Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GABA Modulators”

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 1,351 records · Page 75Linked to original sources
PubMed1997

Phenobarbital and 3-methylcholanthrene treatment alters phase I and II enzymes and the sensitivity of the rat colon to the carcinogenic activity of azoxymethane.

It has been hypothesized that cancer risk may be influenced by phase I and II drug-metabolizing enzyme systems. This study attempted to determine the relationship between colon phase I and II enzyme activity and the subsequent induction of aberrant crypt foci (ACF), preneoplastic lesions by azoxymethane (AOM), a colon-specific carcinogen. Phenobarbital (PB) and 3-methylcholanthrene (MC) treatment (prototype hepatic inducers of phase I and II enzymes) provided the framework to study the induction of phase I and II enzymes in the rat colonic mucosa. Following induction for five consecutive days, the animals were given a single injection of AOM. Phase I and II enzymes were determined fluorometrically and spectrophotometrically and ACF were identified microscopically. Phase I and II xenobiotic metabolizing enzymes were induced in the rat colonic mucosa by prototype hepatic inducers. A lower number of ACF and crypt multiplicity was observed in animals induced with MC than in those in the non-induced and PB groups. Altered levels of phase I and II enzymes in the colon during preinitiation stages were associated with modulation in the growth of ACF, putative preneoplastic lesions.

Animals↗
PubMed1998

Alterations in GABAA receptor alpha 1 and alpha 4 subunit mRNA levels in thalamic relay nuclei following absence-like seizures in rats.

Modification of GABAA receptor mRNA levels by seizure activity can regulate general neuronal excitability. The possibility of absence seizure-induced alteration in GABAA receptor alpha 1, alpha 4, beta 2, and gamma 2 subunit gene expression in thalamic relay nuclei was studied in a rat model of absence seizures induced by gamma-hydroxybutyric acid (GHB). We observed a marked increase in alpha 1 mRNA and a corresponding decrease in alpha 4 mRNA in thalamic relay nuclei 2-4 h after the onset of GHB-induced absence seizures (when the seizures were terminating). These changes were selective to these alpha isoforms as neither beta 2 nor gamma 2 mRNA changed following seizures and occurred only in thalamic relay nuclei but not in hippocampus, a structure from which absence seizures do not evolve. The alterations in alpha 1 and alpha 4 mRNA persisted until about 12 h, and by 24 h after the seizure-onset the mRNA levels normalized. Blocking GHB-seizures produced no change in the levels of alpha 1 and alpha 4 mRNA in thalamic relay nuclei, suggesting that seizures themselves were responsible for mRNA alterations. In order to determine if absence seizure-induced changes in alpha 1 and alpha 4 mRNA had any physiological significance, GHB was readministered in rats 6 and 24 h after the onset of seizures. The total duration of GHB-seizures was found to be significantly decreased when GHB was readministered at 6 h but not 24 h after the seizure-onset. These results suggest that absence seizures regulate GABAA receptor alpha 1 and alpha 4 gene expression in thalamic relay nuclei as a compensatory mechanism by which absence seizures are terminated.

4-Butyrolactone↗
PubMed1995

Interaction of the beta-carboline harmaline with a GABA-benzodiazepine mechanism: an electrophysiological investigation on rat hippocampal slices.

An interaction of harmaline (HA), a beta-carboline, with benzodiazepine (Bzd) receptors, has been reported. HA perfusion induced a similar, although less potent, depressing effect as clonazepam (CLO) on the amplitude of the population spikes (PS) evoked by Schaffer collateral stimulation in the CA1 area of rat hippocampal slices. The suppressant effect of both CLO and HA on PS amplitude was reversed by simultaneous perfusion of the GABA antagonist picrotoxin. These results suggest that HA acts as a weak or partial agonist at Bzd receptors.

Action Potentials↗
PubMed1996

Down-regulation of the GABA receptor subunits mRNA levels in mammalian cultured cortical neurons following chronic neurosteroid treatment.

