title: Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration.
abstract: We characterized spontaneous and mecamylamine-precipitated nicotine withdrawal using intravenous nicotine self-administration, the acoustic startle response, prepulse inhibition and somatic signs of withdrawal in DBA/2J mice. Nicotine dependence was induced by continuous nicotine infusion through osmotic minipumps. Nicotine self-administration was studied before and after the induction of dependence. The initial test revealed significant nicotine self-administration at the 0.048 microg/infusion dose. During the second self-administration test, saline-treated mice exhibited increased aversiveness of response-contingent infusions of high nicotine doses; these changes were not seen in the nicotine-treated animals reflecting tolerance to nicotine's effects. Neither mecamylamine administration nor spontaneous withdrawal affected the expression of somatic signs, except that increases in jumping were observed during spontaneous withdrawal. Finally, nicotine withdrawal increased general activity in the startle chambers when no stimuli were presented, possibly reflecting increased body tremor and/or agitation, and decreased prepulse inhibition reflecting a sensorimotor gating deficit; the last two effects were reversed by nicotine self-administration. Thus, nicotine withdrawal results in modest, but yet detectable, changes in the behavior of mice.
authors.affiliation: Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Semenova
authors.forename: Anton
authors.initials: A
authors.lastname: Bespalov
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D007275:Injections, Intravenous; D008297:Male; D008464:Mecamylamine / Q000627:therapeutic use; D051379:Mice; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000627:therapeutic use; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine