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 i.p.) nor entacapone (30 mg/kg i.p.) 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.