on GABA efflux from 3H-GABA loaded rat brain synaptosomes, to determine whether or not the carriers can also mediate GABA efflux. We observed that, in Ca-free media (to minimize Ca-dependent, evoked release), external GABA promotes GABA efflux when the medium contains Na+, but inhibits GABA efflux in the absence of Na+. The efflux of GABA into Ca-free media is stimulated by depolarization (either with veratridine or increased external K+). These data, and published data on the internal Na+ dependence of GABA efflux into Ca-free media, indicate that exiting GABA is cotransported with Na+. The stimulatory effect of depolarization is consistent with efflux of Na+ along with the uncharged GABA. The (carrier-mediated) efflux is also stimulated when the carriers cycle inward with Na+ + GABA. The inhibitory effect of GABA in Na+-free media implies that GABA can bind to unloaded carriers and that the carriers loaded only with GABA cycle very slowly, if at all. Our data, and data from the literature, can be fitted to a simple model with sequential binding of solutes: external GABA binds to the carrier first, and only the free or fully-loaded (with 2Na+ + 1GABA) carriers can cycle. Other binding sequences and random binding, do not fit the experimental observations.
TL;DR: It is suggested that the aggressive responses exhibited by isolated DBA mice but not by isolated C57 mice may be related to lower levels of the inhibitory neurotransmitter in the olfactory bulb and striatum.
Abstract: In order to investigate the effects of social isolation on aggressive behavior and GABA levels in different brain areas, inbred mice of the C57 B1/6 and the DBA/2 strains were housed inidividually over a period of 8 weeks. Social isolation induced a clear increase of aggressive responses only in the DBA/2 strain and a decrease of GABA levels in septum, striatum, olfactory bulb and posterior colliculus in both the C57B1/6 and in the DBA/2 strains. An increase of neurotransmitter concentration was observed in amygdala of DBA mice. DBA mice when compared when compared to C57 mice showed significantly lower levels of GABA in olfactory bulb and striatum. These results are discussed in light of several previous studies which have pointed out a correlation between a deficiency of GABA mediated inhibition in some brain areas and different kinds of aggressive behavior as well as the possibility of blockade of aggressive behavior by potentiation of GABAergic mediated inhibition. A possible suggestion emerging from our results is that the aggressive responses exhibited by isolated DBA mice but not by isolated C57 mice may be related to lower levels of the inhibitory neurotransmitter in the olfactory bulb and striatum.
TL;DR: A highly significant positive correlation was found between seizure excitability and CSF GABA level, but not between CSF and plasma GABA concentrations.
Abstract: Various studies suggest that alterations in GABAergic function may be connected to epileptic seizures. Low CSF GABA levels have been reported in epilepsy and also febrile convulsions of children. In this study the pentet-razole seizure threshold of dogs was compared with the concentration of GABA in the CSF and blood plasma. A highly significant positive correlation was found between seizure excitability and CSF GABA level, but not between CSF and plasma GABA concentrations.
TL;DR: Analysis of free GABA in CSF does not appear useful for diagnosis of suspected Huntington's chorea, nor as a possible predictive test for persons genetically at risk for Huntington’s chorea.
Abstract: gamma-Aminobutyric acid (GABA) concentrations were measured in CSF specimens from two large groups of control subjects, one without neurological or psychiatric disease, and one with a variety of neurological disorders not known to involve altered GABAergic function in brain. CSF GABA was also measured in patients with Huntington's chorea and in patients with other choreiform disorders. GABA was measured in CSF by a modification of the ion exchange-fluorometric method that featured use of a relatively large cation exchange column, and a markedly decreased quantity of sulfosalicylic acid for deproteinization of CSF. Mean BABA concentrations in CSF were 87 and 77 nmol/liter for neurologically normal and abnormal control subjects, 82 nmol/liter for the Huntington's chorea patients, and 105 nmol/liter for patients with other forms of chorea. The mean concentration of homocarnosine was not reduced in CSF of Huntington's chorea patients as compared with controls. Mean CSF GABA concentrations found in control subjects were less than half the lowest control means previously reported. These low values are attributable in part to a reduction in on-column hydrolysis of conjugated forms of GABA in CSF, which can be produced by excessive sulfosalicylic acid, and in part to improved chromatographic resolution of GABA from other unknown o-phthalaldehyde-reactive compounds in CSF. Analysis of free GABA in CSF does not appear useful for diagnosis of suspected Huntington's chorea, nor as a possible predictive test for persons genetically at risk for Huntington's chorea.
