Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration

We characterized spontaneous and mecamylamme-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 mimpumps. Nicotine self-administration was studied before and after the induction of dependence. The initial test revealed significant nicotine self-administration at the 0.048 mug/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. (C) 2003 Elsevier B.V All rights reserved.