Alpha‐1 adrenoreceptors modulate GABA release onto ventral tegmental area dopamine neurons

Abstract

The ventral tegmental area (VTA) plays an important role in reward and motivational processes involved in drug addiction. Previous studies have shown that alpha1‐adrenoreceptors (α1‐AR) are primarily found pre‐synaptically at this area. We hypothesized that GABA released onto VTA‐dopamine (DA) cells is modulated by pre‐synaptic α1‐AR. Recordings were obtained from putative VTA‐DA cells of male Sprague‐Dawley rats (28–50 days postnatal) using whole‐cell voltage clamp technique. Phenylephrine (10uM; α1‐AR agonist) decreased the amplitude of GABAA receptor‐mediated inhibitory postsynaptic currents (IPSCs) evoked by electric stimulation of afferent fibers (n=7; p<0.05). Prazosin (1uM, α1‐AR antagonist), blocked this effect. Paired‐pulse ratios were increased by phenylephrine application (n=13; p<0.05). Spontaneous IPSCs frequency but not amplitude, were decreased in presence of phenylephrine (n=7; p<0.05). However, frequency or amplitude of miniature IPSCs were not different (n=9; p>;0.05). Phenylephrine in low Ca2+ (1mM) concentration decreased IPSC amplitude (n=7; p<0.05). These results demonstrate that α1‐ARs at presynaptic terminals can modulate GABA release onto VTA‐DA cells. Drug‐induced changes in α1‐AR could contribute to the modifications occurring in the VTA during the addiction process. (Supported by GM‐08224 to CAJR; UIS to MCVM).