Differential amygdala responses to varenicline and nicotine in acutely-abstinent smokers: Implications for individualized smoking cessation treatment?

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NIDA	PHARM/PHYS-5

* FARE Award Winner

Authors

• M Sutherland
• A Carroll
• BJ Salmeron
• T Ross
• E Stein

Abstract

Varenicline is thought to reduce smoking behaviors by ameliorating abstinence-induced withdrawal while also dampening nicotine-induced effects. The amygdala has been linked with negative affective states accompanying acute withdrawal. Does varenicline reduce amygdala responses in abstinent (>12 hrs) smokers? fMRI was used to assess participants (N=24) after undergoing ~14 days of varenicline- and placebo-pill administration (PILL factor) with nicotine- and placebo-patch (PATCH factor) assessments after each period. A perceptual matching task probed amygdala reactivity in response to novel facial expressions. Smokers were parsed into two groups (GROUP factor) based on varenicline’s impact on reaction time (RT): 1) “responders”, who showed a varenicline-induced RT reduction (-143 ± 24ms); and 2) “non-responders”, in whom varenicline had no effect (39 ± 24ms). Assessing the impact of study drugs on amygdala reactivity in a three-way mixed ANOVA revealed differential effects in these subgroups (PILL x PATCH x GROUP: F[1,21] = 4.4, p = 0.047). In the responder group, both varenicline and nicotine reduced reactivity by 40% and 74%, respectively. However, in the non-responder group, varenicline had no effect, and nicotine actually increased reactivity by 40%. These data indicate subgroups of smokers respond differentially to varenicline and nicotine, an observation that may impact individualized-treatment matching strategies.

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