Smoke extracts and nicotine, but not tobacco extracts, potentiate firing and burst activity of Ventral Tegmental Area dopaminergic neurons in mice

International audienceNicotine prominently mediates the behavioral effects of tobacco consumption, either through smoking or when taking tobacco by snuff or chew. However, many studies question the exclusive role of nicotine in these effects. The use of preparations containing all the components of tobacco, such as tobacco and smoke extracts, may be more suitable than nicotine alone to investigate the behavioral effects of smoking and tobacco intake. In the present study, the electrophysiological effects of tobacco and smoke on ventral tegmental area dopamine (DA) neurons were examined in vivo in anesthetized wild-type (WT), ß2 nicotinic acetylcholine receptor (nAChR) knock-out (ß2-/-), α4-/- and α6-/- mice and compared to those of nicotine alone. In WT mice, smoke and nicotine had similar potentiating effects on DA cells activity, but the action of tobacco on neuronal firing was weak, and often inhibitory. In particular, nicotine triggered strong bursting activity, while no bursting activity was observed after tobacco extract administration. In ß2-/- mice, nicotine or extract elicited no modification of the firing patterns of DA cells, indicating that extract act predominantly through nAChRs. The differences between DA cells activation profiles induced by tobacco and nicotine alone observed in WT persited in α6-/- mice but not in α4-/- mice. These results would suggest that tobacco has lower addiction generating properties compared to either nicotine alone or smoke. The weak activation and prominent inhibition obtained with tobacco extracts suggest that tobacco contains compounds which counteract some of the activating effects of nicotine and promote inhibition on DA cell acting through α4ß2*-nAChRs. The nature of these compounds remains to be elucidated. It nevertheless confirms that nicotine is the main substance involved in the tobacco addiction-related activation of mesolimbic DA neurons