Effects of [D-Ala 2, D-Leu 5]enkephalin and [D-Pen 2, L-Pen 5]enkephalin on apomorphine-induced motor activity in the mouse

Abstract

The effects of intracerebroventricular injections of opioid peptides such as DADL ([D-Ala 2, D-Leu 5]enkephalin) and DPLPE ([D-Pen 2, L-Pen 5]enkephalin) with different degrees of selectivity for delta- over mu-receptor on apomorphine (0.1, 0.3, 1.0 and/or 3.0 mg/kg)-induced motor activity were investigated in the mouse using multi-dimensional behavioral analyses. Lower doses (0.1 and 0.3 mg/kg) of apomorphine failed to affect significantly motor activity, whilst higher doses (1.0 and 3.0 mg/kg) of the drug produced a marked increase in linear locomotion, circling, rearing, and/or grooming behaviors. DADL (0.03, 0.1 or 0.3 μg) by itself did not influence behaviors, while the peptide (0.1 and 0.3 μg) produced a marked inhibition on apomorphine (1.0 but not 3.0 mg/kg)-induced increase in rearing behaviors. Furthermore, the inhibitory effect of DADL (0.3 μg) on the apomorphine (1.0 mg/kg)-induced increase in rearing was reversed by treatment with the alkylating agent β-FNA (β-funaltrexamine) (5.0 μg). In contrast to the effects of DADL, the much more delta-selective opioid agonist DPLPE (0.3, 1.0 or 1.75 μg) had no marked effects on apomorphine (1.0 mg/kg)-induced behaviors. These results suggest that delta opioid receptors do not play a principal role in the apomorphine-induced increase in circling, rearing or grooming behaviors.