Conditioned place preference induced by a combination of L-dopa and a COMT inhibitor, entacapone, in rats.
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.
Katajamäki
J
J
Department of Pharmacy, University of Helsinki, Finland.
Honkanen
A
A
Piepponen
T P
TP
Lindén
I B
IB
Zharkovsky
A
A
Ahtee
L
L
D000818:Animals; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007980:Levodopa / Q000008:administration & dosage*; D008032:Limbic System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009570:Nitriles; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; C001746:3-methoxytyramine; D004298:Dopamine