Abstract
Recent evidence has implicated the endocannabinoid (eCB) system in nicotine addiction. The eCB system also has an important role in reward mechanisms, and nicotine addiction has been associated with aberrant reward processing. Motivated by this evidence, we tested the hypothesis that eCB modulation of reward processing is altered in subjects with a nicotine addiction (NAD). For this purpose, we compared reward-related activity in NAD with healthy controls (HC) in a pharmacological magnetic resonance imaging (MRI) study using Δ9-tetrahydrocannabinol (THC) administration to challenge the eCB system. Eleven HC and 10 NAD participated in a 3-T functional MRI (fMRI) study with a double-blind, cross-over, placebo-controlled design, using a Monetary Incentive Delay (MID) paradigm with three reward levels. Reward activity in the nucleus accumbens (NAcc) and caudate putamen during anticipation and feedback of reward was compared after THC and placebo. fMRI results indicated a significant reduction of reward anticipation activity in the NAcc in NAD after THC administration, which was not present in HC. This is indicated by a significant group by drug by reward interaction. Our data show that THC significantly reduces the NAcc response to monetary reward anticipation in NAD. These results suggest that nicotine addiction is associated with altered eCB modulation of reward processing in the NAcc. This study adds important human data to existing evidence implicating the eCB system in nicotine addiction.
Highlights
Recent estimates of the World Health Organization have shown that there are about 1.25 billion smokers worldwide and that five million deaths occur each year as a direct result of tobacco use.[1]
For the nucleus accumbens (NAcc), we found that reward increased brain activity in NAcc (F(2,9) 1⁄4 4.91; P 1⁄4 0.04), while in nicotine addiction (NAD) there was no significant increase of brain activity with increasing reward (F(2,8) 1⁄4 1.36; P 1⁄4 0.31)
We found no difference in reward-related activity in NAcc between healthy controls (HC) and NAD (F(2,18) 1⁄4 0.35; P 1⁄4 0.71), while after THC we found a significantly lower reward response in NAcc in NAD compared with HC (F(2,18) 1⁄4 7.64; Pp0.001)
Summary
Recent estimates of the World Health Organization have shown that there are about 1.25 billion smokers worldwide and that five million deaths occur each year as a direct result of tobacco use.[1]. Animal studies have shown that blocking the eCB receptor CB1 with the antagonist rimonabant reduces self-administration of nicotine[4,8] and relapse to nicotine seeking (as well as other drugs, such as cocaine and ethanol).[9] Nicotine withdrawal has been shown to be accompanied by fluctuations in the levels of the eCB anandamide (AEA) in several brain structures in rats.[10] In humans, clinical trials have indicated that rimonabant can facilitate smoking cessation.[2,11] The eCB system has been widely implicated in the reward properties of non-drugs,[12,13] which has recently been supported by human neuroimaging studies.[14,15,16,17] Preclinical studies have, for instance, shown that CB1 receptor agonists can increase food intake,[18,19] whereas the CB1 antagonist rimonabant has been demonstrated to reduce obesity[11] and reduce striatal brain activity during reward processing.[17] In addition, there is evidence of deficient reward processing in nicotine addiction.[20,21,22,23]
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