Rats choose cocaine over dopamine agonists in a two-lever self-administration preference test

Abstract

Rats will self-administer dopamine D 1 and D 2 agonists, alone or in combination. Response rates and patterns for the D 1:D 2 combinations are nearly identical to those induced by cocaine. Here we examine whether rats prefer cocaine over D 1 or D 2 agonists presented alone or in D 1:D 2 combinations. During daily 3-h tests in a two-lever box, cocaine was available at either the right or left lever and the active side was alternated daily. After response rates had stabilized (±10% for 2 days), different groups were offered cocaine (800 μg/kg/injection) at one lever and either another dose (267, 1600, or 2400 μg/kg/injection) of cocaine or a dopamine agonist at the other lever. Animals consistently chose the higher of the presented cocaine doses over the low cocaine dose (267 μg). In choices between cocaine and dopamine agonists, the preferred cocaine dose (800 μg) was chosen over doses of the D 1 (SKF 82958) or D 2 ((+)-PHNO) agonist. However, no preference was shown between 800 μg cocaine and D 1:D 2 agonist mixtures, and the high-dose agonist mixture was preferred to the low cocaine dose. These results suggest that neither D 1 nor D 2 agonists alone fully duplicate the reinforcing actions of cocaine, but agonist combinations may approximate cocaine's reinforcement strength.