We have recently shown that chronic neurosteroid, 5 alpha 3 alpha, treatment produced down-regulation of the GABA receptor binding and function, and heterologous uncoupling on the GABAA receptor complex in cultured mammalian cortical neurons. In order to explore the underlying mechanism of these observed down-regulation and heterologous uncoupling phenomenon, we investigated the effect of chronic 5 alpha 3 alpha (1 microM; 5 days) treatment on the GABAA receptor subunits mRNA levels, using RNase protection assay. We found that chronic neurosteroid, 5 alpha 3 alpha, treatment decreased the beta- and alpha-subunits mRNA levels while not altering the gamma 2S-subunit mRNA levels in the cortical neurons. The decrease in the beta-subunits mRNA levels suggests a decrease in the presence of the beta-subunits in the composition of GABAA receptors. This phenomenon may explain the down-regulation of the GABAA receptor binding and function. A decrease in the alpha 3-subunit mRNA level suggests a corresponding decrease in the alpha 3-subunit in the composition of GABAA receptor isoforms, relative to other isoforms. This observation may be responsible for the chronic neurosteroid-induced uncoupling and decreased efficacy. In summary, chronic 5 alpha 3 alpha treatment produced down-regulation of the GABAA receptor beta- and alpha-subunit mRNA levels, and these changes may be associated with the down-regulation, heterologous uncoupling, and decreased efficacy of GABAA receptor complex in the cultured mammalian cortical neurons.

Amino Acid Isomerases↗
PubMed1995

The enhancement of muscimol-stimulated 36C1 influx by the antispastic 5-aryl-3-(alkylsulfonyl)-4H-1,2,4-triazole (MDL 27,531) in rat brain membrane vesicles.

The antispastic triazole, 4-methyl-3-methylsulphonyl-5-phenyl-4H-1,2,4-triazole (MDL 27,531) was tested in glycine- and muscimol-stimulated 36Cl- influx into brain membrane preparations. MDL 27,531 (100 nM) had no effect on glycine- (100 nM-400 microM) stimulated 36Cl- influx in brain stem tissue; on the other hand, MDL 27,531 (10 nM-10 microM) enhanced muscimol- (1 microM) stimulated 36Cl- influx in cerebellar but not cortical membranes. In the presence of the benzodiazepine (BZD) antagonist, flumazenil (10 microM), MDL 27,531 inhibited muscimol-stimulated flux. These data suggest a novel interaction of this triazole with subtypes of the gamma-aminobutyric acid (GABA)A receptor complex and the BZD receptor.

Animals↗
PubMed2003

Testosterone treatment induces behavioral disinhibition in adult male rats.

The importance of testosterone for impulsive-like behavior is unclear. Here we studied the effect of testosterone administration during 6 and 14 days (separate experiments) with one, three and five testosterone-filled silastic capsules implanted subcutaneously on shock-induced behavioral inhibition and on flunitrazepam-induced disinhibition in a modified Vogel's drinking conflict model in rats. Alleviation of shock-induced behavioral inhibition has been suggested to reflect impulsive-like behavior and/or anxiolysis. Treatment with the highest testosterone dose used for 6 (Experiment 1) and 14 (Experiment 3) days increased the number of shocks accepted. Testosterone treatment affected serum levels of testosterone and accessory sex organ weights. Flunitrazepam induced behavioral disinhibition in both testosterone-treated (for 14 days) and sham-treated rats. Moreover, testosterone treatment for 14 days resulted in enhanced GABA-induced 36Cl- uptake into synaptoneurosomes as compared to controls. In conclusion, testosterone produces behavioral disinhibition and may enhance brain GABAA receptor function.

Androgens↗
PubMed2006

GABA increases both the conductance and mean open time of recombinant GABAA channels co-expressed with GABARAP.

