Behavioral Effects of Cocaine in the Presence or Absence of Chronic Neuropathic Pain

Abstract ID 96428 Poster Board 299 Chronic pain affects approximately 1 in 5 Americans. It has been suggested that chronic pain alters the reward pathway; for example, that pain prevents the development of cocaine-induced conditioned place preference. However, no studies have directly evaluated the reinforcing effects of cocaine in the presence of chronic neuropathic pain. Therefore, the goal of this project was to examine if chronic neuropathic pain would alter reinforcing effects and discriminative stimulus effects of cocaine in Sprague Dawley rats. To induce chronic pain, we used a preclinical model of chronic neuropathic pain called the Spared Nerve Injury (SNI) in which hypersensitivity to noxious stimuli persists for >8 mo. Operant behaviors were established prior to the induction of chronic pain or sham states. In self-administration studies, daily, within-subject dose effect curves were evaluated in multi-component session comprised of five 25-min components, in which one dose (0, 0.032, 0.1, 0.32,or 0.56 mg/kg/inf cocaine) was available per component under a fixed ratio (FR) 5 schedule of reinforcement. To evaluate the discriminative stimulus of cocaine, rats were trained to discriminate 5.6 mg/kg cocaine (i.p.) from saline under a FR10 schedule of reinforcement, such that responding in the injection-appropriate aperture resulted in delivery of 45 mg sucrose pellets. Prior to either SNI or sham surgery, cocaine maintained responding in a dose-dependent manner in all rats. After induction of sham or SNI states, there was no change in the self-administration of cocaine in either sham or SNI groups over the course of 4 weeks. In drug discrimination experiments, cocaine and amphetamine produced dose-dependent increases in cocaine-appropriate responding that did not significantly change over the course of 4 months of sham or SNI states. Prior to surgery, the dopamine D2/3 receptor agonist quinpirole (doses tested) produced on average <30% cocaine-appropriate responding; however, after SNI surgery, quinpirole produced significantly more cocaine- appropriate responding than pre-surgery and than that observed in sham rats. Collectively, SNI induced chronic neuropathic pain failed to alter the reinforcing effects of cocaine or the discriminative stimulus effects of cocaine but enhanced quinpirole generalization to the cocaine discriminative stimulus, suggesting that SNI may increase the expression or activity of dopamine D2-like receptors. Future studies should further evaluate changes in the behavioral effects of direct dopamine D1- and D2-like receptor agonists in a chronic neuropathic pain state.