Systemic and intra-accumbens administration of amphetamine differentially affects cortical acetylcholine release

The present experiments tested the hypothesis that the amphetamine-induced increase in dopamine release in the nucleus accumbens represents a necessar y and sufficient component of the ability of systemically administered amph etamine to stimulate cortical acetylcholine release. The effects of systemi c or intra-accumbens administration of amphetamine on accumbens dopamine re lease and cortical acetylcholine release were assessed simultaneously in aw ake animals equipped with dialysis probes inserted into the shell of the nu cleus accumbens and the medial prefrontal cortex. Additionally, the ability of intra-accumbens administration of dopamine D-1 and D-2 receptor antagon ists to attenuate the effects of systemic amphetamine on cortical acetylcho line was tested. The effects of all treatments were assessed in interaction with a stimulus-induced activation of cortical acetylcholine release to ac count for the possibility that the demonstration of the trans-synaptic effe cts of accumbens dopamine requires pre-activation of basal forebrain circui ts. Systemic amphetamine resulted in increases in basal cortical acetylchol ine and accumbens dopamine efflux. Intra-accumbens administration of amphet amine substantially increased accumbens dopamine efflux, but did not signif icantly affect cortical acetylcholine efflux. Furthermore, intra-accumbens administration of sulpiride or SCH 23390 did not attenuate the systemic amp hetamine-induced increase in cortical acetylcholine efflux. Collectively, the present data suggest that increases in accumbens dopamine release are neither sufficient nor necessary for the effects of systemical ly administered amphetamine on cortical acetylcholine release. The systemic amphetamine-induced increase in cortical acetylcholine may be mediated via multiple, parallel pathways and may not be attributable to a single affere nt pathway of the basal forebrain. (C) 2000 IBRO. Published by Elsevier Sci ence Ltd.