Elsevier

Brain Research

Volume 605, Issue 2, 12 March 1993, Pages 332-337
Brain Research

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

https://doi.org/10.1016/0006-8993(93)91761-GGet rights and content

Abstract

Different groups of rats received three injections of eitherd-amphetamine (2.5 μg/0.5 μl/ 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 systemicd-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.

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    This research was supported by a gran from the Ontario Mental Health Foundation. Thed-amphetamine was supplied by SmithKline Beecham Pharma Inc. Technical assistance was provided by Bogdan Zurakowski.

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