Cross-tolerance in drug response and differential changes in central nicotinic and N-methyl-d-aspartate receptor binding following chronic treatment with either (+)- or (–)-nicotine

Abstract 

The present study compared the effects of chronic treatment (21 days) with (+)-nicotine and (–)-nicotine on exploratory behaviours and body temperature in rats. Chronic treatment with either (+)- or (–)-nicotine induced tolerance in exploratory behaviours. A cross-tolerance between the two stereoisomers was also observed. Body temperature was differentially affected by chronic (+)- and (–)-nicotine, but cross-tolerance was still observed. In addition, nicotinic acetylcholine receptor (nAChR) and N-methyl-d-aspartate (NMDA) receptor binding in rats treated with (+)- and (–)-nicotine were measured by receptor autoradiography. Chronic treatment with (+)- and (–)-nicotine significantly increased nAChR binding in different brain regions. Furthermore, significant differences in the induction of nAChR binding by chronic (+)- and (–)-nicotine were detected in several brain regions. Chronic treatment with (+)-nicotine significantly increased NMDA receptor binding in the CA1 region of the hippocampus. However, (–)-nicotine had no effect on NMDA receptor binding in any of the regions analysed. These results demonstrate differences between chronic treatment with (+)- and (–)-nicotine in physiological responses such as body temperature and biochemical changes such as changes in nAChRs and NMDA receptor binding, although a cross-tolerance between the two enantiomers in behaviour and body temperature is also observed.