USE OF ANTISENSE OLIGODEOXYNUCLEOTIDE TO DETERMINE DELTA-OPIOID RECEPTOR INVOLVEMENT IN [D-ALA(2)]DELTORPHIN II-INDUCED LOCOMOTOR HYPERACTIVITY

Intracerebroventricularly (i.c.v.) administered [D-Ala(2)]deltorphin I I (20 mu g) produced a marked locomotor hyperactivity in male ICR mice . The locomotor hyperactivity induced in response to i.c.v. [D-Ala(2)] deltorphin II (20 mu g) was suppressed by pretreatment with naltriben (NTB, 10 mu g) but not 7-benzylidene naltrexone (BNTX, 1 mu g) and D-P he-Cys-Tyr-D-Try-Orn-Thr-Phe-Thr-NH2 (CTOP, 100 ng). The influence of antisense oligodeoxynucleotide to delta-opioid receptor mRNA (delta-AS oligo) or a mismatch oligodeoxynucleotide (MM oligo) on the locomotor hyperactivity induced by [D-Ala(2)]deltorphin II was determined. Grou ps of mice pretreated i.c.v. with delta-AS oligo (1 mu g), MM oligo (1 mu g) or saline (4 mu l) once a day for 3 days, were injected i.c.v. [D-Ala(2)]deltorphin II (10 or 20 mu g) and the locomotor response to [D-Ala(2)]deltorphin II was measured. The locomotor hyperactivity of i .c.v. [D-Ala(2)]deltorphin II (10 or 20 mu g) were significantly suppr essed by i.c.v. pretreatment with delta-AS oligo but not MM oligo. The present results indicate that pretreatment with delta-AS oligo suppre sses mouse locomotor hyperactivity produced by stimulation of delta(2) -opioid receptors in the brain.