The Effects of Delta Opioid Receptors Activation on the Acquisition of Responding for an Opioid‐associated Stimulus

Abstract

Drug-associated stimuli take on conditioned reinforcing properties that promote drug-seeking and relapse. Previous research has shown that, following response-independent infusions of remifentanil (mu opioid receptor agonist) paired with a stimulus, rats learned to make a novel response for presentations of an opioid-associated stimulus to a greater extent than control rats. Further, research has demonstrated that stimulating delta opioid receptors in the nucleus accumbens results in dose-dependent increases in drug-seeking. In the current experiment, we assessed the extent to which activating delta opioid receptors via a systemic injection of SNC80 modified the conditioned reinforcing properties of an opioid-associated stimulus. We hypothesized that pre-session injections of SNC80 would increase the conditioned reinforcing properties of the remifentanil-associated stimulus. First, we exposed rats to 20 i.v. infusions of remifentanil (0, 1.0, or 3.2 mcg/kg/infusion) and 20 stimulus presentations that were delivered response-independently each day for 5 days. For the experimental group (Paired Conditioning), the remifentanil infusions and stimulus presentations were delivered concurrently. The control group (Random control) received the same number of infusions and stimulus presentations, but they were not explicitly paired. For the next 7 sessions (acquisition), we tested the extent to which the stimulus functioned as a conditioned reinforcer by allowing rats to freely respond via a nosepoke for presentations of the remifentanil-associated stimulus only. Prior to each acquisition session, rats received an injection of SNC80 (0, 1.0, or 3.2 mg/kg). We found that rats in the Paired Pavlovian Conditioning group responded for the remifentanil-associated stimulus significantly more than controls (p = 0.005, hp2 = 0.09). In addition, SNC80 increased responding for remifentanil-associated stimuli relative to vehicle treatment (p < 0.001, hp2 = 0.35). These findings demonstrated that a remifentanil-associated stimulus takes on conditioned reinforcing properties and that the conditioned reinforcing properties of the stimulus was augmented by delta opioid receptor activation. This may suggest that delta opioid receptors may play a role in mediating conditioned reinforcing properties.