GABA(B)-RECEPTOR ACTIVATION ALTERS THE FIRING PATTERN OF DOPAMINE NEURONS IN THE RAT SUBSTANTIA-NIGRA

Previous electrophysiological experiments have emphasized the importan ce of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to co nstitute an important modulatory control mechanism. In the present stu dy, extracellular recording techniques were used to investigate the si gnificance of GABA(B)-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous admin istration of the GABA(B)-receptor agonist baclofen (1-16 mg/kg) was as sociated with a dose-dependent regularisation of the firing pattern, c oncomitant 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 fir ing pattern of nigral DA neurons, including a reduction of burst firin g. Both the regularisation of the firing pattern and inhibition of fir ing rate produced by systemic baclofen administration was antagonized by the GABA(B)-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GA BA(A)-receptor agonist muscimol produced effects on the firing propert ies of DA neurons that were opposite to those observed following baclo fen, i.e., an increase in firing rate accompanied by a decreased regul arity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produ ced a moderate, dose-dependent increase in the firing rate of the nigr al DA neurons as well as a slightly regularized firing pattern. Pretre atment 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 fir ing rate on the nigral DA neurons produced by baclofen. The present re sults clearly show that GABA(B)-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously describe d ability of glutamate to induce burst firing activity on these neuron s. (c) 1993 Wiley-Liss, Inc.