Influence of previous exposure to levodopa on the interaction between dizocilpine and dopamine D1 and D2 agonists in rats with 6-hydroxydopamine-induced lesions.
The potential antiparkinson activity of N-methyl-D-aspartate antagonists was investigated by examining the effects of dizocilpine (MK-801) on rats with 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. MK-801, when administered alone to these animals, elicited ipsilateral rotation, which could be blocked by haloperidol. MK-801, at doses that did not produce rotation when given alone, inhibited the contralateral rotation produced by the D2 receptor agonist quinpirole but had no effect on the rotation induced by the D1 agonist SKF 38393 [(+-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8- diolhydrochloride]. However, exposure to levodopa 3 days previously resulted in a subsensitive rotational response to SKF 38393 and this subsensitivity to the D1 agonist was reversed by MK-801. The subsensitive rotational response to SKF 38393 was not evident 7 days after exposure to levodopa and MK-801 had no effect on the response to SKF 38393 at this time. These data suggest that N-methyl-D-aspartate receptor blockade can exert differential effects on dopamine agonist-induced rotational behavior that depend on which dopamine receptor subtype is activated and the previous exposure of the animal to dopamine agonists.
Boldry
R C
RC
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Chase
T N
TN
Engber
T M
TM
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*
D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007980:Levodopa; D016202:N-Methylaspartate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016291:Dizocilpine Maleate; D016627:Oxidopamine