Left and right 6-hydroxydopamine lesions of the medial prefrontal cortex differentially affect voluntary ethanol consumption

Dopaminergic projections to the medial prefrontal cortex (mPFC) were unilat erally lesioned with 6-hydroxydopamine (6-OHDA) to examine how dopamine (DA ) asymmetry in the mPFC influences voluntary ethanol consumption. Differenc es in nucleus accumbens (NAS) DA neurotransmission have been related to ind ividual differences in locomotor activity and in the rewarding efficacy of ethanol. Therefore, differences in locomotor activity were used to further characterize the effects of unilateral mPFC 6-OHDA lesions on ethanol consu mption. Male Long Evans rats were assessed for high versus low levels of sp ontaneous locomotor activity. DA terminals in the left or right mPFC were u nilaterally lesioned with 6-OHDA, resulting in an average DA depletion of 5 4% and 50%, respectively. After a minimum seven-day recovery period, prefer ence for a 10% ethanol solution vs. water was determined in a 24-h 2-bottle home-cage free-choice paradigm. Left mPFC 6-OHDA lesions increased and rig ht lesions decreased ethanol consumption. These differential effects of lef t and right lesions were primarily attributable to rats exhibiting low loco motor activity prior to surgery. The present data suggest that right greate r than left cortical DA asymmetry in combination with low endogenous NAS DA (predicted by low locomotor activity levels) may increase the vulnerabilit y to abuse ethanol. (C) 1999 Elsevier Science B.V. All rights reserved.