Opioid drug discrimination: Characterization of the morphine stimulus

There have been few assessments of delta receptor activity in morphine drug discrimination learning (DDL) and these assessments have been limited to nonselective compounds or selective delta peptides administered i.c.v. Experiment 1 assessed the role of the delta receptor in the mediation of morphine drug discrimination by examining the ability of the systemically-administered, delta opioid agonist SNC80 to substitute for (and the delta opioid antagonist naltrindole to antagonize) morphine stimulus effects in rats trained to discriminate morphine from its vehicle in the conditioned taste aversion baseline of drug discrimination learning. Although morphine and methadone produced dose-related substitution for morphine (10 mg/kg), there was no evidence of substitution for morphine by SNC80 at any dose tested. Further, although naloxone (3.2 mg/kg) completely blocked the discriminative effects of morphine, naltrindole (3.2--10 mg/kg) did not significantly affect the morphine stimulus. These data suggest that the discriminative control established to morphine is mediated by its activity at the mu, but not the delta, receptor. The failure of SNC80 to substitute for morphine may be due to the general inability of activity at the delta receptor to support discrimination learning. To test this, Experiment 2 assessed the establishment of discriminative control by the selective delta agonist SNC80 in rats and its generalization to and antagonism by compounds relatively selective to the delta and mu receptor subtypes using the conditioned taste aversion baseline of DDL. Following acquisition, SNC80 and the delta agonist SNC162 produced SNC80-appropriate responding at a dose of 18 mg/kg. Conversely, the mu agonist morphine produced vehicle-appropriate responding at all doses tested. The discriminative effects of SNC80 were maximal at 20 min, partial at 120 min and lost at 240 min. These selective generalization patterns with SNC162 and morphine suggest that the discriminative effects of SNC80 were mediated at the delta, but not the mu, receptor, a conclusion supported by the fact that SNC80's discriminative control was completely blocked by the delta-selective antagonist naltrindole (NTI), but not by the mu-selective antagonist naltrexone. The present findings indicate that the discriminative effects of morphine are mediated at the mu, but not the delta, receptor.