Cerebral Monoamine Oxidase A Inhibition in Tobacco Smokers Confirmed With PET and [11C]Befloxatone

Abstract

The inhibition of cerebral monoamine oxidases (MAOs) by cigarette smoke components could participate to the tobacco addiction. However, the actual extent of this inhibition in vivo in smokers is still poorly known. We investigated cerebral MAO-A availability in 7 tobacco-dependent subjects and 6 healthy nonsmokers, using positron emission tomography (PET) and the MAO-A selective radioligand [C]befloxatone. In comparison to nonsmokers, smokers showed a significant overall reduction of [C]befloxatone binding potential (BP) in cortical areas (average reduction, -60%) and a similar trend in caudate and thalamus (-40%). Our findings confirm a widespread inhibition of cerebral MAO-A in smokers. This mechanism may contribute to tobacco addiction and for a possible mood-modulating effect of tobacco.

The Reduction of R1, a Novel Repressor Protein for Monoamine Oxidase A, in Major Depressive Disorder

“…Similarly, R1 and MAO A levels did not correlate with smoking status (possibly due to mild nicotine exposure (Beck et al, 1981), which is consistent with a previous report in regards to the effect of long-term cigarette smoking on the human locus coeruleus (Klimek et al, 2001)). Other studies by Fowler et al (1996) and Leroy et al (2009) show that MAO A levels are decreased in the brains of individuals with chronic, excessive nicotine exposure; however, in the current study, the magnitude of cigarette smoking in most of the subjects was considered to be mild (one pack or less per day; data not shown) in comparison to the Fowler and Leroy study. For the relation of R1 or MAO A with suicide, the statistical analysis showed no differences in the protein expression of R1 or MAO A between suicide and non-suicide groups (Supplementary Table 2).…”

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [11C]befloxatone and the Multi-Injection Approach

“…administration, its selective and reversible binding to MAO-A sites was also confirmed in vivo. Befloxatone appeared safe for its therapeutic use in humans (Rosenzweig et al, 1998) and therefore suitable for clinical PET (Leroy et al, 2009).…”

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

“…Monoamine oxidase is partially inhibited (~30%-40%) in brains of cigarette smokers (Berlin & Anthenelli, 2001;Fowler, Volkow, Wang, Pappas, Logan, MacGregor, et al, 1996;Fowler et al, 1998;Fowler, Volkow, Wang, Pappas, Logan, Shea, et al, 1996;Leroy et al, 2009;Volkow, Fowler, Ding, Wang, & Gatley, 1999) and this decreased MAO activity may be relevant to the addictive properties of cigarettes. Although it is currently unknown what cigarette smoke constituents result in this MAO inhibition, describing the impact of MAO inhibition is an important step for understanding the addictive potential of cigarettes.…”