Delta opioid discrimination learning in the rat: Assessment with the selective delta agonist SNC80

Abstract The majority of reports assessing opioid drug discrimination learning (DDL) have concentrated on characterizing the stimulus properties of compounds selective for mu and kappa opioid receptors. Assessments of delta opioid DDL have been limited and, to date, these assessments have been restricted to the monkey and pigeon. No assessment of delta stimulus control has been examined in rodents. To that end, the present experiment examined 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. Animals injected with 5.6 mg/kg of SNC80 prior to a saccharin–LiCl pairing and with the SNC80 vehicle prior to saccharin alone acquired the discrimination within seven conditioning cycles. The discriminative effects of SNC80 were maximal at 20 min, partial at 120 min, and lost at 240 min. The discrimination was dose dependent in that as the dose of SNC80 increased, the amount of saccharin consumed decreased. In subsequent generalization tests, 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. These selective generalization patterns with SNC162 and morphine suggest that the discriminative effects of SNC80 are 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 NTI, but not by the mu-selective antagonist naltrexone. The present findings indicate that not only do rats readily discriminate both mu- and kappa-selective agonists from their respective vehicles, but they also discriminate compounds that are selective for the delta receptor subtype, thus extending the class of compounds that can serve such discriminative functions for the rat.