Nicotine modulation of the lateral habenula/ventral tegmental area circuit dynamics: An electrophysiological study in rats
Neuropharmacology. 2022-01-01; 202: 108859
DOI: 10.1016/J.NEUROPHARM.2021.108859
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1. Neuropharmacology. 2022 Jan 1;202:108859. doi: 10.1016/j.neuropharm.2021.108859.
Epub 2021 Oct 26.
Nicotine modulation of the lateral habenula/ventral tegmental area circuit
dynamics: An electrophysiological study in rats.
Pierucci M(1), Delicata F(2), Colangeli R(2), Marino Gammazza A(3), Pitruzzella
A(3), Casarrubea M(4), De Deurwaerdère P(5), Di Giovanni G(6).
Author information:
(1)Laboratory of Neurophysiology, Department of Physiology and Biochemistry,
Faculty of Medicine and Surgery, University of Malta, Msida, Malta. Electronic
address: .
(2)Laboratory of Neurophysiology, Department of Physiology and Biochemistry,
Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
(3)Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced
Diagnosis BIND, University of Palermo, Palermo, Italy.
(4)Laboratory of Behavioral Physiology, Human Physiology Section Giuseppe Pagano,
Department of Biomedicine, Neuroscience and Advanced Diagnosis BIND, University
of Palermo, Palermo, Italy.
(5)Centre National de la Recherche Scientifique Unité Mixte de Recherche, 5287,
Bordeaux Cedex, France.
(6)Laboratory of Neurophysiology, Department of Physiology and Biochemistry,
Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Neuroscience
Division, School of Biosciences, Cardiff University, Cardiff, UK. Electronic
address: .
Nicotine, the addictive component of tobacco, has bivalent rewarding and aversive
properties. Recently, the lateral habenula (LHb), a structure that controls
ventral tegmental area (VTA) dopamine (DA) function, has attracted attention as
it is potentially involved in the aversive properties of drugs of abuse.
Hitherto, the LHb-modulation of nicotine-induced VTA neuronal activity in vivo is
unknown. Using standard single-extracellular recording in anesthetized rats, we
observed that intravenous administration of nicotine hydrogen tartrate
(25-800 μg/kg i.v.) caused a dose-dependent increase in the basal firing rate of
the LHb neurons of nicotine-naïve rats. This effect underwent complete
desensitization in chronic nicotine (6 mg/kg/day for 14 days)-treated animals. As
previously reported, acute nicotine induced an increase in the VTA DA neuronal
firing rate. Interestingly, only neurons located medially (mVTA) but not
laterally (latVTA) within the VTA were responsive to acute nicotine. This pattern
of activation was reversed by chronic nicotine exposure which produced the
selective increase of latVTA neuronal activity. Acute lesion of the LHb,
similarly to chronic nicotine treatment, reversed the pattern of DA cell
activation induced by acute nicotine increasing latVTA but not mVTA neuronal
activity. Our evidence indicates that LHb plays an important role in mediating
the effects of acute and chronic nicotine within the VTA by activating distinct
subregional responses of DA neurons. The LHb/VTA modulation might be part of the
neural substrate of nicotine aversive properties. By silencing the LHb chronic
nicotine could shift the balance of motivational states toward the reward.
Copyright © 2021 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.neuropharm.2021.108859
PMID: 34710468 [Indexed for MEDLINE]