Sensitization and tolerance with episodic (weekly) nicotine on motor activity in rats.
Nicotine's effects on motor activity have been studied extensively. Sensitization or tolerance can develop to nicotine's acute effects with daily exposure. Limited data indicate that sensitization can also develop when nicotine is given less frequently than daily. The present experiments were designed to extend this finding and to more fully characterize the effects of nicotine on motor activity when given at weekly intervals. In both experiments, the horizontal and vertical activity of adult female Long-Evans (LE) rats was recorded in photocell chambers. In Experiment 1, either saline or nicotine hydrogen tartrate (0.3, 0.6, 1.2 or 1.8 mg of salt/kg BW, s.c.) was administered once each week to rats that were tested daily (M-F). Acute nicotine administration produced no significant effect on horizontal activity at lower doses, while the highest dose produced a decrease (ca. 30%). Substantial and significant dose-related decreases in vertical activity were also obtained initially. Weekly dosing produced tolerance to nicotine's decreasing effects on vertical activity and increases (i.e., sensitization) in horizontal activity at all doses, and these effects persisted for at least 3 weeks. Experiment 2 partially replicated the results of Experiment 1 and indicated further that small sequential dose variations generally had little influence on nicotine tolerance and sensitization. The present results on horizontal activity extend prior findings of sensitization to weekly nicotine to include a broad range of doses. Results also showed that tolerance, but not sensitization, occurred to nicotine's effects on vertical activity over a comparable dose range. Further research is warranted on the importance of episodic, or recurring intermittent exposures in determining nicotine's effects, and those of other nicotinic agents, on behavior.
MacPhail
R C
RC
Neurotoxicology Division, B105-03, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. macphail.robert@epa.gov
Farmer
J D
JD
Jarema
K A
KA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans
D018722:Nicotinic Agonists; D009538:Nicotine