Substance use disorder is associated with a high rate of relapse driven by the rewarding and motivational properties of drug-associated stimuli. We examined the extent to which the δ opioid receptor (DOR) mediated the conditioned reinforcing properties of drug-associated stimuli across 4 experiments and 2 operant procedures in Sprague-Dawley rats. In experiment 1, we assessed the extent to which SNC80 (DOR agonist) altered responding during extinction in a remifentanil self-administration procedure. In experiment 2, we assessed the extent to which SNC80 altered responding for a remifentanil-associated stimulus in the new response acquisition procedure. In experiment 3, we assessed the extent to which the effects of SNC80 were altered in standard versus enhanced stimulus control conditions in the new response acquisition procedure. In experiment 4, we assessed the extent to which naltrindole (DOR antagonist) was able to block SNC80-induced alterations in responding for a remifentanil-associated stimulus in the new response acquisition procedure. In experiment 5, we assessed the extent to which pretreatments of SNC80 altered Pavlovian conditioning in the new response acquisition procedure. These experiments support the role of the DOR system in mediating the rewarding properties of drug-associated stimuli, such that SNC80 dose-dependently enhanced responding for a remifentanil-associated stimulus across self-administration and new response acquisition procedures. These effects were blocked by naltrindole, demonstrating that these are DOR-mediated effects. DORs may represent a promising target to address relapse. SIGNIFICANCE STATEMENT: Conditioned reinforcing effects of an opioid-associated cue were enhanced following stimulation of δ opioid receptors (DORs), and this effect was blocked via DOR antagonism, which suggests the role of DORs in mediating drug-associated conditioned reinforcement.
原文链接
分享
引用
