Date of Award


Degree Name

Doctor of Philosophy



First Advisor

Dr. Alan D. Poling

Second Advisor

Dr. Lisa E. Baker

Third Advisor

Dr. Richard W. Malott

Fourth Advisor

Dr. Robert C. MacPhail


Tolerance has previously been shown to develop to nicotine's effects on operant behavior. This experiment explored whether tolerance would still develop when nicotine administrations were separated by three weeks. Anatoxin-a, a nicotinic-receptor agonist, was also tested and the results were compared to nicotine. Male Long Evans rats performed under a multiple VR30 VI30-sec food-reinforcement schedule. Phase I rats were divided into 6 groups of 8 that received four weekly subcutaneous injections of nicotine (0.0-1.8 mg/kg) and anatoxin-a (0-250 mcg/kg) prior to testing sessions. An ED50 was derived, for each compound, from the VR dose-response curve. Phase II rats were divided into 4 groups of 8 and received the nicotine (0.73 mg/kg) or anatoxin-a (92 μg/kg) ED50 either: each week for four weeks; during the first and fourth weeks only; during the last week only; or saline during all four weeks. A third phase was also included to explore whether performance changes with weekly exposures primarily reflected behavioral or pharmacological tolerance. When initially administered (Phase I), both compounds decreased response rates and reinforcement rates in both components of the multiple schedule. Substantial tolerance developed to the disruptive effects of both compounds with subsequent weekly administrations. Some tolerance developed to nicotine when administrations were separated by 3 weeks (Phase II), however, this was not true of the anatoxin-a results, which indicated that tolerance did not develop during this phase. The results of the third phase do not clearly indicate either pharmacological or behavioral tolerance. With regard to comparing nicotine and anatoxin-a, results indicate a substantial similarity in the behavioral effects of the two compounds with both acute and weekly administration. However, as the amount of time between administrations increases, there is less similarity in the behavioral effects of nicotine and anatoxin-a.

Access Setting

Dissertation-Open Access