[I-123]Iomazenil SPECT imaging of GABA-A-benzodiazepine receptor in smokers and nonsmokers

Abstract

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Objectives: Many smokers experience subsyndromal anxiety symptoms while smoking and during acute abstinence, which appear to resolve with extended abstinence. The GABA-A-benzodiazepine receptor (GABA-A-BZR) is the initial site of action of anti-anxiety drugs in brain. Chronic nicotine treatment in rodents induces an upregulation in GABA-A-BZRs. We have hypothesized cortical GABA-A-BZR is higher in smokers compared to nonsmokers and that GABA-A-BZR availability correlates with the degree of subsyndromal anxiety. Methods: We imaged cortical GABA-A-BZR using [I-123]Iomazenil and single photon emission computed tomography (SPECT). To date, fifteen control smokers (8 men; 7 women mean age = 41.3±8.3) and fifteen healthy nonsmokers (8 men; 7 women; mean age = 34.5±12.4) have been imaged. [I-123]Iomazenil (6mCi) was injected intravenously using a bolus to constant infusion ratio of 7.5 and three 12 min scans were acquired starting at hour 6. Tobacco smokers smoked on average 17.1±3.7 cigarettes per day. Women were imaged during the follicular phase of their menstrual cycle. Smokers were imaged 7 h after last cigarette; plasma and urine cotinine levels at the time of the scan were >100ng/mL. Results: Preliminary region of interest analyses of n=14 smokers (7 men; 7 women) and n=14 age and sex-matched nonsmokers show a trend toward higher [I-123]Iomazenil uptake in smokers in the frontal (18.3%), parietal (18.2%), anterior cingulate (15.4%), and occipital (14.3%) cortices; whereas there was no difference (0%) in the thalamus and cerebellum. Interestingly, there was also a tendency toward a negative correlation between [I-123]Iomazenil uptake in the anterior cingulate (r=-.63, p=.04), temporal (r=-.56, p=.09), and cerebellar (r=-.59, p=.07) cortices and state anxiety (measured by Speilberger’s STAI) in smokers, suggesting that smokers with lower GABA-A-BZR availability are more vulnerable to subsyndromal anxiety symptoms. Conclusions: While preliminary, these findings suggest that the regulatory effects of tobacco smoke (or the lack of) on GABA-A-BZR availability may determine vulnerability to subsyndromal anxiety symptoms in tobacco smokers.

Research Support (if any): TTURC P5015632 and NIDA T32 Award