Gabaergic processes involved in the control of dopamine release from nigrostriatal dopaminergic neurons in the cat

Abstract

Push-pull cannulae were used to study the release of 3H-dopamine ( 3H-DA) continuosly synthetized from L-3,5- 3H-tyrosine in the caudate nucleus and the substantia nigra of the “encéphale isolé” cat. GABA (10 −5M), muscimol (10 −6 M), γ-hydroxybutyrate (GHB, 10 −5 M), GABA-choline (GABA-CH, 10 −5 M) and amino-oxyacetic acid (AOAA, 10 −5 M) stimulated the release of 3H-DA in the caudate nucleus when introduced for 15 min in the superfusing medium. The initial stimulation of 3H-DA release was followed by an inhibition of transmitter release when GABA was introduced for a longer time (60 min) into the caudate nucleus. GABA (10 −5 M) had no effect on the release of 3H-DA in the substantia nigra. However, muscimol (10 −6 M), GHB (10 −5 M) and baclofen (10 −6 M) stimulated the dendritic release of 3H-DA when each was introduced for 15 min in the substantia nigra. The introduction for 15 min of GABA (10 −5 M), muscimol (10 −6 M), GHB (10 −5 M), GABA-Ch (10 −5 M) or baclofen (10 −6 M) into the substantia nigra simultaneously induced a stimulation of 3H-DA release in the ipsilateral caudate nucleus. A marked post stimulatory effect was seen with muscimol. When GABA (10 −5 M) was applied for 75 min into the substantia nigra, the initial stimulation of 3H-DA release (30 min) seen in the caudate nucleus was followed by a short-lasting inhibitory phase (15 min). This inhibition of 3H-DA release was followed by a second stimulation period. This multiphasic phenomenon was not seen with other compounds. The stimulation of 3H-DA release in the caudate nucleus induced by a 15 min nigral application of GABA (10 −5 M) was no longer seen when picrotoxin (10 −5 M) was added with GABA in the substantia nigra. On the basis of these results it is proposed that at least two types of GABAergic regulatory processes are involved in the control of the activity of the dopaminergic neurons in the substantia nigra. On the other hand, the interaction of GABA or GABA-related compounds with GABAergic receptors in the striatum may facilitate DA release from dopaminergic terminals through an intrastriatal interneuronal process. The secondary inhibition of 3H-DA release induced by GABA or GHB could be mediated by a non-GABAergic striato-nigral pathway.