Combination of a delta opioid receptor agonist but not a mu opioid receptor agonist with the D1-selective dopamine receptor agonist SKF 38393 markedly potentiates different behaviors in mice.

The effects of intracerebroventricular injections of opioid peptides selective for mu or delta opioid receptors on behaviors induced by the D1 dopamine agonist SKF 38393 were investigated by using multi-dimensional behavioral analyses. A 10.0 mg/kg dose of SKF 38393 produced a marked increase in grooming behavior. The SKF 38393 (10.0 mg/kg)-induced increase in grooming behavior was clearly antagonized by SCH 23390 (0.03 mg/kg), a D1 dopamine antagonist, but not by S(-)-sulpiride (10.0 mg/kg), a D2 dopamine antagonist. [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO) (0.003 and 0.01 microgram), a mu-selective agonist, or [D-Pen2,L-Pen5]enkephalin (DPLPE) (0.3 or 1.0 microgram), a delta-selective agonist, failed to affect spontaneous behaviors. The combination of DPLPE (0.3 and 1.0 microgram) but not of DAMGO (0.003 and 0.01 microgram) with SKF 38393 (10.0 mg/kg) produced a marked increase in linear locomotion and circuling away from the side receiving the peptide, whereas grooming behavior was not affected. The effects induced by DPLPE (1.0 microgram) plus SKF 38393 (10.0 mg/kg) were fully reversed by the delta-selective opioid antagonist naltrindole (10.0 mg/kg), SCH 23390 (0.03 mg/kg) and S(-)-sulpiride (10.0 mg/kg). These findings suggest that delta but not mu opioid systems interact with D1 dopamine receptors, resulting in a marked increase in linear locomotion and contralateral circuling without causing marked changes in grooming behavior.