A concurrent excitation and inhibition of dopaminergic subpopulations in response to nicotine

Eddine, Raphaël; Valverde, Sébastien; Tolu, Stefania; Dautan, Daniel; Hay, Y. Audrey; Morel, Carole; Cui, Yihui; Lambolez, Bertrand; Venance, Laurent; Marti, Fabio; Fauré, Philippe

doi:10.1038/srep08184

Cited by 31 publications

(44 citation statements)

References 39 publications

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“…S1a) (∆Frequency: One-way ANOVA, F (4, 72) = 10.9, p < 0.001; ∆%SWB: Kruskal-Wallis, X 2 = 10.5, df = 4, p < 0.05). Similarly to what we observed with nicotine24, a fraction of VTA DA cells were inhibited by alcohol, but the current study focuses on cells that were excited by alcohol.…”

Section: Resultsmentioning

confidence: 70%

Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors

Tolu

Marti

Morel

et al. 2017

Sci Rep

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Alcohol and nicotine are the most widely co-abused drugs. Both modify the activity of dopaminergic (DA) neurons of the Ventral Tegmental Area (VTA) and lead to an increase in DA release in the Nucleus Accumbens, thereby affecting the reward system. Evidences support the hypothesis that distinct nicotinic acetylcholine receptors (nAChRs), the molecular target of acetylcholine (ACh) and exogenous nicotine, are also in addition implicated in the response to alcohol. The precise molecular and neuronal substrates of this interaction are however not well understood. Here we used in vivo electrophysiology in the VTA to characterise acute and chronic interactions between nicotine and alcohol. Simultaneous injections of the two drugs enhanced their responses on VTA DA neuron firing and chronic exposure to nicotine increased alcohol-induced DA responses and alcohol intake. Then, we assessed the role of β4 * nAChRs, but not β2 * nAChRs, in mediating acute responses to alcohol using nAChR subtypes knockout mice (β2−/− and β4−/− mice). Finally, we showed that nicotine-induced modifications of alcohol responses were absent in β2−/− and β4−/− mice, suggesting that nicotine triggers β2* and β4 * nAChR-dependent neuroadaptations that subsequently modify the responses to alcohol and thus indicating these receptors as key mediators in the complex interactions between these two drugs.

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Section: Resultsmentioning

confidence: 70%

Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors

Tolu

Marti

Morel

et al. 2017

Sci Rep

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“…The functional diversity of VTA neurons has been constantly updated (Unlgess, 2004; Stamatakis et al, 2013; Root et al, 2014b; Mejias-Aponte et al, 2015; Eddine et al, 2015; Kotecki et al, 2015; Beier et al, 2015). As detailed above, the multiplexed neurotransmission of the VTA-VGluT2 neurons is an emerging factor involved in the complexity of VTA function.…”

Section: Functional Diversity By Vta Neuronsmentioning

confidence: 99%

“…Indeed, many studies have reported heterogeneous responses of specific VTA neurons (Brischoux et al, 2009; Borgkvist et al, 2011; Margolis et al, 2014; Eddine et al, 2015; Mrejeru et al 2015; Mejias-Aponte et al, 2015), and it would seem likely that this diversity is due (at least in part) to cells that are capable of multiplexed neurotransmission. With this in mind, it is clear that that the discovery of compound cell types has wide-reaching implications for our understanding of VTA circuit functions.…”

Section: Multiplexed Transmission: Future Directions and Consideratiomentioning

confidence: 99%

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

Barker

Root

Zhang

et al. 2016

Journal of Chemical Neuroanatomy

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The ventral tegmental area (VTA) is an evolutionarily conserved structure that has roles in reward-seeking, safety-seeking, learning, motivation, and neuropsychiatric disorders such as addiction and depression. The involvement of the VTA in these various behaviors and disorders is paralleled by its diverse signaling mechanisms. Here we review recent advances in our understanding of neuronal diversity in the VTA with a focus on cell phenotypes that participate in ‘multiplexed’ neurotransmission involving distinct signaling mechanisms. First, we describe the cellular diversity within the VTA, including neurons capable of transmitting dopamine, glutamate or GABA as well as neurons capable of multiplexing combinations of these neurotransmitters. Next, we describe the complex synaptic architecture used by VTA neurons in order to accommodate the transmission of multiple transmitters. We specifically cover recent findings showing that VTA multiplexed neurotransmission may be mediated by either the segregation of dopamine and glutamate into distinct microdomains within a single axon or by the integration of glutamate and GABA into a single axon terminal. In addition, we discuss our current understanding of the functional role that these multiplexed signaling pathways have in the lateral habenula and the nucleus accumbens. Finally, we consider the putative roles of VTA multiplexed neurotransmission in synaptic plasticity and discuss how changes in VTA multiplexed neurons may relate to various psychopathologies including drug addiction and depression.

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“…). Further investigations define a D 2 ‐receptor dependent inhibition, opening the question on the role of these neurons in nicotine reinforcement (Eddine et al., ).…”

Section: Reinforcing Properties Of Nicotine and Subsequent Neural Altmentioning

confidence: 99%

Nicotine and alcohol: the role of midbrain dopaminergic neurons in drug reinforcement

Morel

Montgomery

Han

2018

Eur J of Neuroscience

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Nicotine and alcohol addiction are leading causes of preventable death worldwide and continue to constitute a huge socio‐economic burden. Both nicotine and alcohol perturb the brain's mesocorticolimbic system. Dopamine (DA) neurons projecting from the ventral tegmental area (VTA) to multiple downstream structures, including the nucleus accumbens, prefrontal cortex, and amygdala, are highly involved in the maintenance of healthy brain function. VTA DA neurons play a crucial role in associative learning and reinforcement. Nicotine and alcohol usurp these functions, promoting reinforcement of drug taking behaviors. In this review, we will first describe how nicotine and alcohol individually affect VTA DA neurons by examining how drug exposure alters the heterogeneous VTA microcircuit and network‐wide projections. We will also examine how coadministration or previous exposure to nicotine or alcohol may augment the reinforcing effects of the other. Additionally, this review briefly summarizes the role of VTA DA neurons in nicotine, alcohol, and their synergistic effects in reinforcement and also addresses the remaining questions related to the circuit‐function specificity of the dopaminergic system in mediating nicotine/alcohol reinforcement and comorbidity.

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A concurrent excitation and inhibition of dopaminergic subpopulations in response to nicotine

Cited by 31 publications

References 39 publications

Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors

Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

Nicotine and alcohol: the role of midbrain dopaminergic neurons in drug reinforcement

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