Amphetamine injected into the ventral tegmental area sensitizes the nucleus accumbens dopaminergic response to systemic amphetamine: an in vivo microdialysis study in the rat.

Different groups of rats received three injections of either D-amphetamine (2.5 micrograms/0.5 microliters/side) or saline into the ventral tegmental area (VTA), one injection every third day. Two weeks following the last injection, dopamine (DA) neurotransmission in the nucleus accumbens (N. Acc.) was assessed with in vivo microdialysis before and after a challenge with systemic D-amphetamine (1.0 mg/kg, i.p.). Prior to challenge, basal extracellular concentrations of DA in the N.Acc. did not differ in VTA amphetamine- and saline-preexposed animals. Following challenge, however, both groups showed an increase in N.Acc. DA but this was significantly greater (2-fold) in VTA amphetamine-preexposed animals. These latter animals also showed significantly higher DA metabolite levels in comparison to saline-preexposed animals prior to (DOPAC) as well as after challenge (HVA). These findings extend those of behavioral experiments showing that intra-VTA amphetamine produces sensitized locomotor responding to drug challenge (J. Pharmacol. Exp. Ther., 245 (1988) 1095-1102; Brain Res., 516 (1990) 99-106; Ann. NY Acad. Sci., 654 (1992) 444-447) and demonstrate that amphetamine applied to the somatodendritic region of mesolimbic DA neurons sensitizes these neurons as evidenced by their enhanced N.Acc. DA response to a systemic amphetamine challenge.