title: Pre-exposure to ethanol, but not to caffeine and nicotine, induced place preference and self-administration of the NMDA receptor antagonist-benzodiazepine combination, Zoletil®.
abstract: Zoletil® is an equal amount combination of the NMDA receptor antagonist, tiletamine, and the benzodiazepine, zolazepam, usually used as a veterinary anesthetic. Previous studies have shown that pre-exposure to Zoletil® and other psychoactive drugs (e.g. ketamine, diazepam) plays a significant role in the abuse liability of the compound. However, these studies were only focused on illicit psychoactive drugs and not on the more widely used licit psychoactive substances. Thus, the goal of the present work is to investigate whether pre-exposure to the three most commonly used licit psychoactive substances (caffeine, nicotine, and ethanol) affects the rewarding and reinforcing effects of Zoletil®. Rats were pretreated with caffeine (1.25 or 2.5 mg/kg), nicotine (125 or 250 μg/kg), ethanol (0.5, 2, or 4 g/kg), or saline (1 ml/kg) for 14 days, and evaluated for subsequent Zoletil® place preference (2.5 mg/kg) and self-administration (250 μg/kg). Zoletil® produced neither place preference nor self-administration in saline-pretreated rats. Pre-exposure to caffeine or nicotine does not have significant effects on Zoletil®'s abuse potential. However, pretreatment of ethanol significantly produced Zoletil® place preference and self-administration. These results suggest that individuals who are exposed to ethanol may have a high propensity to use/abuse Zoletil®. More importantly, the present result advocates the careful monitoring on the use and dispensation of Zoletil® or related substances.
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 26-21 Kongneung-2-dong, Nowon-gu, Seoul 139-742, Republic of Korea.
authors.forename: June Bryan I
authors.initials: JB
authors.lastname: de la Peña
authors.forename: Irene Joy I
authors.initials: IJ
authors.lastname: dela Peña
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Lee
authors.forename: Ike
authors.initials: I
authors.lastname: dela Peña
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Aee Ree
authors.initials: AR
authors.lastname: Sohn
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000777:Anesthetics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D003216:Conditioning, Operant; D004338:Drug Combinations; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013992:Tiletamine / Q000008:administration & dosage / Q000494:pharmacology*; D015041:Zolazepam / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000777:Anesthetics; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; C006131:tiletamine, zolazepam drug combination; D001569:Benzodiazepines; D013992:Tiletamine; D002110:Caffeine; D000431:Ethanol; D009538:Nicotine; D015041:Zolazepam
keywords: Addiction; Alcohol; Conditioned place preference; Drug abuse; Self-administration; Zoletil