Discriminative stimulus effects of a centrally administered, delta-opioid peptide (D-Pen2-D-Pen5-enkephalin) in pigeons

The present study assessed the discriminative stimulus effects of the delta-opioid agonist [D-Pen2-D-Pen5]enkephalin (DPDPE) in pigeons. Food-restricted pigeons were trained to discriminate between i.c.v injections of 100 micrograms [D-Pen2-D-Pen5]enkephalin (DPDPE) and saline in a two-key operant procedure; acquisition of discriminative control was rapid (14-28 daily sessions). [D-Ser2, Leu5, Thr6]enkephalin (DSLET) and [D-Ala2]deltorphin II, peptides selective for delta-opioid receptors, produced discriminative stimulus effects similar to DPDPE, and were approximately equipotent to DPDPE. The non-peptidic, delta-opioid agonist BW373U86 (0.032-100 mg/kg, i.m.) partially generalized to DPDPE. The kappa-opioid agonist U69,593 (0.01-1 mg/kg, i.m.), and the mu-opioid agonists, DAMGO (0.1-3.2 micrograms, i.c.v) and morphine (1-10 mg/kg, i.m.), did not produce discriminative stimulus effects similar to DPDPE, up to doses that markedly decreased response rates. Naltrindole (0.1 mg/kg. i.m.), an antagonist selective for delta-opioid receptors, produced approximately a 30-fold reduction in the potency of DPDPE. DPDPE's discriminative stimulus effect in pigeons appears to be mediated through a delta-opioid receptor; this effect may provide a procedure for assessing delta-opioid receptor function in vivo.