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Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, 300 Medical Plaza, Suite 2200, Los Angeles, CA 90095, USA Positron Emission Tomography Center, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, USA Department of Physics, University of California at Irvine, Irvine, CA, USA Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described.To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo).Randomized, double-blind, before-after controlled trial.Academic brain imaging center.Thirty nicotine-dependent smokers (paid volunteers).Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind).Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos.Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants.Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions.

Our group recently reported that smoking a regular cigarette (1.2-1.4 mg nicotine) resulted in 88% occupancy of brain alpha4beta2* nicotinic acetylcholine receptors (nAChRs). However, this study did not determine whether nicotine inhalation or the many other pharmacological and behavioural factors that occur during smoking resulted in this receptor occupancy. If nicotine is solely responsible for alpha4beta2* nAChR occupancy from smoking, then (as estimated from our previous data) smoking a denicotinized (0.05 mg nicotine) or a low-nicotine (0.6 mg nicotine) cigarette (commonly used for research and clinical purposes) would result in substantial 23% and 78% alpha4beta2* nAChR occupancies, respectively, and a plasma nicotine concentration of 0.87 ng/ml would result in 50% alpha4beta2* nAChR occupancy (EC50). Twenty-four positron emission tomography sessions were performed on tobacco-dependent smokers, using 2-[F-18]fluoro-A-85380 (2-FA), a radiotracer that binds to alpha4beta2* nAChRs. 2-FA displacement was determined from before to 3.1 hours after either: no smoking, smoking a denicotinized cigarette, or smoking a low-nicotine cigarette. Analysis of this PET data revealed that smoking a denicotinized and a low-nicotine cigarette resulted in 26% and 79% alpha4beta2* nAChR occupancies, respectively, across three regions of interest. The EC50 determined from this dataset was 0.75 ng/ml. Given the consistency of findings between our previous study with regular cigarettes and the present study, nicotine inhalation during smoking appears to be solely responsible for alpha4beta2* nAChR occupancy, with other factors (if present at all) having either short-lived or very minor effects. Furthermore, smoking a denicotinized cigarette resulted in substantial nAChR occupancy.

The distance that larvae of the primary screwworm, Cochliomyia americana C. and P., will migrate from the place where they have dropped to the ground and the depth at which they pupate in the soil were studied under field conditions during the fall of 1935 and the spring of 1936 at Valdosta, Ga. These tests were conducted to determine the advisability of further studies on methods of control for larvae and pupae of the screwworm in carcasses of animals or in the soil near infested animals. Tests on methods of controlling larvae and pupae in the soil and carcass have been conducted by Brody & Knipling (1940).