Suppression of cocaine- and food-maintained behavior by the D2-like receptor partial agonist terguride in squirrel monkeys

Abstract

Rationale: The D2-like receptor partial agonist terguride has a profile of behavioral effects in rats that suggests potential benefit as a pharmacotherapy for cocaine addiction.

Objectives: The present study investigated the effects of terguride on cocaine- and food-maintained behavior in squirrel monkeys.

Methods: Squirrel monkeys were trained to respond on a second-order schedule (FI 10 min, FR 10 or 30:S) of either i.v. cocaine injection or food pellet delivery. Additional monkeys were studied using quantitative observational techniques to construct side effect profiles. Under each procedure, the effects of terguride were compared with those of the reference D2-like receptor antagonist nemonapride and the D2-like receptor full agonist quinpirole.

Results: Terguride and nemonapride, but not quinpirole, dose-dependently reduced cocaine-maintained behavior. In animals self-administering food, terguride decreased response rates at doses lower than those required to suppress cocaine-maintained behavior. Effective doses of terguride had no systematic effect on motor activity or muscle rigidity, whereas effective doses of nemonapride virtually eliminated motor activity and induced severe catalepsy. The primary observable effects of terguride were a modest increase in self-directed behavior (a D2-receptor agonist-like effect) at intermediate doses and a small increase in static posture (a D2-receptor antagonist-like effect) at the highest dose tested.

Conclusions: The results suggest that terguride has advantages over conventional D2-like receptor antagonists and agonists as a candidate pharmacotherapy for cocaine abuse; however, terguride significantly reduces food-maintained behavior at lower doses than those needed to decrease cocaine-maintained behavior suggesting limitations on the utility of terguride as a medication for cocaine addiction.