GABAB-Receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra

Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABA_B-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABA_B-receptor agonist baclofen (1–16 mg/kg) was associated with a dose-dependent regularisation of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16–32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularisation of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABA_B-receptor antagonist CGP 35348 (200 mg/kg, l.v.). The GABA_A-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a Cecreased regularity. The NMDA receptor antagonist MK 801 (0.4–3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3–10 min) did neither promote nor prevent the regularisation of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABA_B-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst Firing activity on these neurons. © 1993 Wiley-Liss, Inc.