Pain‐Related Depression of Operant Responding Maintained by Social Access or Food in Male and Female Rats

Abstract

Background Clinically relevant pain is often associated with functional impairment and behavioral depression, and restoration of function is a major goal of treatment. Social interaction is one class of behavior that can be depressed by pain states, and candidate analgesics would ideally restore pain-depressed social behavior. To develop an assay of pain-related social impairment, this study compared the impact of pain ± analgesic treatment on operant responding maintained either by social access to a familiar conspecific or by food in male and female rats. We hypothesized that a pain manipulation would produce an analgesic-reversible decrease in operant responding maintained by either reinforcer. Methods For social reinforcement, adult male and female Sprague-Dawley rats were initially housed in same-sex pairs before separation into individual housing prior to training. One rat in each pair was designated as the “responder” rat, the other was designated as the “reinforcer” rat, and 30-min behavioral sessions were conducted each weekday in operant social-choice self-administration chambers with two adjacent compartments separated by a guillotine door. The responder-rat compartment contained a response lever, stimulus light over the lever, and house light, and responding under a fixed-ratio 1 (FR 1) schedule opened the door to allow 30-sec access through a grate to the reinforcer rat in the other compartment. After responding stabilized, responder rats were tested with four manipulations: (1) increased FR requirements (FR1-FR16), (2) an acute visceral noxious stimulus alone (intraperitoneal injection of dilute lactic acid at concentrations of 0-1.8%; IP acid), (3) an analgesic alone [subcutaneous injection of the mu opioid receptor agonist morphine (0.32-10 mg/kg) or the cyclooxygenase1/2inhibitor ketoprofen (10 mg/kg)], and (4) morphine or ketoprofen as a pretreatment to IP acid. Parallel studies were conducted in a separate group of rats responding under an FR 1:Timeout 30-s schedule for delivery of 45 mg grain pellets. Results Baseline responding was lower for social access than for food. Increased FR values, IP acid alone, and morphine alone all decreased responding for both social access and food, but responding for social access was more sensitive to all these manipulations. Morphine failed to alleviate 1.0% IP acid-induced depression of social reinforcement, and ketoprofen produced a significant but only partial effect. Both morphine and ketoprofen alleviated 1.8% IP acid-induced depression of food-maintained responding, but only morphine was effective against 3.2% acid, and neither morphine nor ketoprofen was effective against 5.6% acid. Conclusions Taken together, these results suggest that the social stimulus used here was a weaker reinforcer than the food stimulus, and pain-related depression of operant responding maintained by this social stimulus may be more difficult to restore with analgesics than pain-related depression of responding maintained by the stronger food reinforcer.