Biphasic dose-related responses of the CNV (contingent negative variation) to I.V. nicotine in man

Abstract

1 The effects of intravenous injections of nicotine bitartrate, given as intermittent `shots', on the magnitude of the contingent negative variation (CNV) were studied in twelve male volunteers.

2 In one series of experiments in five subjects, a fixed dose of nicotine was used. In three of these subjects nicotine 500 μg or 750 μg produced a reproducible increase in magnitude of the CNV. In two subjects nictone 750 μg produced a reproducible decrease in magnitude of the CNV. The direction and magnitude of the CNV changes could be reproduced by cigarette smoking.

3 In another series of experiments in eight subjects, dose-response relationships for the effect of nicotine on the CNV were measured using a range of doses from 12.5 to 800 μg. Individual and mean dose-response curves were found to be biphasic so that whilst smaller doses produced an increase of CNV magnitude (stimulant effect), larger doses produced a decrease of the CNV (depressant effect).

4 The results are discussed in relation to the possible mechanism of action on the brain of nicotine as obtained by inhaling cigarette smokers.