title: Pregabalin role in inhibition of morphine analgesic tolerance and physical dependency in rats.
abstract: Pregabalin is recently proposed as analgesic or adjuvant in pain management. While previous preclinical investigations have evaluated pregabalin-opioid interactions, the effect of pregabalin on opioid tolerance and dependency has not yet been studied. Here we evaluated the effects of different doses of pregabalin (50, 100 and 200mg/kg, s.c.) on morphine-induced tolerance and dependency in rats. Adult male Wistar rats were rendered tolerant to analgesic effect of morphine by injection of morphine (10mg/kg, s.c.) twice daily for 7 days. To develop morphine dependence, rats were given escalating doses of morphine. To determine the effect of pregabalin on the development of morphine tolerance and dependence, different doses of pregabalin were administrated before morphine. The tail-flick and naloxone precipitation withdrawal tests were used to evaluate the degree of tolerance and dependence, respectively. Chronic morphine-injected rats showed significant decrements in the percentage maximum possible effect (%MPE) of morphine on the days 5 and 7 (32.5%±3.5, 21.5%±4, respectively) compared to the first day (100%) which showed morphine tolerance. Pregabalin 200mg/kg completely prevented the development of morphine tolerance. In addition, concomitant treatment of morphine with pregabalin attenuated almost all of the naloxone-induced withdrawal signs which include weight loss, jumping, penis licking, teeth chattering, wet dog shakes, rearing, standing, sniffing, face grooming and paw tremor. These data show that pregabaline has a potential anti-tolerant/anti-dependence property against chronic usage of morphine. Therefore, pregabalin appears to be a promising candidate for the treatment of opioid addiction after confirming by future clinical studies.
authors.affiliation: Department of Biology, School of Basic Sciences, Bu-Ali Sina University, 65178-33391 Hamedan, Iran. Electronic address: p.hasanein@basu.ac.ir.
authors.forename: Parisa
authors.initials: P
authors.lastname: Hasanein
authors.affiliation: Department of Biology, School of Basic Sciences, Bu-Ali Sina University, 65178-33391 Hamedan, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Shakeri
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D000069583:Pregabalin; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D009020:Morphine
keywords: Dependency; Morphine; Pregabalin; Rats; Tolerance