Conditioned Place Preference Induced by a Combination of l-Dopa and a COMT Inhibitor, Entacapone, in Rats

KATAJAMÄKI, J., A. HONKANEN, T. P. PIEPPONEN, I.-B. LINDÉN, A. ZHARKOVSKY AND L. AHTEE. Conditioned place preference induced by a combination of l -dopa and a COMT inhibitor, entacapone, in rats. PHARMACOL BIOCHEM BEHAV 60(1) 23–26, 1998.—The interaction of dopamine (DA) precursor l-dopa and catechol-O-methyltransferase (COMT) inhibitor, entacapone, was examined in rats using conditioned place preference (CPP) paradigm to assess reinforcement, and by measuring DA metabolism in the striatum and the limbic forebrain. Neither l-dopa (100 mg/kg IP) nor entacapone (30 mg/kg IP) alone induced 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-MT), a metabolite reflecting DA release, and homovanillic acid (HVA) in both brain areas. l-dopa elevated limbic but not striatal 3-MT. l-dopa also slightly elevated limbic DA but had no effect on striatal DA concentration. l-Dopa–induced increase of 3-MT was attenuated by entacapone. Our results show for the first time that l-dopa is able to produce CPP in intact animals. This effect may be related to the findings that l-dopa increases synaptic DA concentrations in the limbic areas, and entacapone may enhance this elevation as it prevents the synaptic metabolism of DA.