title: Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement.
abstract: Smoking is the most important preventable cause of mortality and morbidity worldwide. This nicotine addiction is mediated through the nicotinic acetylcholine receptor (nAChR), expressed on most neurons, and also many other organs in the body. Even within the ventral tegmental area (VTA), the key brain area responsible for the reinforcing properties of all drugs of abuse, nicotine acts on several different cell types and afferents. Identifying the precise action of nicotine on this microcircuit, in vivo, is important to understand reinforcement, and finally to develop efficient smoking cessation treatments. We used a novel lentiviral system to re-express exclusively high-affinity nAChRs on either dopaminergic (DAergic) or γ-aminobutyric acid-releasing (GABAergic) neurons, or both, in the VTA. Using in vivo electrophysiology, we show that, contrary to widely accepted models, the activation of GABA neurons in the VTA plays a crucial role in the control of nicotine-elicited DAergic activity. Our results demonstrate that both positive and negative motivational values are transmitted through the dopamine (DA) neuron, but that the concerted activity of DA and GABA systems is necessary for the reinforcing actions of nicotine through burst firing of DA neurons. This work identifies the GABAergic interneuron as a potential target for smoking cessation drug development.
authors: Département de Neuroscience, Institut Pasteur, Unité Neurobiologie intégrative des systèmes cholinergiques, Paris, France.
authors: S
authors: S
authors: Tolu
authors: R
authors: R
authors: Eddine
authors: F
authors: F
authors: Marti
authors: V
authors: V
authors: David
authors: M
authors: M
authors: Graupner
authors: S
authors: S
authors: Pons
authors: M
authors: M
authors: Baudonnat
authors: M
authors: M
authors: Husson
authors: M
authors: M
authors: Besson
authors: C
authors: C
authors: Reperant
authors: J
authors: J
authors: Zemdegs
authors: C
authors: C
authors: Pagès
authors: Y A H
authors: YA
authors: Hay
authors: B
authors: B
authors: Lambolez
authors: J
authors: J
authors: Caboche
authors: B
authors: B
authors: Gutkin
authors: A M
authors: AM
authors: Gardier
authors: J-P
authors: JP
authors: Changeux
authors: P
authors: P
authors: Faure
authors: U
authors: U
authors: Maskos
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology; D012054:Reinforcement, Psychology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine