3-O-methyl-DOPA is not involved in the development of behavioral supersensitivity after repeated L-dopa administration in 6-OHDA lesioned rats

• Published in: Behavioural brain research Vol. 63; no. 1; p. 41
• Main Authors: Bräutigam, K, Sohr, R, Morgenstern, R
• Format: Journal Article
• Language: English
• Published: Netherlands 29-07-1994
• Subjects: Animals; Apomorphine - pharmacology; Carbidopa - pharmacology; Catechol O-Methyltransferase Inhibitors; Corpus Striatum - drug effects; Levodopa - pharmacology; Male; Methyldopa - pharmacology; Motor Activity - drug effects; Oxidopamine - pharmacology; Rats; Rats, Wistar; Receptors, Dopamine - drug effects; Stereotyped Behavior - drug effects; Substantia Nigra - drug effects
• ISSN: 0166-4328
• DOI: 10.1016/0166-4328(94)90049-3

The underlying cause of long-term complications of L-DOPA therapy in Parkinson's disease is largely unknown. Recently, centrally and peripherally acting catechol-O-methyltransferase (COMT) inhibitors became available. These drugs are capable of inhibiting the generation of 3-O-methyl-DOPA (3-OMD), a major metabolite of L-dopa developing considerable plasma levels during L-dopa therapy. The use of these drugs offers the opportunity to study the involvement of 3-OMD in the development of behavioral supersensitivity following repeated doses of L-dopa over 11 days in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic system. Repeated daily administration of L-dopa/Carbidopa produced continuous increase of contralateral rotations to both L-dopa/Carbidopa and to challenge doses of apomorphine. This increase was not influenced by peripherally and peripherally plus centrally acting COMT inhibitors, OR-462 and OR-486, respectively, administered simultaneously with L-dopa/Carbidopa. Both COMT inhibitors suppressed the L-dopa induced increase of 3-OMD plasma levels, OR-486 being more effective than OR-462. This indicates that 3-OMD is not involved in the development of behavioral supersensitivity following repeated L-dopa treatment in rats with unilateral 6-OHDA lesion of the nigrostriatal system.