title: The anxiolytic-like effect of nicotine undergoes rapid tolerance in a model of contextual fear conditioning in rats.
abstract: The effects of repeated administration of nicotine on contextual fear conditioning, locomotor activity, and pain threshold, were examined in rats. It was found that a single injection of nicotine prior to the training session (three 0.7-mA footshocks, each 0.5 s long), decreased the freezing reaction during the retest 24 h later. The locomotor activity was moderately enhanced, and the pain threshold remained unchanged. The baseline freezing measured immediately after administration of a single dose of nicotine was not significantly different from the saline-treated group. The anxiolytic-like effect of nicotine was as potent as that of midazolam, a benzodiazepine derivative. After five day-by-day injections, the anxiolytic-like effect of nicotine (0.6 mg/kg, sc) was no longer present, independently whether the last drug injection was given 24 h or 5 min (i.e., the sixth, additional, nicotine injection), prior to the training session. Thus, it appeared that the expression of tolerance to the nicotine-induced anxiolytic-like action did not require a direct stimulation of nicotinic receptors. Simultaneously, in this group of animals, nicotine caused a potent stimulation of locomotor activity in the open field test. The applied dosage and regimen of nicotine administration did not change rat pain threshold (flinch-jump test). Collectively, the present data showed for the first time, that short-term, intermittent, administration of nicotine was sufficient to induce tolerance to the anxiolytic-like effect of this drug, in the model of fear conditioning to context. Importantly, a clear dissociation between the locomotor and anxiolytic-like effects of nicotine was present. This effect appeared independent also of changes in rat pain threshold. The possible mechanisms of this phenomenon are discussed.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, Krakowskie Przedmieście 26/28, 00-927, Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Szyndler
authors.forename: H
authors.initials: H
authors.lastname: Sienkiewicz-Jarosz
authors.forename: P
authors.initials: P
authors.lastname: Maciejak
authors.forename: M
authors.initials: M
authors.lastname: Siemiatkowski
authors.forename: D
authors.initials: D
authors.lastname: Rokicki
authors.forename: A I
authors.initials: AI
authors.lastname: Członkowska
authors.forename: A
authors.initials: A
authors.lastname: Płaznik
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014151:Anti-Anxiety Agents; D018722:Nicotinic Agonists; D009538:Nicotine