Behavioural and biochemical changes following chronic administration of L-dopa to rats.
Rats were given powdered diet containing L-DOPA (together with the peripheral decarboxylase inhibitor carbidopa) for a period of 6 months. The estimated daily intake was in the range 20-30 mg/kg. Initially, at 1 week and 1 month, L-DOPA-fed rats exhibited enhanced spontaneous locomotor activity, but this fell to within the control range by 3 and 6 months, although (+)-amphetamine-induced hyperactivity was greater at 6 months in L-DOPA-treated animals than in control rats. Six months after receiving L-DOPA in their diet rats showed enhanced stereotypy scores to a series of dopamine agonists administered acutely including (+)-amphetamine, nomifensine, L-DOPA, apomorphine and piribedil compared with the control animals. In another behaviour test L-DOPA administration reduced the cataleptic potency of both fluphenazine and haloperidol was increased. Biochemically 6 months treatment of rats with L-DOPA was associated with significantly increased plasma concentrations of L-DOPA, enhanced striatal levels of L-DOPA, dopamine and dopamine metabolites, enhanced specific binding (as indicated by increased Bmax values) of [3H] spiroperidol, [3H] ADTN and [3H] 5-HT to striatal membranes, and increased basal and dopamine-stimulated striatal adenylate cyclase activity. The results are discussed in the light of changes of sensitivity of cerebral dopamine receptors, an increase in receptor numbers, and the tolerance to L-DOPA which often develop in the treatment of Parkinson's disease.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D004032:Diet; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D011954:Receptors, Dopamine; D007980:Levodopa; D000661:Amphetamine; D000262:Adenylyl Cyclases