Evidence that D-1 dopamine receptors contribute to the supersensitive behavioral responses induced by L-dihydroxyphenylalanine in rats treated neonatally with 6-hydroxydopamine

Abstract

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)