The single channel properties of recombinant gamma-aminobutyric acid type A (GABA(A))alphabetagamma receptors co-expressed with the trafficking protein GABARAP were investigated using membrane patches in the outside-out patch clamp configuration from transiently transfected L929 cells. In control cells expressing alphabetagamma receptors alone, GABA activated single channels whose main conductance was 30 picosiemens (pS) with a subconductance state of 20 pS, and increasing the GABA concentration did not alter their conductance. In contrast, when GABA(A) receptors were co-expressed with GABARAP, the GABA-activated single channels displayed multiple, high conductances (> or =40 pS), and GABA (> or =10 microM) was able to increase their conductance, up to a maximum of 60 pS. The mean open time of GABA-activated channels in control cells expressing alphabetagamma receptors alone was 2.3 +/- 0.1 ms for the main 30-pS channel and shorter for the subconductance state (20 pS, 0.8 +/- 0.1 ms). Similar values were measured for the 30- and 20-pS channels active in patches from cells co-expressing GABARAP. However higher conductance channels (> or =40 pS) remained open longer, irrespective of whether GABA or GABA plus diazepam activated them. Plotting mean open times against mean conductances revealed a linear relationship between these two parameters. Since high GABA concentrations increase both the maximum single channel conductance and mean open time of GABA(A) channels co-expressed with GABARAP, trafficking processes must influence ion channel properties. This suggests that the organization of extrasynaptic GABA(A) receptors may provide a range of distinct inhibitory currents in the brain and, further, provide differential drug responses.

Animals↗
PubMed1999

Blockade of glutamate receptors and barbiturate anesthesia: increased sensitivity to pentobarbital-induced anesthesia despite reduced inhibition of AMPA receptors in GluR2 null mutant mice.

BACKGROUND: Barbiturates enhance gamma-aminobutyric acid type A (GABA(A)) receptor function and also inhibit the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptor. The relative contribution of these actions to the behavioral properties of barbiturates is not certain. Because AMPA receptor complexes that lack the GluR2 subunit are relatively insensitive to pentobarbital inhibition, GluR2 null mutant mice provide a novel tool to investigate the importance of AMPA receptor inhibition to the anesthetic effects of barbiturates. METHODS: GluR2 null allele (-/-), heterozygous (+/-), and wild-type (+/+) mice were injected with pentobarbital (30 and 35 mg/kg intraperitoneally). Sensitivity to anesthetics was assessed by measuring the latency to loss of righting reflex, sleep time, and the loss of corneal, pineal, and toe-pinch withdrawal reflexes. In addition, patch-clamp recordings of acutely dissociated CA1 hippocampal pyramidal neurons from (-/-) and (+/+) mice were undertaken to investigate the effects of barbiturates on kainate-activated AMPA receptors and GABA-activated GABA(A) receptors. RESULTS: Behavioral tests indicate that sensitivity to pentobarbital was increased in (-/-) mice. In contrast, AMPA receptors from (-/-) neurons were less sensitive to inhibition by pentobarbital (concentrations that produced 50% of the maximal inhibition [IC50], 301 vs. 51 microM), thiopental (IC50, 153 vs. 34 microM), and phenobarbital (IC50, 930 vs. 205 microM) compared with wild-type controls, respectively. In addition, the potency of kainate was greater in (-/-) neurons, whereas no differences were observed for the potentiation of GABA(A) receptors by pentobarbital. CONCLUSIONS: The GluR2 null mutant mice were more sensitive to pentobarbital anesthesia despite a reduced sensitivity of GluR2-deficient AMPA receptors to barbiturate blockade. Our results indicate that the inhibition of AMPA receptors does not correlate with the anesthetic effects of barbiturates in this animal model. We postulate that the increase in the sensitivity to anesthetics results from a global suppression of excitatory neurotransmission in GluR2-deficient mice.

Alleles↗
PubMed2005

Influence of the point mutation alpha-1-H101R on the assembly of gamma-aminobutyric acid type A receptors.

The point mutation H101R in the alpha1-subunit of gamma-aminobutyric acid type A receptors is known to abolish effects by benzodiazepine diazepam. This mutation and homologous mutations in other alpha-subunits have been used to quantify receptor pentamers containing two different alpha-subunit isoforms, and to study the role of alpha-subunit isoforms in the response of mice to diazepam. Both types of study assumed implicitly or explicitly that this mutation strongly affects assembly with the gamma2-subunit. Here, we investigated the assembly properties of mutated in comparison with wild-type subunits, and demonstrate that alpha1H101R has similar assembly properties as wild-type alpha1.

Animals↗
PubMed2000

Postsynaptic receptor occupancy during evoked transmission at striatal GABAergic synapses in vitro.