TL;DR: Data agree with previous findings indicating a GABA-antagonistic effect of naloxone, and support the hypothesis that the anticonvulsant effect of morphine might be, at least in part, due to an increase in GABAergic activity at the synaptic level.
TL;DR: By the authors' criteria, putative GABAergic and glycinergic amacrine cells are mature between postnatal day 10 (P10) and P12, around the time when the eyes first open and direction-selective ganglion cells can first be recorded.
Abstract: The main findings from our studies on the emergence and maturation of neurotransmitter systems in the rabbit retina are that, during normal development: (1) the commitments for certain neurons to become GABAergic, glycinergic, or dopaminergic are made prenatally; the maturation of these neurons, however, occurs postnatally; (2) specific accumulations of exogenously supplied transmitters by presumed retinal neurons were first observed autoradiographically around embryonic day 22 (E22) for gamma-aminobutyric acid (GABA), E25 for glycine, and E27 for dopamine, suggesting that putative GABAergic, glycinergic, and dopaminergic neurons are determined phenotypically at least by these days; (3) based upon the three transmitter-specific properties--uptake, synthesis, and release--the uptake property is generally the first to emerge, while the appearance of the other properties follows a precise and distinct temporal pattern for each of the transmitters studied; (4) for GABAergic and glycinergic systems, the emergence of K+-stimulated, Ca2+-dependent release mechanisms occurs many days after the first appearance of the uptake properties; in contrast, the mechanisms for dopamine uptake and release emerge at about the same time; and (5) by our criteria, putative GABAergic and glycinergic amacrine cells are mature between postnatal day 10 (P10) and P12, around the time when the eyes first open and direction-selective ganglion cells can first be recorded; however, the dopaminergic neurons probably are not mature until about P24.
TL;DR: The magnitudes and distribution of in vivo cerebral metabolic responses to specific GABA agonists and antagonists were not correlated simply with markers for GABAergic synapses, which indicates that additional factors, such as neural circuitry, regulate the LCGU responses to GABAergic drugs.
Abstract: The [14C]2-deoxy-D-glucose method of Sokoloff et al. (Sokoloff, L., M. Reivich, C. Kennedy, M.H. Des Rosiers, C. S. Patlak, K. D. Pettigrew, O. Sakurada, and M. Shinohara (1977) J. Neurochem. 28:897-916) weas used to study local cerebral glucose utilization (LCGU) in rats treated with gamma-aminobutyric acid (GABA) agonist (muscimol and 4,5,6,7-tetrahydroisoxazolo[5,4-C]pyridin-3-ol, THIP) and antagonist (bicuculline) drugs. It was of interest to determine if the pattern of LCGU responses to GABA agonists and antagonists administered systemically in vivo would reflect the known distributions of markers for central GABAergic synapses. The patterns of LCGU responses to muscimol and THIP generally were similar. Most brain regions showed dose-dependent decreases in LCGU; others showed no effects; but the red nucleus showed an increase. The GABA antagonist bicuculline produced convulsions and variable LCGU responses, depending on the time of administration. Bicuculline also partially antagonized the depressant effects of muscimol of LCGU. The magnitudes and distribution of in vivo cerebral metabolic responses to specific GABA agonists were not correlated simply with markers for GABAergic synapses. This lack of correlation indicates that additional factors, such as neural circuitry, regulate the LCGU responses to GABAergic drugs.
TL;DR: The push-pull cannula technique was used to examine the endogenous release of GABA from the medial preoptic area (MPO) of unanesthetized rats and indicated that endogenous GABA release in OVX animals was only 60–70% of that in diestrous animals.
Abstract: The push-pull cannula technique was used to examine the endogenous release of GABA from the medial preoptic area (MPO) of unanesthetized rats. In diestrous females the mean resting release of GABA was 27.1±2.0 pmol/min. GABA release was significantly elevated by increasing the potassium concentration in the perfusion solution to 50 mM, whereas it was dramatically inhibited by mercaptoproprionic acid (1.0 mM), a glutamic acid decarboxylase inhibitor. A comparison between diestrous females and chronically castrated animals indicated that endogenous GABA release in OVX animals was only 60–70% of that in diestrous animals. A model for the presynaptic inhibition of NE by estrogen receptive GABAergic neurons in the MPO is proposed.
TL;DR: Data seem to demonstrate that pharmacological enhancement of endogenous GABAergic tone is followed by inhibition of PRL secretion and suggest that GABA may exert an inhibitory control on PRL release in humans.
