Olfactory and trigeminal responses to nicotine

Abstract

Olfactory and trigeminal sensitivities to vapor-phase nicotine were assessed by using psychophysical studies with normal and anosmic human subjects and using electrophysiological studies with rats and pigeons. This work showed that 1) psychophysical estimates of sensitivity are approximately tenfold higher (i.e., lower thresholds) than those based on neural recordings, with both techniques demonstrating greater olfactory than trigeminal sensitivity for nicotine and other compounds; 2) for both chemosensory inputs, sensitivity to nicotine is at least 30-fold greater than that to several other compounds; 3) human subjects can discriminate qualitatively between the S-(−) and the R-(−) stereoisomers of nicotine, although the relative importance of olfactory and trigeminal inputs in this discriminative ability is unclear; and 4) trigeminal nerve responses in rats show similar thresholds for S-(−)- and R-(+)-nicotine but show lower suprathreshold responses to the R-(+) stereoisomer. The olfactory epithelium and trigeminal ganglion exhibit high-affinity binding of S-(−)-nicotine. In addition, reverse transcriptase-polymerase chain reaction (RT-PCR) studies have shown that many of the nicotinic acetylcholine receptor (nAChR) subunits found in other parts of the nervous system are present in the olfactory epithelium and bulb and in the trigeminal ganglion. Collectively, these findings suggest that two or more of the types of nAChRs identified in other parts of the nervous system may serve as receptor proteins that bind nicotine-like odorants or irritants. Investigation of the pharmacology of chemosensory responses to nicotine may help to establish causal links between specific receptor proteins and the perception of odor and irritation. Drug Dev. Res. 38:160–168 © 1996 Wiley-Liss, Inc.