GABA_B receptor-mediated modulation of the firing pattern of ventral tegmental area dopamine neurons in vivo

Abstract.

Previous work demonstrates the fundamental role of the firing pattern, specifically the burst firing mode of midbrain dopamine (DA) neurons in the regulation of DA release. Spontaneous burst firing has been shown to be dependent upon NMDA receptor activation of the DA cells. In addition to NMDA receptors, previous studies have reported that also GABA_B receptors modulate the firing pattern of DA neurons in the substantia nigra. In the present electrophysiological study the role of GABA_B receptors in the modulation of the firing pattern of DA neurons in the ventral tegmental area (VTA) in anaesthetised Sprague-Dawley rats was analysed. Systemic administration of the selective and potent GABA_B receptor agonist baclofen dose-dependently reduced firing rate and burst firing in VTA DA neurons. An increase in the regularity of DA cell firing was also observed. All these effects were effectively antagonized by administration of the selective GABA_B antagonist CGP 35348 (100 mg/kg or 200 mg/kg, i.v.). Administration of CGP 35348 (400 mg/kg, i.v.) per se was associated with a long-lasting increase in burst firing activity. The effects of systemic administration of baclofen, alone or in combination with CGP 35348, on the firing rate were largely mimicked by local microiontophoretic application of the drugs onto the DA neurons.

Our findings indicate that central GABA_B receptors may contribute to control of the burst firing mode of VTA DA neurons. Physiologically, activation of GABA_B receptors may subserve a dampening function on VTA DA cell excitability which may counterbalance NMDA receptor-mediated excitation.