Effects Of GABA Receptor Agonists Research Articles

Effects of GABA receptor agonists on [ 3H]dopamine release from median eminence and pituitary neurointermediate lobe

The effects of GABA A and GABA B receptor agonists were examined on stimulus-induced release of [ 3H]dopamine ([ 3H]DA) from a synaptosomal preparation of median eminence (ME) and pituitary neurointermediate lobe (NI). Muscimol was found to inhibit [ 3H]DA release from ME in a bicuculline-sensitive, strychnine-insensitive manner, but had no effect in NI. Homocarnosine also inhibited [ 3H]DA release from ME. Baclofen had no effect in either area. These results demonstrate an interaction between two putative prolactin release inhibitory factors, DA and GABA, at the site of secretion into hypophysial portal blood.

GABA receptor agonists: pharmacological spectrum and therapeutic actions.

From the data discussed in this review it appears that GABA receptor agonists exhibit a variety of actions in the central nervous system, some of which are therapeutically useful (Table V). GABA receptor agonists, by changing the firing rate of the corresponding neurons accelerate noradrenaline turnover without changes in postsynaptic receptor density and diminish serotonin liberation with an up-regulation of 5HT2 receptors. These effects differ from those of tricyclic antidepressants which primarily block monoamine re-uptake and cause down-regulation of beta-adrenergic and 5HT2 receptors. The GABA receptor agonist progabide has been shown to exert an antidepressant action which is indistinguishable from that of imipramine in patients with major affective disorders. The fact that: (a) GABA receptor agonists and tricyclic antidepressants affect noradrenergic and serotonergic transmission differently; and (b) tricyclic antidepressants alter GABA-related parameters challenges the classical monoamine hypothesis of depression and suggests that GABA-mediated mechanisms play a role in mood disorders. Decreases in cellular excitability produced by GABAergic stimulation leads to control of seizures in practically all animal models of epilepsy. GABA receptor agonists have a wide spectrum as they antagonize not only seizures which are dependent on decreased GABA synaptic activity but also convulsant states which are apparently independent of alterations in GABA-mediated events. These results in animals are confirmed in a wide range of human epileptic syndromes. GABA receptor agonists decrease dopamine turnover in the basal ganglia and antagonize neuroleptic-induced increase in dopamine release. On repeated treatment, progabide prevents or reverses the neuroleptic-induced up-regulation of dopamine receptors in the rat striatum and antagonizes the concomitant supersensitivity to dopaminomimetics. Behaviorally, GABA receptor agonists diminish the stereotypies induced by apomorphine or L-DOPA suggesting that GABAergic stimulation results also in an antidopaminergic action which is exerted beyond the dopamine synapse. These effects of GABA receptor agonists may represent the basis of the antidyskinetic action of these compounds which, however, remains to be fully confirmed. GABA receptor agonists reduce striatal acetylcholine turnover, an effect which occurs at doses much lower than those which affect dopamine neurons. Since hyperactivity of cholinergic neurons plays a determinant role in the pathogenesis of some parkinsonian symptoms, it is conceivable that GABAergic stimulation is effective in ameliorating Parkinson's disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of GABA receptor agonists on [ 3H] flunitrazepam binding to rat cerebellar and hippocampal membranes

The effects of GABA agonists on [ 3H] flunitrazepam binding were examined in membranes from CNS areas proposed to contain different populations of benzodiazepine binding site subtypes ( BZ 1 BZ 2 ). Since these effects were broadly similar in both cerebellar and hippocampal membranes, it seems unlikely that GABA receptors interacting with the proposed BZ 1 BZ 2 binding sites haue markedly different properties. Sodium chloride clearly facilitated the potentiating effect of muscimol on [ 3H] flunitrazepam binding but produced a complex interaction uith the effects of GABA itself and the partial agonist imidazoleacetic acid in the phosphate buffer system used.

Differential influence of GABA-ergic agents on dopamine metabolism in extrapyramidal and limbic systems of the rat

The effect of GABA receptor agonists (muscimol, SL 76002) and GABA transaminase inhibitors (e.g. dipropylacetamide) on dopamine (DA) metabolism has been investigated in striatum and limbic areas of the rat. SL 76002, muscimol and dipropylacetamide decrease the rate of DA disappearance after α-methyl-p-tyrosine in striatum but not in limbic areas (nucleus accumbens+olfactory tubercle). Moreover, SL 76002 and muscimol reduce more markedly in striatum than in limbic areas the synthesis of DA as estimated from the in vivo accumulation of DOPA following inhibition of dopadecarboxylase or the in vitro formation of 14CO 2 from 1- 14C-tyrosine (in slices). However, SL 76002 and muscimol counteract in a dose-dependent manner haloperidol-induced increase in DA utilization and in tyrosine hydroxylase activity in both striatum and limbic areas, this effect being more pronounced in the former region. These findings indicate that GABA mimetic agents affect more markedly striatal than limbic DA neurons suggesting a more effective GABA-ergic influence on the extrapyramidal than on the limbic DA systems.