The mu/kappa agonist nalbuphine attenuates sensitization to the behavioral effects of cocaine

• Published in: Pharmacology, biochemistry and behavior Vol. 104; pp. 40 - 46
• Main Authors: Smith, M.A., Cole, K.T., Iordanou, J.C., Kerns, D.C., Newsom, P.C., Peitz, G.W., Schmidt, K.T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2013
• Subjects: Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Cocaine; Cocaine - administration & dosage; Cocaine-Related Disorders - drug therapy; Cocaine-Related Disorders - physiopathology; Cocaine-Related Disorders - psychology; Drug Tolerance; Fixed ratio; Locomotor; Male; Motor Activity - drug effects; Motor Activity - physiology; Nalbuphine; Nalbuphine - administration & dosage; Progressive ratio; Rats; Rats, Long-Evans; Receptors, Opioid, kappa - agonists; Receptors, Opioid, kappa - physiology; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - physiology; Reinforcement (Psychology); Self Administration; Sensitization; Self-administration; Progressive ratio; Cocaine; Sensitization; Locomotor; Fixed ratio; Nalbuphine
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2012.12.026

Sensitization refers to an increase in sensitivity to a drug and is believed to play a role in the etiology of substance use disorders. The purpose of the present study was to evaluate the ability of the mixed mu/kappa agonist nalbuphine to modulate sensitization to the locomotor and positive reinforcing effects of cocaine. Rats were habituated to a locomotor activity chamber and treated with saline (1.0ml/kg, ip), cocaine (10mg/kg, ip), or cocaine+nalbuphine (10mg/kg, ip) every day for 10days. Following locomotor activity testing, rats were implanted with intravenous catheters and cocaine self-administration was examined on fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. Rats treated with cocaine exhibited a progressive increase in locomotor activity over the 10-day treatment period, and this effect was significantly reduced in rats treated with cocaine+nalbuphine. In self-administration tests, rats treated with cocaine exhibited significantly higher levels of responding at a threshold dose of cocaine (0.03mg/kg/infusion) on both FR and PR schedules than rats treated with saline. This increase in responding at a threshold dose of cocaine was blocked completely in rats treated with cocaine+nalbuphine. These data suggest that nalbuphine attenuates the development of sensitization to the behavioral effects of cocaine. ► Nalbuphine’s ability to reduce cocaine-induced sensitization was examined. ► Nalbuphine attenuated the increase in locomotor activity induced by cocaine. ► Nalbuphine blocked sensitization to the positive reinforcing effects of cocaine.