Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (UMR5287)

Aquitaine Institute for Cognitive and Integrative Neuroscience

Université de Bordeaux

Zone nord Bat 2 2ème étage
146, rue Léo Saignat
33076 Bordeaux cedex


Supervisory authorities

CNRS Ecole Pratique des Hautes Etudes Université de Bordeaux

Our partners

Neurocampus Unitéde Formation de Biologie


GDR Robotique GDR Mémoire GDR Multi-électrodes


Home > News

Little known beta4 nicotinic cholinergic receptors play in fact an essential role in reward processes and nicotine’s addictive properties

by Loïc Grattier - published on , updated on

 Little known beta4 nicotinic cholinergic receptors play in fact an essential role in reward processes and nicotine's addictive properties

Husson M, Harrington L, Tochon L, Cho Y, Ibañez-Tallon I, Maskos U, David V.β4-Nicotinic Receptors Are Critically Involved in Reward-Related Behaviors and Self-Regulation of Nicotine Reinforcement. J Neurosci. 2020 Apr 22;40(17):3465-3477. doi: 10.1523/JNEUROSCI.0356-19.2020.

This article was recently awarded with a F1000 recommendation for exceptional importance:

Nicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in the CHRNA5-CHRNA3-CHRNΒ4 gene cluster, coding for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChR) subunits, to nicotine addiction. β4*nAChRs have been implicated in nicotine withdrawal. Here we show that β4*nAChRs also are involved in non-nicotine mediated responses that may predispose to addiction-related behaviors. β4 knock-out (KO) male mice show increased novelty-induced locomotor activity, lower baseline anxiety, and motivational deficits in operant conditioning for palatable food rewards and Go/No-go tasks. To further explore reward deficits we used intracranial self-administration (ICSA) by injecting nicotine directly into the ventral tegmental area (VTA) in mice. We found that, at low nicotine doses, β4KO self-administer less than wild-type (WT) mice. Conversely, at high nicotine doses, this was reversed and β4KO self-administered more than WT mice, whereas β4-overexpressing mice avoided nicotine injections. Viral expression of β4 subunits in medial habenula (MHb), interpeduncular nucleus (IPN), and VTA of β4KO mice revealed dose- and region- dependent differences: β4*nAChRs in the VTA potentiated nicotine-mediated rewarding effects at all doses, whereas β4*nAChRs in the MHb-IPN pathway limited VTA-ICSA at high nicotine doses. Together, our findings indicate that the lack of functional β4*nAChRs result in deficits in reward sensitivity, including increased ICSA at high doses of nicotine. Normal, WT levels of nicotine ICSA are restored by re-expression of β4*nAChRs in the MHb-IPN. These data indicate that the β4 subunit is a critical modulator of reward-related behaviors, and that β4*nAChRs may provide a promising novel drug target for smoking cessation.