Abstract: To find out whether the gamma-aminobutyric acid (GABA)ergic system affects PRL secretion in humans, sodium valproate (DPA or Na-dipropyl-acetate), a drug inducing increase of endogenous GABA, was administered to 20 normal and 15 hyperprolactinemic subjects. PRL circulating levels were measured by RIA in the samples obtained after acute oral treatment with 400 mg DPA. A significant decrease (P less than 0.01) in comparison with basal levels was observed in normal women from 30-180 min after drug administration. DPA treatment also lowered blood PRL levels in hyperprolactinemic subjects (seven females) without evidence of pituitary tumor. A decrease very similar to the one found in normal subjects (P less than 0.05 vs. basal levels) was observed within 180 min from drug ingestion. Conversely, no significant changes were found after the same treatment in hyperprolactinemic patients with evidence of prolactinoma (seven females and one male). Taken together, these data seem to demonstrate that pharmacological enhancement of endogenous GABAergic tone is followed by inhibition of PRL secretion. They also suggest that GABA may exert an inhibitory control on PRL release in humans. In hyperprolactinemic subjects, this GABAergic control appears to be present only when a pituitary tumor cannot be demonstrated.
TL;DR: It is hypothesized that the noradrenergic input to the area dentata increases the efficacy of extrinsic afferents while also facilitating recurrent granule cell inhibition mediated by GABAergic interneurons.
TL;DR: The influence of the intrapallidal application of GABA-related compounds on the release of Met-enkephalin in the globus pallidus and the caudate nucleus in the two hemispheres was investigated in vivo in the cat to suggest that GABAergic systems can contribute to some bilateral regulation of striato-pallidal enkphalinergic neurones.
TL;DR: The findings indicate that GABA-mediated inhibition involves both dopaminergic and non-dopaminergic neurones within the VTA, and possible implications for human pathology are discussed.
Abstract: The spontaneous activity of rats was measured after activation or inhibition of GABA activity in the ventral tegmental area of the midbrain (VTA). Six hours after bilateral injection of ethanolamine-o-sulphate (GABA agonist) into the VTA, the behavioural activation induced either by d-amphetamine (amph) or by bilateral VTA infusion of a long-lasting enkephalin analogue was completely blocked. Bilateral infusion of picrotoxin (GABA antagonist) into the VTA elicited a short-lived (40 min) dose-dependent behavioural activation which was not reduced either by prior specific lesion of the meso-cortico-limbic dopaminergic neurones or by administration of the opiate antagonist naloxone. Moreover, the simultaneous administration of picrotoxin and amph induced complex changes in behaviour which consisted of additive effects during the first 40 min, followed by an inhibition of the activating effect of amph. Our findings indicate that GABA-mediated inhibition involves both dopaminergic and non-dopaminergic neurones within the VTA, and possible implications for human pathology are discussed.
TL;DR: Evaluation of the data from homogeneous subgroups of this population disclosed that both the propensity of lumbar CSF GABA levels to decrease with age and the magnitude of the rostrocaudal GABA concentration gradient are more pronounced in females, suggesting possible neuroendocrine involvement.
Abstract: • Central nervous system γ-aminobutyric acid (GABA) activity was demonstrated to be an age- and sex-dependent phenomenon through the study of GABA concentration in lumbar CSF obtained from 87 drug-free normal individuals. Evaluation of the data from homogeneous subgroups of this population disclosed that both the propensity of lumbar CSF GABA levels to decrease with age and the magnitude of the rostrocaudal GABA concentration gradient are more pronounced in females, suggesting possible neuroendocrine involvement. Thus, age and sex are important variables that normally influence central GABAergic activity. Patient populations included in clinical investigations must be age- and sex-matched to avoid invalid conclusions biased by these physiologic variations in CSF GABA concentrations.
TL;DR: It seems that GABA autoreceptors are not functionally coupled to benzodiazepine receptors in rat cerebral cortex, as inhibition of release was prevented by the GABA antagonists bicuculline and picrotoxin.
Abstract: Depolarization-induced release of [3H]gamma-aminobutyric acid ([3H]-GABA) from preloaded slices of rat cerebral cortex was inhibited by muscimol and THIP in a dose-dependent fashion. This inhibition of release was prevented by the GABA antagonists bicuculline and picrotoxin. These results confirm previous reports postulating the existence of GABA autoreceptors on GABAergic terminals. Since benzodiazepines are known to facilitate post-synaptic GABA actions, the effect of flunitrazepam on the inhibition of GABA release mediated through the autoreceptors has been examined. At a concentration of 1 microM or 10 microM, flunitrazepam had no effect on the IC50 values for muscimol or THIP in inhibiting stimulated GABA release. It thus seems that GABA autoreceptors are not functionally coupled to benzodiazepine receptors in rat cerebral cortex.