Sex‐specific differences in GABA_A‐benzodiazepine receptor availability: relationship with sensitivity to pain and tobacco smoking craving

Abstract

Sex-differences exist in tobacco smoking behaviors. Nicotine, the primary addictive ingredient in tobacco smoke indirectly affects γ-amino butyric acid (GABA) function. Previous studies reported sex by smoking interactions in brain GABA levels. The goal of the present study was to evaluate if there is a sex by smoking interaction at the GABAA-benzodiazepine receptors (GABAA-BZRs), as well as relationships between GABAA-BZR availability and behavioral variables before and after 1wk of smoking cessation. Twenty six women (8 nonsmokers, age 36.0 ± 13.4y; 19 smokers, age 34.6 ± 8.9y) and twenty five men (8 nonsmokers, age 37.9 ± 13.8y; 17 smokers, 34.1 ± 12.4y) were imaged using [123I]iomazenil and single photon emission computed tomography (SPECT). Smokers were imaged at baseline 7h after the last cigarette. A significantly great number of men were able to abstain from smoking for 1 week (p=0.003). There were no significant differences in nicotine dependence and cigarette craving, mood or pain sensitivity between male and female smokers. There was a significant effect of sex across all brain regions (frontal, parietal, anterior cingulate, temporal and occipital cortices, and cerebellum; p<0.05), with all women (smokers and nonsmokers combined) having a higher GABAA-BZR availability than all men. There was a negative correlation between GABAA-BZR availability and craving (p≤;0.02) and pain sensitivity (p=0.04) in female but not male smokers. This study provides further evidence of a sex-specific regulation of GABAA-BZR availability in humans and demonstrates the potential for GABAA-BZRs to mediate tobacco smoking craving and pain symptoms differentially in female and male smokers.

Investigating Sex-Specific Characteristics of Nicotine Addiction Using Metabolic and Structural Magnetic Resonance Imaging

“…However, as their study was performed on in vitro plasma samples, direct comparisons cannot be drawn with respect to the observations of the present study. On a similar note, Esterlis et al [47] also demonstrated higher GABA A -benzodiazepine availability in women as compared to men, which is again not comparable to the present study that investigated in vivo GABA concentrations in the frontal lobe. Our findings, however, are in line with the findings of the study by Epperson et al [24], who also showed that female smokers have lower GABA levels as compared to male smokers in occipital cortex.…”

“…Some studies have reported sex-specific alterations in GABA neurotransmission [6,47]. Specifically, Mandal et al [6] showed higher plasma GABA levels in females as compared to males.…”

The Relationship between Smoking Status and Suicidal Behavior in Korean Adults: The 4th Korea National Health and Nutrition Examination Survey (2007-2009)

“…Some studies that analyzed interactions between smoking and brain gamma-aminobutyric acid levels30) support the idea that smoking-related behavior depends not only on social effects but also on biological effects such as gender. However, there have been few studies of the biological relationship between smoking and suicidal behavior by gender; further studies are needed.…”

How Imaging Glutamate, γ‐Aminobutyric Acid, and Dopamine Can Inform the Clinical Treatment of Alcohol Dependence and Withdrawal

“…In addition, neurosteroid levels, implicated in modulating the GABA system during chronic alcohol exposure, fluctuated significantly more in response to chronic alcohol exposure in male than female rodents (Janis et al 1998), which may explain more frequent and severe withdrawal symptoms observed in males (Devaud et al 2006). There is further evidence of higher GABA A receptor availability in healthy women than men (Esterlis et al 2013), suggesting sex differences may play a role in alcohol’s effects on the GABA system. Yet, only one neuroimaging study presented here directly investigated sex differences in alcohol dependence (Lingford-Hughes et al 2000), showing a trend of regional differences in reduced GABA A receptor availability during extended alcohol withdrawal between men and women.…”