Acute pain-related depression of operant responding maintained by social interaction or food in male and female rats.

RATIONALE: Clinically relevant pain is often associated with functional impairment and behavioral depression, including depression of social behavior. Moreover, recovery of function is a major goal in pain treatment. We used a recently developed model of operant responding for social interaction in rats to evaluate the vulnerability of social behavior to an experimental pain manipulation and the sensitivity of pain-depressed social behavior to treatment with clinically effective analgesics. METHODS: Sprague-Dawley male and female rats were trained to lever press for social access to another rat, and responding was evaluated after treatment with (a) intraperitoneal injection of dilute lactic acid (IP acid; 0.18-5.6%) administered alone as a visceral noxious stimulus, (b) the mu-opioid receptor (MOR) agonist morphine (0.32-10 mg/kg) or nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (10 mg/kg) administered alone, or (c) morphine or ketoprofen administered before IP acid. For comparison, the same treatments were evaluated in separate rats trained to lever press for food delivery. RESULTS: Both IP acid alone and morphine alone more potently decreased responding maintained by social interaction than by food, whereas ketoprofen did not affect responding for either reinforcer. In general, analgesics were most effective to rescue operant responding when relatively low IP acid concentrations produced significant but submaximal behavioral depression; however, morphine was not effective to rescue responding for social interaction. CONCLUSIONS: Operant responding maintained by social interaction was more sensitive to pain-related disruption and less responsive to opioid analgesic rescue than food-maintained operant responding. Social behavior may be especially vulnerable to depression by pain states.

Resistance of Food-Maintained Operant Responding to Mechanical Punishment in Rats: Further Evidence for Weak "Affective/Motivational Pain" in Rat Models of Inflammatory and Neuropathic Pain.

Clinically relevant chronic pain is often associated with functional impairment and behavioral depression as an "affective/motivational" sign of pain; however preclinical animal models of inflammatory and neuropathic pain often produce weak evidence of impaired function. We hypothesized that hindpaw mechanical stimulation produced by a requirement to rear on a textured "NOX" plate would punish operant responding in rats treated with intraplantar complete Freund's adjuvant (CFA, a model of inflammatory pain) or the chemotherapeutic paclitaxel (PTX, a model of neuropathic pain) and produce sustained pain-related depression of operant behavior. Male Sprague-Dawley rats were trained under a progressive-ratio (PR) schedule of food-maintained operant responding, then treated with CFA (100 µL in left hindpaw), PTX (2.0 mg/kg IP on alternate days for four total injections; 6.6 mg/kg IV on alternate days for three total injections), or saline vehicle. PR break points and mechanical thresholds for paw withdrawal from von Frey filaments were then tracked for 28 days. Subsequently, rats were tested with the opioid receptor antagonist naltrexone to assess latent sensitization and with the kappa opioid receptor (KOR) agonist U69593 to assess KOR function. CFA produced significant mechanical hypersensitivity for 3 weeks but decreased PR breakpoints for only 1 day. Both IP and IV PTX produced mechanical hypersensitivity for at least three weeks; however, only IV PTX decreased PR breakpoints, and this decrease was not alleviated by morphine. After recovery, naltrexone reinstated mechanical hypersensitivity in CFA- but not PTX-treated rats, and it did not reinstate depression of breakpoints in any group. U69593 dose-dependently decreased PR breakpoints in all groups with no difference between control vs. CFA/PTX groups. These results suggest that rearing on a textured NOX plate was not sufficient to punish operant responding in CFA- and PTX-treated rats despite the presence of sustained mechanical hypersensitivity. The rapid recovery of operant responding could not be attributed to latent sensitization, KOR downregulation, or behavioral tolerance. These results extend the range of conditions under which putative chronic pain manipulations produce weak evidence for depression of operant responding as a sign of the "affective/motivational" component of pain in rats.

Self-administration and behavioral economics of second-generation synthetic cathinones in male rats.

RATIONALE: Synthetic cathinones have become increasingly available as drugs of abuse. Distribution of these drugs is made possible by altering the chemical structures of prohibited cathinones and marketing them under misleading labels. Very little is known about the relative reinforcing effectiveness of new synthetic cathinones relative to known drugs of abuse. OBJECTIVE: We examined self-administration of three second-generation synthetic cathinones: alpha-pyrrolidinopentiophenone (alpha-PVP), 4-methyl-N-ethylcathinone (4-MEC), and 4-methyl-alpha-pyrrolidinopropiophenone (4-MePPP) relative to methamphetamine. METHOD: Male, Sprague-Dawley rats, implanted with intravenous catheters, were trained to self-administer methamphetamine (0.05 mg/kg/injection) under a fixed-ratio schedule. Following training, various doses of methamphetamine (0.006-0.1 mg/kg/injection), alpha-PVP (0.0015-0.1 mg/kg/injection), 4-MEC (0.1-3.2 mg/kg/injection), or 4-MePPP (0.1-0.8 mg/kg/injection) were available for self-administration in separate groups, followed by a behavioral-economics evaluation of the reinforcing effectiveness of each drug. RESULTS: For all drugs, at least one dose functioned as a reinforcer. Alpha-PVP and 4-MePPP maintained the highest numbers of infusions per session and both were more effective reinforcers relative to methamphetamine. 4-MEC and methamphetamine were not significantly different in terms of infusions per session or reinforcing effectiveness. CONCLUSION: Emerging synthetic cathinones whose primary pharmacological mechanism is to block dopamine uptake but with little effects on monoamine release or serotonin uptake may have a greater degree of abuse potential compared with known abused stimulants.

Institutional ethnography: explicating the social organization of professional health practices intending client empowerment.

Institutional enthnography uses traditional ethnographic procedures grounded in an analytic approach for explicating the social organization of knowledge. I illustrate the theory and method by describing my experience and analysis-to-date in a study of the social organization of knowledge in mental health, day program occupational therapy in Atlantic Canada. I emphasize the research standpoint within everyday experience. From this point, the researcher explicates (through description) how (micro) social relations, i.e. everyday actions, speech and documentation, are embedded in the (macro) practices of "institutions" such as mental health services. I summarize data management procedures including use of ETHNOGRAPH. Analysis-to-date is showing how the organization of mental health day programs both constrains and creates potential for occupational therapists enabling client empowerment.