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Véronique DEROCHE-GAMONET




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53 publication(s) since Juillet 1992:


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2019 | Front Behav Neurosci   IF 2.6
Varenicline Targets the Reinforcing-Enhancing Effect of Nicotine on Its Associated Salient Cue During Nicotine Self-administration in the Rat.
Garcia-Rivas V, Fiancette JF, Cannella N, Carbo-Gas M, Renault P, Tostain J, Deroche-Gamonet V

Abstract:
Nicotine is acknowledged as the key addictive compound of tobacco. Varenicline (Champix((R)) or Chantix((R))), mainly acting as a partial agonist at the alpha4beta2 nicotinic receptor, is an approved smoking cessation pharmacotherapy, although with efficacy limited to a portion of smokers. Smokers differ in the motives that drive their drug seeking and Varenicline might be more efficient in some groups more than others. Studies in rodents revealed that nicotine-seeking is strongly supported by complex interactions between nicotine and environmental cues, and notably the ability of nicotine to enhance the reinforcing properties of salient environmental stimuli. It is not yet understood whether the decrease of nicotine-seeking by acute Varenicline in rats results from antagonism of the primary reinforcing effects of nicotine, of the reinforcement-enhancing effect of nicotine on cues, or of a combination of both. Thanks to a protocol that allows assessment of the reinforcement-enhancing effect of nicotine on cues during self-administration in rats, we showed that Varenicline targets both nicotine reinforcing effects and reinforcement-enhancing effect of nicotine on cues. Importantly, individual variations in the latter determined the amplitude of acute Varenicline-induced decrease in seeking. These results suggest that Varenicline might be more beneficial in smokers who are more sensitive to nicotine effects on surrounding stimuli.




05/03/2018 | Mol Psychiatry   IF 12
Depleting adult dentate gyrus neurogenesis increases cocaine-seeking behavior.
Deroche-Gamonet V, Revest JM, Fiancette JF, Balado E, Koehl M, Grosjean N, Abrous DN, Piazza PV

Abstract:
The hippocampus is the main locus for adult dentate gyrus (DG) neurogenesis. A number of studies have shown that aberrant DG neurogenesis correlates with many neuropsychiatric disorders, including drug addiction. Although clear causal relationships have been established between DG neurogenesis and memory dysfunction or mood-related disorders, evidence of the causal role of DG neurogenesis in drug-seeking behaviors has not been established. Here we assessed the role of new DG neurons in cocaine self-administration using an inducible transgenic approach that selectively depletes adult DG neurogenesis. Our results show that transgenic mice with decreased adult DG neurogenesis exhibit increased motivation to self-administer cocaine and a higher seeking response to cocaine-related cues. These results identify adult hippocampal neurogenesis as a key factor in vulnerability to cocaine addiction.




Abstract:
Tobacco use leads to 6 million deaths every year due to severe long-lasting diseases. The main component of tobacco, nicotine, is recognized as one of the most addictive drugs, making smoking cessation difficult, even when 70 percent of smokers wish to do so. Clinical and preclinical studies have demonstrated consistently that nicotine seeking is a complex behavior involving various psychopharmacological mechanisms. Evidence supports that the population of smokers is heterogeneous, particularly as regards the breadth of motives that determine the urge to smoke. Here, we review converging psychological, genetic and neurobiological data from clinical and preclinical studies supporting that the mechanisms controlling nicotine seeking may vary from individual to individual. It appears timely that basic neuroscience integrates this heterogeneity to refine our understanding of the neurobiology of nicotine seeking, as tremendous progress has been made in modeling the various psychopharmacological mechanisms driving nicotine seeking in rodents. For a better understanding of the mechanisms that drive nicotine seeking, we emphasize the need for individual-based research strategies in which nicotine seeking, and eventually treatment efficacy, are determined while taking into account individual variations in the mechanisms of nicotine seeking.




02/2017 | Neuropsychopharmacology   IF 7.2
Individual Variations in the Mechanisms of Nicotine Seeking: A Key for Research on Nicotine Dependence.
Garcia-Rivas V, Cannella N, Deroche-Gamonet V

Abstract:





27/11/2015 | Neuropsychopharmacology   IF 7.2
Differential Control of Cocaine Self-Administration by GABAergic and Glutamatergic CB1 Cannabinoid Receptors.
Martin-Garcia E, Bourgoin L, Cathala A, Kasanetz F, Mondesir M, Gutierrez-Rodriguez A, Reguero L, Fiancette JF, Grandes P, Spampinato U, Maldonado R, Piazza PV, Marsicano G, Deroche-Gamonet V

Abstract:
The type 1 cannabinoid receptor (CB1) modulates numerous neurobehavioral processes and is therefore explored as a target for the treatment of several mental and neurological diseases. However, previous studies have investigated CB1 by targeting it globally, regardless of its two main neuronal localizations on glutamatergic and GABAergic neurons. In the context of cocaine addiction this lack of selectivity is critical since glutamatergic and GABAergic neuronal transmission is involved in different aspects of the disease. To determine whether CB1 exerts different control on cocaine-seeking according to its two main neuronal localizations, we used mutant mice with deleted CB1 in cortical glutamatergic neurons (Glu-CB1) or in forebrain GABAergic neurons (GABA-CB1). In Glu-CB1, gene deletion concerns the dorsal telencephalon, including neocortex, paleocortex, archicortex, hippocampal formation and the cortical portions of the amygdala. In GABA-CB1, it concerns several cortical and non-cortical areas including the dorsal striatum, nucleus accumbens, thalamic and hypothalamic nuclei. We tested complementary components of cocaine self-administration, separating the influence of primary and conditioned effects. Mechanisms underlying each phenotype were explored using in vivo microdialysis and ex vivo electrophysiology. We show that CB1 expression in forebrain GABAergic neurons controls mouse sensitivity to cocaine, while CB1 expression in cortical glutamatergic neurons controls associative learning processes. In accordance, in the nucleus accumbens, GABA-CB1 receptors control cocaine-induced dopamine release and Glu-CB1 receptors control AMPAR/NMDAR ratio; a marker of synaptic plasticity. Our findings demonstrate a critical distinction of the altered balance of Glu-CB1 and GABA-CB1 activity that could participate in the vulnerability to cocaine abuse and addiction. Moreover, these novel insights advance our understanding of CB1 neuropathophysiology.Neuropsychopharmacology accepted article preview online, 27 November 2015. doi:10.1038/npp.2015.351.






