DAMGO ([ d-ALA 2, nmephe 4, Gly-ol]enkephalin), but not DPLPE ([ d-pen 2, l-pen 5enkephalin), specifically inhibits methamphetamine-induced behavioral responses in the mouse

Abstract

The effects of intracerebroventricular (i.c.v.) injections of mu- and delta-selective opioid agonists on the methamphetamine-induced behavioral alterations in the mouse were determined by using multi-dimensional behavioral analyses. Methamphetamine (1.0 mg/kg) produced a marked increase in linear locomotion, circling, rearing and grooming behavior. Although the mu-selective opioid agonist [ d-Ala 2, NMePhe 4, Gly-ol]enkephalin (DAMGO) (0.003 and 0.01 μg) itself did not significantly affect different behavioral responses, DAMGO (0.003 and/or 0.01 μg) antagonized the methamphetamine (1.0 mg/kg)-induced increase in behavioral responses such as linear locomotion, circling, rearing and grooming. Additionally, the effects of DAMGO (0.01 μg) on the methamphetamine (1.0 mg/kg)-induced behavioral responses were fully reversed by pretreatment with the mu-selective alkylating agent β-funaltrexamine (β-FNA) (5.0 μg). In contrast, the delta-selective opioid agonist [ d-Pen 2, l-Pen 5]enkephalin (DPLPE) (0.3 or 1.0 μg) had no marked effects on the methamphetamine (1.0 mg/kg)-induced behavioral responses. These results suggest that the stimulation of mu but not delta opioid receptors plays an inhibitory role in the methamphetamine-induced behavioral responses.