The effect of benzodiazepines (BZs) on GABA(A)-ergic synaptic responses depends on the control receptor occupancy: the BZ-induced enhancement of receptor affinity can lead to greater peak amplitudes of quantal responses only when, under normal conditions, receptors are not fully saturated at peak. Based on this fact, receptor occupancy at the peak of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) has been assessed in various mammalian neuronal preparations. To use the same principle with compound (or multiquantal), action potential-evoked IPSCs, complications introduced by quantal asynchrony in conjunction with the BZ-induced increase in the decay time of the quantal responses have to be overcome. We used a simple analytic convolution model to calculate expected changes in the rise time and amplitude of postsynaptic currents when the decay time constant, but not the peak amplitude, of the underlying quantal responses is increased, this being the expected BZ effect at saturated synapses. Predictions obtained were compared with the effect of the BZ flunitrazepam on IPSCs recorded in paired pre- and postsynaptic whole cell voltage-clamp experiments on striatal neurons in cell culture. In 22 pairs, flunitrazepam (500 nM) reliably prolonged the decay of IPSCs (49 +/- 19%, mean +/- SE) and in 18 of 22 cases produced an enhancement in their peak amplitude that varied markedly between 3 and 77% of control (26.0 +/- 5.3%). The corresponding change in rise time, however (+0.38 +/- 0.11 ms, range -0.8 to +1.3 ms) was far smaller than calculated for the observed changes in peak amplitude assuming fixed quantal size. Because therefore an increase in quantal size is required to explain our findings, postsynaptic GABA(A) receptors were most likely not saturated during impulse-evoked transmission at these unitary connections. The peak amplitudes of miniature IPSCs in these neurons were also increased by flunitrazepam (500 nM, +26.8 +/- 6.6%), and their decay time constant was increased by 26.3 +/- 7.3%. Using these values in our model led to a slight overestimate of the change in compound IPSC amplitude (+28 to +30%).

Animals↗
PubMed2001

Effect of prenatal exposure to diazepam on brain GABA(A) receptor mRNA levels in rats examined at late fetal or adult ages.

This study tested the hypotheses that in utero exposure to diazepam (DZ): (1) exerts long-lasting effects on GABA(A) receptor function by altering GABA(A) receptor subunit mRNA levels in specific brain regions of adult animals and/or (2) alters GABA(A) subunit mRNA expression in exposed fetuses. We assayed levels of mRNAs encoding several of the most predominant GABA(A) receptor subunits as well as cyclophilin mRNA. Analysis of mRNA levels in the cortex in adults showed that only gamma2S mRNA levels varied significantly with prenatal drug exposure, an effect unrelated to DZ action to the GABA(A) receptor. Analysis in fetuses indicated that mRNA levels varied as a function of both fetal sex and fetal drug environment. Irrespective of sex, DZ exposure increased both alpha1 and cyclophilin mRNAs in fetal brainstem whereas the mRNA levels of gamma2S were increased and decreased, respectively, in the telencephalon and hypothalamus of DZ-exposed fetuses.

Age Factors↗
PubMed2002

Gamma-aminobutyric acidA and benzodiazepine receptor alterations in the rat brain after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle.

Gamma-aminobutyric acidA (GABA(A)) and benzodiazepine (BZ) receptors and dopamine uptake sites in 6-hydroxydopamine-treated rat brains were studied by receptor autoradiography using [3H]muscimol, [3H]flunitrazepam and [3H]mazindol binding, respectively. The rats were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks post-lesion. Degeneration of the nigrostriatal pathway after 6-hydroxydopamine treatment caused a significant loss of dopamine uptake sites in the ipsilateral striatum and substantia nigra (SN) in the lesioned animals. In the contralateral side, however, dopamine uptake sites showed no significant changes in the brain throughout the experiments. On the other hand, no significant changes in GABA(A) receptors were observed in the brain of both the ipsilateral and contralateral sides during post-lesion. In contrast, BZ receptors were observed significantly increased in the ventromedial part of striatum of the ipsilateral side from 2 to 4 weeks post-lesion. Furthermore, a transient increase in BZ receptors was found in the ipsilateral SN only at 2 weeks post-lesion. In contralateral side, most regions examined showed no significant changes in BZ receptors throughout the experiments except for a transient increase in the SN at 1 week post-lesion. These results demonstrate that 6-hydroxydopamine can cause severe functional damage in dopamine uptake sites in the nigrostriatal pathway. Our results also suggest that the change in BZ receptors is more pronounced than that in GABA(A) receptors in the brain after 6-hydroxydopamine treatment. Furthermore, our findings suggest that the increase in BZ receptors in the brain of 6-hydroxydopamine-treated model may be due to the additional disruption of the nigrostriatal dopamine system. Thus, investigations into possible changes in neurotransmitter receptors other than dopaminergic receptors appear to be important for the elucidation of pathogenesis of Parkinsons disease.

