THE DEVELOPMENT OF TOLERANCE TO NICOTINE BY RATS

¹ From the Laboratories of Pharmacology, University of Oregon and University of Southern California

Young and adult rats were injected twice daily with nicotine for from three to seven months, and the following observations made.

1. A definite tolerance to the minimal effective dose and minimal convulsive dose was demonstrated in the young rats.

2. The adult rats failed to develop a tolerance to nicotine.

3. The young rats did not develop a tolerance to the fatal dose of nicotine.

4. All rats, young and adult, developed a conditioned salivary reflex to nicotine.

5. The conditioned reflex in the young rats was later extinguished but in the adult rats, the conditioned reflex persisted.

6. It is suggested that the tolerance to small doses of nicotine, developed in young rats, may be conditioned inhibition, although the experimental results may be used also to support the view that the increased tolerance is due to decreased tissue susceptibility and increased destruction or excretion of the drug.