title: Pre-exposure to related substances induced place preference and self-administration of the NMDA receptor antagonist-benzodiazepine combination, zoletil.
abstract: Previously, we have reported that the N-methyl-D-aspartate (NMDA) receptor antagonist-benzodiazepine veterinary anesthetic combination, zoletil, produced reward and reinforcement, but only in rats repeatedly pretreated with the drug and not in drug-naïve rats. Therefore, we hypothesized that previous drug exposure plays an important role in the abuse of zoletil. In the present study, we examined whether pre-exposure to related substances, NMDA receptor antagonists (tiletamine, ketamine), and benzodiazepines (zolazepam, diazepam) predisposes animals to abuse zoletil. We examined whether animals repeatedly pretreated with tiletamine, ketamine, zolazepam, or diazepam, for 14 days, would show locomotor activation, place preference, and self-administration in response to zoletil. Place preference was observed in groups pretreated with either an NMDA receptor antagonist (ketamine) or a benzodiazepine (diazepam). However, locomotor activation and self-administration were only observed in rats pretreated with NMDA receptor antagonists (tiletamine and ketamine). These results show that pre-exposure to related substances might have induced neurobiological changes that consequently led to the expression of the rewarding and reinforcing effects of zoletil. This provides evidence that zoletil may be used as a substitute drug by abusers of NMDA receptor antagonists or benzodiazepines.
authors.affiliation: Department of Pharmacy, Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul, Republic of Korea.
authors.forename: June Bryan I
authors.initials: JB
authors.lastname: de la Peña
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Ike C
authors.initials: IC
authors.lastname: de la Peña
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Lee
authors.forename: Irene Joy
authors.initials: IJ
authors.lastname: I de la Peña
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000777:Anesthetics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D007649:Ketamine / Q000009:adverse effects / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D013037:Spatial Behavior / Q000187:drug effects*; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism; D013992:Tiletamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D015041:Zolazepam / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000777:Anesthetics; D004338:Drug Combinations; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C006131:tiletamine, zolazepam drug combination; D013992:Tiletamine; D007649:Ketamine; D015041:Zolazepam