Continuous and intermittent levodopa differentially affect rotation induced by D-1 and D-2 dopamine agonists.
The effects of continuous and intermittent levodopa treatment on rotational behavior induced by dopamine agonists were examined in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway. Chronic administration of levodopa by continuous infusion (90-100 mg/kg per day i.p. by osmotic pump for 19 days with a 3 day washout) enhanced the rotational response to the D-2 dopamine receptor agonist quinpirole, but had no effect on rotation induced by the D-1 agonist SKF 38393 or that due to the non-selective dopamine agonist apomorphine. The rotational responses to the selective dopamine agonists differed dramatically in rats treated with levodopa by intermittent injection (45-50 mg/kg i.p., b.i.d. for 19 days with a 3 day washout): they showed a markedly increased response to quinpirole, a greatly diminished response to SKF 38393, and a modestly enhanced response to apomorphine. Continuous and intermittent treatment resulted in equivalent daily plasma levodopa levels. These findings suggest that the intermittence of central dopamine receptor stimulation may be an important factor in determining the subsequent responses of the dopamine system. The dissociation between the effects of both continuous and intermittent levodopa on D-1 and D-2 agonist-induced rotation indicates that D-1 and D-2 dopamine receptor-mediated mechanisms respond differently to chronic levodopa treatment.
Engber
T M
TM
Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Susel
Z
Z
Juncos
J L
JL
Chase
T N
TN
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects
D015259:Dopamine Agents; D006892:Hydroxydopamines; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine