Evidence that D-1 dopamine receptors contribute to the supersensitive behavioral responses induced by L-dihydroxyphenylalanine in rats treated neonatally with 6-hydroxydopamine.
The present investigation supports the hypothesis that functionally supersensitive D-1 dopamine receptors are involved in the self-mutilation behavior (SMB) induced by L-dihydroxyphenylalanine (L-dopa) in rats treated neonatally with 6-hydroxydopamine (6-OHDA). This conclusion is based upon 1) the antagonism of this behavior by SCH-23390, a D-1 antagonist; 2) induction of SMB in neonatal-6-OHDA-treated rats by the D-1 agonist, SKF-38393; 3) the high correlation of the supersensitive locomotor responses to the D-1 agonist with the occurrence of L-dopa-induced SMB; and 4) the inability of the D-2 agonist, LY-171555, to induce SMB in rats treated neonatally with 6-OHDA. The specificity of SCH-23390 and SKF-38393 for the D-1 dopamine receptor was supported by the absence of action of SCH-23390 against locomotor activities induced by LY-171555 and its blockade of SKF-38393-induced locomotion in 6-OHDA-treated rats. Behavioral responses to D-1 and D-2 agonists did not show the same profile in adult and neonatally 6-OHDA-treated rats, providing further support for the view that the age at which dopaminergic neurons are destroyed has differing effects on motor output. Many of the behaviors observed when the D-2 dopamine receptor was activated by LY-171555 were apparent after SKF-38393 in neonatally 6-OHDA-treated rats. Similar behavioral responses to the D-1 and D-2 agonists were also observed in adult 6-OHDA-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000494:pharmacology*; D004347:Drug Interactions; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D005475:Flupenthixol / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D011247:Pregnancy; D019257:Quinpirole; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D012652:Self Mutilation / Q000139:chemically induced; D013239:Stereotyped Behavior / Q000187:drug effects
D001552:Benzazepines; D004873:Ergolines; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D019257:Quinpirole; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D005475:Flupenthixol; D006220:Haloperidol