Aller au contenuAller au menuAller à la recherche

Séminaire - Paul KennyIdentification of a novel intralaminar thalamus circuit that controls compulsive nicotine intake.

Abstract :

Habitual tobacco smokers allocate disproportionate amounts of time and effort to obtain nicotine at the expense of natural rewards, even when serious health consequences can ensue. How nicotine comes to dominate behavior in tobacco addicts is poorly understood. Hypocretin (orexin) is a hypothalamic neuropeptide thought to regulate nicotine intake by controlling its rewarding effects.

Contrary to this view, I will present new data demonstrating that hypocretin plays no role whatsoever in nicotine reward. Instead hypocretin is shown to control the allocation of behavioral resources, such as amounts of time or effort, dedicated to obtaining infusions of the drug. Surprisingly, hypocretin controls the “value” of nicotine infusions not through midbrain dopamine systems but instead by stimulating a previously uncharacterized population of thalamic GABAergic neurons located in close proximity to the lateral habenula.

These hypocretin-responsive neurons are in turn shown to inhibit surrounding intralaminar thalamic neurons and thereby regulate nicotine value. I will also show that chemicogenetic stimulation of hypocretin inputs to these novel thalamic GABAergic neurons, or inhibition of surrounding intralaminar neurons, precipitates addiction-like increases in the value of nicotine, reflected in persistent responding for the drug even when its delivery is paired with punishing footshocks.

I will speculate that dysfunction in this thalamic circuit may explain the irrationality of tobacco addiction in which smokers persist in the habit despite a desire to quit and awareness of the potentially fatal consequences.

Selected publications

Fowler CD, Lu Q, Johnson PM Marks MJ & Kenny PJ (2011) Habenular α5* nicotinic receptor signaling controls nicotine intake. Nature 471(7340):597-601.

Kenny PJ (2011) Reward mechanisms in obesity: New insights and future directions. Neuron 69:664-79.

Im H-I, Hollander JA, Bali P & Kenny PJ (2010) MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nature Neuroscience 13(9):1120-7.

Schaefer A, Im H-I, Venø MT, Fowler CD, Min A, Intrator A, Kjems J, Kenny PJ, O’Carroll D & Greengard P (2010) Argonaute 2 in dopamine 2 receptor expressing neurons regulates cocaine addiction. Journal of Experimental Medicine 207(9):1843-51.

Hollander JA, Im H-I, Amelio A, Kocerha J, Bali P, Lu Q, Willoughby D, Wahlestedt C, Conkright M & Kenny PJ (2010) Striatal microRNA controls cocaine intake through regulation of CREB signaling. Nature 466, 197–202.

Johnson P & Kenny PJ (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature Neuroscience 13(5):635-41.

Scientific focus :

the Kenny Laboratory   link....


Our research is focused on understanding the molecular neurobiology of drug addiction and obesity, with an emphasis on developing novel therapeutics for these disorders.  We take a multidisciplinary approach that includes mouse behavioral genetics, viral-mediated gene transfer, protein and RNA biology, and we combine these techniques with complex behavioral procedures to better understand the mechanics of addiction and obesity. Current projects include understanding the role of noncoding RNAs and other epigenetic machineries in addiction, identifying the nicotinic receptor subunits that regulate tobacco dependence, investigating the role of brain reward pathways in obesity, and developing small molecule therapeutics for addiction. 

Martine Cador et Véronique Deroche (martine.cador @ u-bordeaux2.fr)

Focus


Paul J. Kenny, Ph.D.
Associate Professor
Laboratory for Behavioral and Molecular Neuroscience
The Scripps Research Institute - Scripps Florida
Departments of Molecular Therapeutics and Neuroscience,
Jupiter, FL, 33458, USA

 

What are Scripps Florida's major areas of scientific interest?

Scripps Florida is an academic research facility with investigators in six of the institute's 15 departments: Cancer Biology, Chemistry, Infectology, Metabolism and Aging, Molecular Therapeutics and Neuroscience, as well as the unique Translational Research Institute, which includes the Advanced Technologies and Drug Discovery divisions.
While the focus of basic scientific research is to understand the mechanisms that lead to disease and its potential treatment, the Translational Research Institute seeks to identify new biochemical targets for drug development, and to optimize and further develop these drug candidate lead compounds...read more