Conditioned place preference induced by a combination of L-dopa and a COMT inhibitor, entacapone, in rats

Pharmacol Biochem Behav. 1998 May;60(1):23-6. doi: 10.1016/s0091-3057(97)00394-8.


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.

MeSH terms

  • Animals
  • Catechol O-Methyltransferase Inhibitors*
  • Catechols / administration & dosage*
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology
  • Dopamine / analogs & derivatives
  • Dopamine / metabolism
  • Drug Synergism
  • Enzyme Inhibitors / administration & dosage*
  • Levodopa / administration & dosage*
  • Limbic System / drug effects
  • Limbic System / physiology
  • Male
  • Nitriles
  • Rats
  • Rats, Wistar
  • Reinforcement, Psychology
  • Synapses / drug effects
  • Synapses / metabolism


  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Enzyme Inhibitors
  • Nitriles
  • Levodopa
  • entacapone
  • 3-methoxytyramine
  • Dopamine