The present study was designed to investigate the effects of centrally administered neuropeptides on the discriminative stimulus properties of cocaine in the rat. Rats were trained to discriminate 10.0 mg/kg of cocaine from vehicle in a shock avoidance paradigm. The mu-selective opioid agonist [D-Ala(2),NMePhe(4), Gly-ol]enkephalin (DAMGO) (0.03-0.3 mu g, ICV) or the kappa-selective opioid agonist dynorphin A-(1-13) (1.0-10.0 mu g, ICV) did not generalize to cocaine cue, although the delta-selective opioid agonist [D-Pen(2),L-Pen(5)]enkephalin (DPLPE) (10.0 mu g, ICV) reportedly generalizes to it through the mediation of delta-opioid receptors. Thyrotropin-releasing hormone (10.0-56.0 mu g, ICV), somatostatin (0.3-3.0 mu g, ICV), substance P (3.0-17.5 mu g, ICV), or neurotensin (3.0-17.5 pg, ICV) did not produce any stimulus effects in common with cocaine. It appears that neuropeptides other than the delta-selective opioid do not play a major role in the discriminative stimulus properties of cocaine.