CONDITIONED PLACE PREFERENCE INDUCED BY A COMBINATION OF L-DOPA AND ACOMT INHIBITOR, ENTACAPONE, IN RATS

The interaction of dopamine (DA) precursor L-dopa and catechol-O-methy ltransferase (COMT) inhibitor, entacapone, was examined in rats using conditioned place preference (CPP) paradigm to assess reinforcement, a nd by measuring DA metabolism in the striatum and the limbic forebrain . Neither L-dopa (100 mg/kg IF) nor entacapone (30 mg/kg IF) alone ind uced CPP, but in combination they induced significant CPP. Entacapone alone had no effect on limbic or striatal DA concentrations, while it reduced the concentrations of the COMT products 3-methoxytyramine (3-M T), a metabolite reflecting DA release, and homovanillic acid (HVA) in both brain areas. L-dopa elevated limbic but not striatal 3-MT. L-dop a also slightly elevated limbic DA but had no effect on striatal DA co ncentration. L-Dopa-induced increase of 3-MT was attenuated by entacap one. Our results show for the first time that L-dopa is able to produc e CPP in intact animals. This effect may be related to the findings th at L-dopa increases synaptic DA concentrations in the limbic areas, an d entacapone may enhance this elevation as it prevents the synaptic me tabolism of DA. (C) 1998 Elsevier Science Inc.