Animals↗
PubMed2000

Acute effects of zopiclone on blood glucose level and serum lipids in hyperlipidemic rats. Interactions with PK 11195 and flumazenil.

UNLABELLED: Intraperitoneal administration of 5 mg/kg zopiclone a cyclopyrolone acting on the central benzodiazepine receptors was found to produce significant reduction of total lipids, total cholesterol and triglyceride in rats randered hyperlipidemic by intraperitoneal injection of Triton W-1339. Blood glucose level was also reduced. Flumazenil (10 mg/kg) potentiated the hypoglicemic effect of zopiclone but had no additional effect on serum lipids. PK 11195 (25 mg/kg) antagonized the hypolipidemic effects of zopiclone. IN CONCLUSION: 1. The central benzodiazepine receptors are not involved in the hypolipidemic activity of zopiclone. 2. The peripheral type benzodiazepine receptors are partly responsible, for the hypolipidemic activity of this cyclopirrolone. 3. The changes of blood glucose level induced by these drugs does not seem to be related to benzodiazepine receptors.

Animals↗
PubMed2004

Evidence for participation of GABA(A) receptors in a rat model of secondary hyperalgesia.

We investigated the involvement of endogenous gamma-aminobutyric acid (GABA) in the modulation of secondary hyperalgesia induced by intraplantar (i.pl.) injection of 5% formalin in the rat tail-flick test. Intraplantar injection of gabamimetic drugs such as gabapentin (150-600 microg/site) or phenobarbital (20-80 microg/site) reversed secondary hyperalgesia, as measured by an increase in the tail-flick latency, thus displaying a peripheral antihyperalgesic effect. Central inhibition of the secondary hyperalgesia response by gabapentin was obtained following injection of either 200 microg intrathecally (i.t.) or 50 mg intraperitoneally (i.p.). The effects induced by gabamimetics were blocked locally or centrally by prior treatment with the specific GABA(A) receptor antagonist, bicuculline (80 ng/paw or 20 ng, i.t.). These data indicate the participation of endogenous GABA in the modulation of secondary hyperalgesia, through either a peripheral and/or a central action. They also indicate that GABA(A) receptors might be involved since a specific antagonist of these receptors (bicuculline) blocked this response.

Animals↗
PubMed2005

GABAergic modulation mediates antinociception produced by serotonin applied into thalamic nucleus submedius of the rat.

Our previous studies have indicated that the thalamic nucleus submedius (Sm) is involved in modulation of nociception as part of an ascending component of an endogenous analgesic system consisting of spinal cord-Sm-ventrolateral orbital cortex (VLO)-periaqueductal gray (PAG)-spinal cord loop and that microinjection of 5-hydroxytryptamine (5-HT) into Sm produces antinociception. The aim of the present study was to examine whether the gamma-aminobutyric acid (GABA)ergic modulation is involved in the Sm 5-HT-evoked antinociception. Experiments were carried out on lightly anesthetized rats with an implanted cannula targeting the Sm nucleus. The microinjection of GABA(A) receptor antagonist bicuculline dose-dependently depressed the tail flick (TF) reflex. A smaller dose (100 ng) of bicuculline enhanced the inhibition of TF reflex produced by 5-HT application into Sm, whereas application of GABA (2.5 microg) did not influence the TF reflex but significantly attenuated the 5-HT-evoked inhibition. These results indicate that GABA(A) receptor may be involved in mediating the 5-HT-induced antinociception in Sm possibly through a disinhibition mechanism.

Analysis of Variance↗
PubMed2001

The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities.

