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Effects of training dose and two- versus three-choice testing procedure on nicotine discrimination responding in
K A Perkins1, C Fonte, M Sanders
1Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. kperkins@vms.cis.pitt.edu
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.