PARAMETRIC AND PHARMACOLOGICAL ANALYSES OF THE ENHANCED GROOMING RESPONSE ELICITED BY THE D1 DOPAMINE RECEPTOR AGONIST SKF-38393 IN THE RAT

The present report investigated several parametric and pharmacological aspects of the enhanced self-grooming behavior of rats following systemic administration of the selective D1 dopamine (DA) receptor agonist SKF 38393. The amount of time that rats spent grooming themselves was measured continuously for 30 min following drug administration to provide a quantitative measure of the drug-induced behavior. SKF 38393 increased the amount of grooming in a dose-dependent manner (0.5-16 mg/kg, SC). The onset of this effect required at least 5 min and it persisted for at least 60 min. The ability of SKF 38393 to enhance grooming was shared by R-SKF 38393, but not S-SKF 38393, consistent with the affinities of these enantiomers for the D1 DA receptor. Unlike SKF 38393, the peripheral D1 agonist fenoldopam (SKF 82526) failed to cause an increased grooming response, suggesting a central site of action for elicitation of this behavior. The SKF 38393-induced increase in grooming was competitively antagonized by the D1 selective antagonist SCH 23390 (0.5 mg/kg, SC). Although the D2 DA receptor-selective antagonist eticlopride reduced SKF 38393-elicited grooming, this antagonism appeared to be of a physiological rather than pharmacological nature. When eticlopride was coadministered with the non-selective (mixed) D1/D2 agonist apomorphine, an increase in grooming behavior similar to that produced by SKF 38393 was observed. Inactivation of D1 and D2 DA receptors produced by pretreatment with the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ), at a dose which reduces D1 and D2 receptor density by greater-than-or-equal-to 50% (8.0 mg/kg, IP), reduced SKF 38393-induced grooming by approximately 50%. Prior protection of D1 receptors by SCH 23390 completely prevented the effect of EEDQ whereas prior protection of D2 receptors by eticlopride did not. These results demonstrate that enhanced grooming behavior elicited by dopamine agonists in rats, when measured as the amount of time spent grooming, provides a reliable, quantifiable index of selective D1 DA receptor activation in the CNS. In addition, this behavior does not appear to require concurrent stimulation of D2 DA receptors by endogenous DA.