Steroids, synthesized in peripheral glands or centrally in the brain--the latter being named neurosteroids--exert an important role as modulators of the neuronal activity by interacting with different receptors or ion channels. In addition to the modulation of GABA(A), NMDA or cholinergic receptors, neuroactive steroids interact with an atypical intracellular receptor, the sigma(1) protein. This receptor has been cloned in several species, and highly selective synthetic ligands are available. At the cellular level, sigma1 agonists modulate intracellular calcium mobilization and extracellular calcium influx, NMDA-mediated responses, acetylcholine release, and alter monoaminergic systems. At the behavioral level, the sigma1 receptor is involved in learning and memory processes, the response to stress, depression, neuroprotection and pharmacodependence. Pregnenolone, dehydroepiandrosterone, and their sulfate esters behave as sigma1 agonists, while progesterone is a potent antagonist. This review will detail the physiopathological consequences of these interactions, focusing on recent results on memory and depression. The therapeutical interest of selective sigma1 receptor agonists in alleviating aging-related cognitive deficits will be discussed.

Animals↗
PubMed2001

GABAb receptors regulate chick retinal calcium waves.

Correlated spiking activity and associated Ca(2+) waves in the developing retina are important in determining the connectivity of the visual system. Here, we show that GABA, via GABA(B) receptors, regulates the temporal characteristics of Ca(2+) waves occurring before synapse formation in the embryonic chick retina. Blocking ionotropic GABA receptors did no affect these Ca(2+) transients. However, when these receptors were blocked, GABA abolished the transients, as did the GABA(B) agonist baclofen. The action of baclofen was prevented by the GABA(B) antagonist p-3-aminopropyl-p-diethoxymethyl phosphoric acid (CGP35348). CGP35348 alone increased the duration of the transients, showing that GABA(B) receptors are tonically activated by endogenous GABA. Blocking the GABA transporter GAT-1 with 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid (SKF89976A) reduced the frequency of the transients. This reduction was prevented by CGP35348 and thus resulted from activation of GABA(B) receptors by an increase in external [GABA]. The effect of GABA(B) receptor activation persisted in the presence of activators and blockers of the cAMP-PKA pathway. Immunocytochemistry showed GABA(B) receptors and GAT-1 transporters on ganglion and amacrine cells from the earliest times when Ca(2+) waves occur (embryonic day 8). Patch-clamp recordings showed that K(+) channels on ganglion cell layer neurons are not modulated by GABA(B) receptors, whereas Ca(2+) channels are; however, Ca(2+) channel blockade with omega-conotoxin-GVIA or nimodipine did not prevent Ca(2+) waves. Thus, the regulation of Ca(2+) waves by GABA(B) receptors occurs independently of N- and L-type Ca(2+) channels and does not involve K(+) channels of the ganglion cell layer. GABA(B) receptors are likely to be of key importance in regulating retinal development.

Animals↗
PubMed1997

Differential effects of neuroactive steroids on somatostatin and dopamine secretion from primary hypothalamic cell cultures.

This study investigated the effects of neuroactive steroids, which have been reported to modulate GABA-ergic transmission, on the secretion of somatostatin (SRIH) and also dopamine (DA) from primary rat hypothalamic cell cultures, where the release of both substances is regulated by a GABAA receptor-mediated inhibitory tone. Pregnenolone sulphate (PS), a negative allosteric modulator at the GABAA receptor, enhanced SRIH secretion in a time and dose-dependent manner (10(-12)-10(-8) M). This effect was reversed by muscimol (10(-8) M) and enhanced by bicuculline (10(-6) M), thus supporting an action of PS at the GABAA receptor. The release of endogenously synthesized dopamine (DA) was, however, unaffected by PS. A number of other steroids were also tested for their potential actions on SRIH and DA secretion. Allopregnanolone had slight but significant stimulatory actions on SRIH secretion, whereas tetrahydro-deoxycorticosterone (TH-DOC) markedly stimulated SRIH secretion with a bell-shaped dose response curve resembling that found for PS. The release of DA was unaffected by these neuroactive steroids but, unlike SRIH, DA release was stimulated by dehydroepiandrosterone sulphate (DHEAS). The results support the view that neuroactive steroids may play an important role in regulating some aspects of neuroendocrine function and they also provide the first demonstration of differential activities of neuroactive steroids within the hypothalamus at low, physiologically relevant concentrations. The results also raise the possibility that certain hypothalamic neuronal populations may possess uniquely different GABAA receptors and that such mechanisms may contribute to the functional development of the neuroendocrine system.

Animals↗