Role of beta 4*Nicotinic Acetylcholine Receptors in the Habenulo-Interpeduncular Pathway in Nicotine Reinforcement in Mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Neuropsychopharmacology Année : 2016

Role of beta 4*Nicotinic Acetylcholine Receptors in the Habenulo-Interpeduncular Pathway in Nicotine Reinforcement in Mice

Résumé

Nicotine exerts its psychopharmacological effects by activating the nicotinic acetylcholine receptor (nAChR), composed of alpha and/or beta subunits, giving rise to a diverse population of receptors with a distinct pharmacology. beta 4-containing (beta 4*) nAChRs are located almost exclusively in the habenulo-interpeduncular pathway. We examined the role of beta 4* nAChRs in the medial halpenula (MHb) and the interpeduncular nucleus (IPN) in nicotine reinforcement using behavioral, electrophysiological, and molecular techniques in transgenic mice. Nicotine intravenous self-administration (IVSA) was lower in constitutive beta 4 knockout (KO) mice at all doses tested (7.5, 15, 30, and 60 mu g/kg/infusion) compared with wild-type (WT) mice. In vivo microdialysis showed that beta 4KO mice have higher extracellular dopamine (DA) levels in the nucleus accumbens than in WT mice, and exhibit a differential sensitivity to nicotine-induced DA outflow. Furthermore, electrophysiological recordings in the ventral tegmental area (VTA) demonstrated that DA neurons of beta 4KO mice are more sensitive to lower doses of nicotine than that of WT mice. Re-expression of beta 4* nAChRs in IPN neurons fully restored nicotine IVSA, and attenuated the increased sensitivity of VTA DA neurons to nicotine. These findings suggest that beta 4* nAChRs in the IPN have a role in maintaining nicotine IVSA.

Dates et versions

hal-01542255 , version 1 (19-06-2017)

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Citer

Lauriane Harrington, Xavier Vinals, Andrea Herrera-Solis, Africa Flores, Carole Morel, et al.. Role of beta 4*Nicotinic Acetylcholine Receptors in the Habenulo-Interpeduncular Pathway in Nicotine Reinforcement in Mice. Neuropsychopharmacology, 2016, 41 (7), pp.1790-1802. ⟨10.1038/npp.2015.346⟩. ⟨hal-01542255⟩
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