EVIDENCE THAT D-1 DOPAMINE-RECEPTORS CONTRIBUTE TO THE SUPERSENSITIVE BEHAVIORAL-RESPONSES INDUCED BY L-DIHYDROXYPHENYLALANINE IN RATS TREATED NEONATALLY WITH 6-HYDROXYDOPAMINE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 235  (2) , 287-295
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 the antagonism of this behavior by SCH-23390, a D-1 antagonist; induction of SMB in neonatal-6-OHDA-treated rats by the D-1 agonist, SKF-38393; the high correlation of the supersensitive locomotor responses to the D-1 agonist with the occurrence of L-dopa-induced SMB; and 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-17555 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. Such data suggest that differences in motor output observed between neonatally and adult 6-OHDA-treated rats are dependent upon adaptive mechanisms beyond these dopamine receptors. A facilitory interaction seems to occur between D1 and D-2 receptors because a dose of SKF-38393 that produced no SMB was found to do so when combined with the D-2 agonist, LY-17555. Comparison of the effects induced by L-dopa in neonatally 6-OHDA-treated rats with behavioral responses after specific D-1 and D-2 agonists indicate that neonatally 6-OHDA-treated rats have functionally supersensitive D-1 dopamine receptors which are critical for SMB and contribute to other behavioural responses induced by L-dopa. It appears that an increase in functional sensitivity of D-2 dopamine receptors also contributes to some of the behaviors in neonatally 6-LHDA-treated rats given L-dopa. A summary of behaviors associated with D-1 and D-2 dopamine receptors is provided and the significance of these results to symptoms of clinical syndromes with dopamine reduced are discussed.