期刊
JOURNAL OF PSYCHOPHARMACOLOGY
卷 29, 期 3, 页码 300-311出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/0269881114562091
关键词
Guanfacine; smoking cessation; stress; fMRI; Stroop; lapse; ad-libitum smoking; craving
资金
- National Institutes of Health [P50DA033945, RL1DA024857, R21DA033597, R01DA035001, UL1DE019586, PL1DA024859, PL1DA024860, UL1RR024139, RL1AA017539, K12DA000167, P20DA027844, R01DA014241]
- Connecticut Department of Mental Health and Addictions Services
Stress and prefrontal cognitive dysfunction have key roles in driving smoking; however, there are no therapeutics for smoking cessation that attenuate the effects of stress on smoking and enhance cognition. Central noradrenergic pathways are involved in stress-induced reinstatement to nicotine and in the prefrontal executive control of adaptive behaviors. We used a novel translational approach employing a validated laboratory analogue of stress-precipitated smoking, functional magnetic resonance imaging (fMRI), and a proof-of-concept treatment period to evaluate whether the noradrenergic alpha 2a agonist guanfacine (3 mg/day) versus placebo (0 mg/day) reduced stress-precipitated smoking in the laboratory, altered cortico-striatal activation during the Stroop cognitive-control task, and reduced smoking following a quit attempt. In nicotine-deprived smokers (n=33), stress versus a neutral condition significantly decreased the latency to smoke, and increased tobacco craving, ad-libitum smoking, and systolic blood pressure in placebo-treated subjects, and these effects were absent or reduced in guanfacine-treated subjects. Following stress, placebo-treated subjects demonstrated decreased cortisol levels whereas guanfacine-treated subjects demonstrated increased levels. Guanfacine, compared with placebo, altered prefrontal activity during a cognitive-control task, and reduced cigarette use but did not increase complete abstinence during treatment. These preliminary laboratory, neuroimaging, and clinical outcome data were consistent and complementary and support further development of guanfacine for smoking cessation.
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