Modulation of cocaine-induced motor activity in the rat by opioid receptor agonists.

Selective opioid-receptor agonists were tested in combination with cocaine to determine the effect on the motor activity of rats. Cocaine produced dose-dependent increases in locomotor activity (distance traveled). The cocaine-induced increase in locomotor activity was potentiated by the selective delta-opioid receptor agonist [D-Pen2-D-Pen5]enkephalin (DPDPE). This potentiation was blocked by the general opioid receptor antagonist naltrexone, as well as by the selective opioid receptor antagonists beta-FNA (mu-opioid receptor) and naltrindole (delta-opioid receptor). DPDPE also potentiated the increase in locomotor activity produced by the selective dopamine reuptake inhibitor GBR12909, but not that produced by the direct dopamine receptor agonist apomorphine. Cocaine-induced motor activity was potentiated by the activation of central delta-opioid receptors. The synergistic effect seen with delta-opioid receptor activation may involve a mu-opioid receptor component, and is probably mediated via a dopaminergic pathway.