17/03/2014 | Neuropsychopharmacology   IF 7.2
Frequency of Cocaine Self-Administration Influences Drug Seeking in the Rat: Optogenetic Evidence for a Role of the Prelimbic Cortex.
Martin-Garcia E, Courtin J, Renault P, Fiancette JF, Wurtz H, Simonnet A, Levet F, Herry C, Deroche-Gamonet V

Abstract:
High-frequency intake and high drug-induced seeking are associated with cocaine addiction in both human and animals. However, their relationships and neurobiological underpinnings remain hypothetical. The medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and nucleus accumbens (NAc) have been shown to have a role in cocaine seeking. However, their involvement in regulating high-frequency intake and high cocaine-induced seeking is unclear. We manipulated frequency of cocaine self-administration and investigated whether it influenced cocaine seeking. The contribution of the aforementioned structures was evaluated using changes in expression of the immediate early gene c-Fos and targeted optogenetic manipulations. Rats that self-administered at High frequency (short inter-infusion intervals allowed by short time-out) showed higher cocaine-induced seeking than low frequency rats (long inter-infusions intervals imposed by long time-out), as measured with cocaine-induced reinstatement. c-Fos was enhanced in High frequency rats in the prelimbic (PL) and infralimbic (IL) areas of the mPFC, the BLA, and the NAc core and shell. Correlational analysis of c-Fos revealed that the PL was a critical node strongly correlated with both the IL and NAc core in High frequency rats. Targeted optogenetic inactivation of the PL decreased cocaine-induced reinstatement, but increased cocaine self-administration, in High frequency rats. In contrast, optogenetic activation of the PL had no effect on Low frequency rats. Thus, high-frequency intake promotes a PL-dependent control of cocaine seeking, with the PL exerting a facilitatory or inhibitory effect, depending on operant contingencies. Individual differences in cocaine-induced PL activation might be a source of vulnerability for poorly controlled cocaine-induced seeking and/or cocaine intake.Neuropsychopharmacology advance online publication, 16 April 2014; doi:10.1038/npp.2014.66.




03/01/2014 | Science   IF 41
Pregnenolone can protect the brain from cannabis intoxication.
Vallee M, Vitiello S, Bellocchio L, Hebert-Chatelain E, Monlezun S, Martin-Garcia E, Kasanetz F, Baillie GL, Panin F, Cathala A, Roullot-Lacarriere V, Fabre S, Hurst DP, Lynch DL, Shore DM, Deroche-Gamonet V, Spampinato U, Revest JM, Maldonado R, Reggio PH, Ross RA, Marsicano G, Piazza PV

Abstract:
Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Delta(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.




Abstract:
Transition to addiction is the shift from controlled to uncontrolled drug use that occurs after prolonged drug intake in a limited number of drug users. A major challenge of addiction research in recent years has been to develop models for studying this pathological transition. Toward this goal, a DSM-IV/5-based multi-symptomatic model of cocaine addiction has been developed in the rat. It is based on an operational translation of the main features of the disease. 1. Addiction is not just taking drug; it is a non-adaptive drug use: The procedure models addiction in relation to its clinical definition. 2. All drug users do not face the same individual risk of developing addiction: The model includes an individual-based approach. 3. Addiction develops after protracted periods of controlled drug use: This procedure allows for the study of the long-term shift from controlled drug use to addiction. We describe this model in detail and show how it can contribute to our understanding of the pathophysiology of cocaine addiction. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.




10/2013 | Psychopharmacology (Berl)   IF 3.4
A multistep general theory of transition to addiction.
Piazza PV, Deroche-Gamonet V

Abstract:
BACKGROUND: Several theories propose alternative explanations for drug addiction. OBJECTIVES: We propose a general theory of transition to addiction that synthesizes knowledge generated in the field of addiction into a unitary explanatory frame. MAJOR PRINCIPLES OF THE THEORY: Transition to addiction results from a sequential three-step interaction between: (1) individual vulnerability; (2) degree/amount of drug exposure. The first step, sporadic recreational drug use is a learning process mediated by overactivation of neurobiological substrates of natural rewards that allows most individuals to perceive drugs as highly rewarding stimuli. The second, intensified, sustained, escalated drug use occurs in some vulnerable individuals who have a hyperactive dopaminergic system and impaired prefrontal cortex function. Sustained and prolonged drug use induces incentive sensitization and an allostatic state that makes drugs strongly wanted and needed. Habit formation can also contribute to stabilizing sustained drug use. The last step, loss of control of drug intake and full addiction, is due to a second vulnerable phenotype. This loss-of-control-prone phenotype is triggered by long-term drug exposure and characterized by long-lasting loss of synaptic plasticity in reward areas in the brain that induce a form of behavioral crystallization resulting in loss of control of drug intake. Because of behavioral crystallization, drugs are now not only wanted and needed but also pathologically mourned when absent. CONCLUSIONS: This general theory demonstrates that drug addiction is a true psychiatric disease caused by a three-step interaction between vulnerable individuals and amount/duration of drug exposure.