Nicotine induced behavioral locomotor sensitization.
1. Nicotine behavioral sensitization of locomotor activity was investigated in adult female Sprague Dawley rats. Five different experiments were performed with nicotine in various doses of 0.1, 0.32, or 1.0 mg/kg i.p. These included: 1) effects of daily nicotine for 6 days, 2) effects of once per week nicotine for 3 weeks, 3) effects of MK-801 on nicotine-induced locomotor activity, 4) effects of dexamethasone on nicotine-induced locomotor activity, 5) induction of tolerance to nicotine-induced locomotor sensitization and lack of cross tolerance to caffeine. 2. Locomotor activity was measured with a photoelectric computerized system. The first dose of nicotine (0.32 mg/kg) induced marked locomotor depression. Once daily injection of 0.32 mg/kg of nicotine for 6 days produced tolerance to its depressant effects and sensitized the rats to its stimulant effects. Three once weekly doses of 0.32 mg/kg of nicotine also produced tolerance to its depressant effects and some locomotor stimulation. 3. Daily pretreatment for 5 days with a dose of 0.18 mg/kg of MK-801 i.p. partially antagonized the locomotor depressant and stimulant actions of nicotine. 4. Dexamethasone (1 mg/kg i.p.) daily pretreatment barely reduced nicotine locomotor depression and only very slightly enhanced locomotor stimulation. 5. Accumulating doses of 0.32 and 1.0 mg/kg b.i.d. of nicotine produced tolerance to its locomotor stimulant effects in rats previously sensitized to 0.32 mg/kg. There was no cross-tolerance to 32 mg/kg of caffeine citrate in previously sensitized animals tolerant to the stimulant effects of nicotine.
Department of Pharmacology, University of Michigan, Ann Arbor, 48109-0632, USA. efdabcde@umich.edu
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002110:Caffeine; D016291:Dizocilpine Maleate; D009538:Nicotine; D003907:Dexamethasone