Why Some Smokers Become Addicted With Their First Cigarette
New research from The University of Western Ontario reveals how the brain processes the ‘rewarding’ and addictive properties of nicotine, providing a better understanding of why some people seemingly become hooked with their first smoke.
The research, led by Steven Laviolette of the Department of Anatomy and Cell Biology at the Schulich School of Medicine & Dentistry could lead to new therapies to prevent nicotine dependence and to treat nicotine withdrawal when smokers try to quit.
“Nicotine interacts with a variety of neurochemical pathways within the brain to produce its rewarding and addictive effects,” explains Laviolette. “However, during the early phase of tobacco exposure, many individuals find nicotine highly unpleasant and aversive, whereas others may become rapidly dependent on nicotine and find it highly rewarding. We wanted to explore that difference.”
The researchers found one brain pathway in particular uses the neurotransmitter ‘dopamine’ to transmit signals related to nicotine’s rewarding properties. This pathway is called the ‘mesolimbic’ dopamine system and is involved in the addictive properties of many drugs of abuse, including cocaine, alcohol and nicotine.
“While much progress has been made in understanding how the brain processes the rewarding effects of nicotine after the dependence is established, very little is known about how the mesolimbic dopamine system may control the initial vulnerability to nicotine; that is, why do some individuals become quickly addicted to nicotine while others do not, and in some cases, even find nicotine to be highly aversive.”
The scientists identified which specific dopamine receptor subtype controlled the brain’s initial sensitivity to nicotine’s rewarding and addictive properties and were able to manipulate these receptors to control whether the nicotine is processed as rewarding or aversive.
“Importantly, our findings may explain an individual’s vulnerability to nicotine addiction, and may point to new pharmacological treatments for the prevention of it, and the treatment of nicotine withdrawal,” says Laviolette. The research was funded by the Canadian Institutes of Health Research and the Canadian Psychiatric Research Foundation.
J. Neurosci. 2008 28: 8025-8033; doi:10.1523/JNEUROSCI.1371-08.2008
Dopamine Signaling through D1-Like versus D2-Like Receptors in the Nucleus Accumbens Core versus Shell Differentially Modulates Nicotine Reward Sensitivity
Steven R. Laviolette, Nicole M. Lauzon, Stephanie F. Bishop, Ninglei Sun, and Huibing Tan
Considerable evidence implicates the mesolimbic dopamine (DA) system in the processing of nicotine’s reinforcing properties, specifically the ventral tegmental area (VTA) and the terminal fields of VTA DAergic projections to the “core” (NAcore) and “shell” (NAshell) subdivisions of the nucleus accumbens (NAc). However, the specific roles of DA D1-like and D2-like receptor subtypes in nicotine reward processing within these NAc subregions have not been elucidated. We report that microinfusions of DA D1-like or D2-like receptor-specific antagonists into NAcore or NAshell double dissociate the rewarding and aversive properties of systemic or intra-VTA nicotine, and differentially regulate sensitivity to the rewarding properties as well as the motivational valence of either intra-VTA or systemic nicotine administration. Using a place conditioning procedure, NAshell infusions of a D2-like receptor antagonist switched the motivational valence of intra-VTA nicotine from aversive to rewarding and potentiated nicotine reward sensitivity to sub-reward threshold intra-VTA nicotine doses. In contrast, NAcore infusions of a D1-like receptor antagonist switched intra-VTA nicotine aversion to reward, and potentiated reward sensitivity to sub-reward threshold nicotine doses. Thus, D1-like versus D2-like receptors in NAcore versus NAshell subdivisions play functionally dissociable roles in modulating systemic or intra-VTA nicotine motivational processing.