Opioid peptides selective for receptor types modulate cocaine-induced behavioral responses in mice

The effects of intracerebroventricular injection of mu-, kappa- and delta-selective opioid agonists on cocaine-induced behavior were investigated in mice using multidimensional behavioral analysis. Cocaine (3.0 mg/kg) produced a marked increase in linear locomotion, circling, rearing and/or grooming, although the mu-opioid agonist [D-Ala2, NMePhe4, Gly-ol] enkephalin (DAMGO) (0.003 and 0.01 microgram), the kappa-opioid agonist dynorphin A- (1-13) (3.0 and 12.5 micrograms) or the delta-opioid agonist [D-Pen2, L-Pen5]enkephalin (DPLPE) (0.3 and 1.0 micrograms) did not significantly affect behavioral responses. DAMGO (0.003 and 0.01 microgram) and dynorphin A- (1-13) (12.5 micrograms) inhibited the cocaine (3.0 mg/kg)-induced increase in linear locomotion, circling and/or rearing. In contrast, DPLPE (1.0 micrograms) enhanced the cocaine (3.0 mg/kg)-induced increase in circling. The effects of DAMGO (0.003 microgram), dynorphin A- (1-13) (12.5 micrograms) and DPLPE (1.0 micrograms) were fully reversed by receptor-selective opioid antagonists, such as beta-funaltrexamine (5.0 micrograms), Mr2266 (5.6 mg/kg) and naltrindole (10.0 mg/kg), respectively. These results suggest that the activation of mu- and kappa-opioid receptors inhibits cocaine-induced behavior, while that of delta-opioid receptors enhances the behavior.