Effect of acute and repeated nicotine administration on the electrical activity of the lateral habenular neurons in rats

Abstract

Tobacco smoking represents a well-known risk factor for health that still accounts for a high number of deaths. So far, existing smoking cessation therapies have not been proven very successful at quitting this habit and a better undrstanding of the neurobiology of tobacco dependence is still needed. Nicotine is the neuroactive compound contained in tobacco that is responsible for its rewarding and reinforcing properties by acting on the midbrain dopaminergic system. The lateral habenula (LHb) is an epithalamic structure involved in pain, stress, depression and in encoding aversive stimuli. This structure is known to indirectly inhibit the DA system through the activation of the RMTg, a GABA-ergic area located at the back of the VTA. The RMTg receives a strong glutamatergic imput from the LHb and is activated by the systemic injection of nicotine in rats. Thus the LHb might represent a possible target for the action of nicotine. Our data shows that systemic administration of nicotine dose-dependently increases the activity of single LHb neurons recorded extracellularly in vivo in rats, particularly at high doses. Following two weeks of nicotine chronic treatment, this response is drastically decreased while after 1 day of withdrawal only low doses of nicotine are again able to significantly increase the firing activity of the LHb neurons compared to the control group. These evidences strongly suggest that the LHb might play an important role in mediating the effects of nicotine on the midbrain DA system thus participating to the mechanism of addiction to this drug.