Effects of training dose and two- versus three-choice testing procedure on nicotine discrimination responding in humans.

RATIONALE

Discrimination of a drug's interoceptive stimulus effects often depends substantially on training and testing conditions.

OBJECTIVES

We examined changes in nicotine discrimination behavior in humans as a function of lowering the training dose and of varying the discrimination testing procedure.

METHODS

Smokers and never-smokers (n=10 each) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0) and tested on generalization of discrimination responding across a range of doses from 0 to 20 microg/kg. Each subsequently learned to reliably discriminate progressively smaller doses of nicotine from placebo until his or her threshold dose for discrimination was identified (mean=2.7 microg/kg). A repeat testing of generalization responding across 0-20 microg/kg was then conducted, using placebo and the subject's threshold dose as training doses. Generalization testing involved both two-choice and three-choice (novel response option) quantitative procedures.

RESULTS

A significant shift to the left was seen in nicotine-appropriate responding in the two-choice procedure when the nicotine training dose was lowered (i.e. from the first to the second test of generalization). In the three-choice procedure, however, there was no such leftward shift. Instead, in never-smokers, a flattening of nicotine-appropriate responding occurred with a lowering of the training dose, while novel-appropriate responding significantly increased. The subjective effects of "head rush" and, in never-smokers only, "jittery" also showed a shift to the left in their relationship with nicotine generalization dose when the training dose was lowered.

CONCLUSIONS

These results confirm the importance of training and testing conditions on discrimination behavior and subjective drug responses within subjects and demonstrate the utility of the novel-response, three-choice procedure for assessing qualitatively different stimulus effects of novel drug doses.