Bordeaux Neurocampus

Webinar - Sébastien Carnicella
2022-01-28 11:30 - 12:30 (Europe/Paris)
Sébastien Carnicella
Grenoble Institut Neurosciences
Webpage https://neurosciences.univ-grenoble-alpes.fr/
Invited by Clémentine Bosch-Bouju (Nutrineuro)

On Zoom

Title
Implication of hypodopaminergic state of the nigrostriatal pathway in compulsive alcohol-related behaviors

Abstract
Neurobiological mechanisms underlying compulsive alcohol use, a cardinal problem of addiction, remain elusive. Dopamine (DA), key modulator of motivational processes, is suspected to play an important role in this pathology, but its exact implication remains to be determined. Here, we found that rats expressing a compulsive alcohol-related behavior presented a decrease of DA levels restricted to the dorsolateral-striatum, a main output structure of the DA nigrostriatal pathway. Using chemogenetic, we induced a selective hypodopaminergia of nigrostriatal pathway. This alteration led to motivational impairments reminiscent of alcohol withdrawal and to the emergence of compulsive-alcohol related behavior in rats that do not initially express this phenotype. These results identify and demonstrate a major implication of tonic hypodopaminergic state in alcohol addiction and provide new insights to understand neurobiological mechanism underlying compulsive alcohol use.
Selected publications
Goutaudier R, Coizet V, Carcenac C, Carnicella S. Compound 21, a two-edged sword with both DREADD-selective and off-target outcomes in rats. PLoS One, 2020 15(9): e0238156
Goutaudier R, Coizet V, Carcenac C, Carnicella S. DREADDs: The Power of the Lock, the Weakness of the Key. Favoring the Pursuit of Specific Conditions Rather than Specific Ligands. eNeuro, 2019 6(5): ENEURO.0171-19.2019
Drui G*, Carnicella S*, Carcenac C, Favier M, Bertrand A, Boulet S, Savasta M. Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson’s disease. Mol Psychiatry, 2014 19(3): 358-67
Barak S*, Carnicella S*, Yowell QV, Ron D. Glial cell line-derived neurotrophic factor reverses alcohol-induced allostasis of the mesolimbic dopaminergic system: implications for alcohol reward and seeking. J Neurosci, 2011 31(27):9885-94
Carnicella S, Kharazia V, Jeanblanc J, Janak PH, Ron D. GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse. Proc Natl Acad Sci U S A, 2008 105(23):8114-9
