Addiction and dopamine: sex differences and insights from studies of smoking

Petersen, Nicole; London, Edythe D.

doi:10.1016/j.cobeha.2018.07.002

Cited by 11 publications

(4 citation statements)

References 137 publications

(125 reference statements)

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“…Additionally, they are more susceptible due to hormonal differences [36]. Several studies providing evidence of gender influence on the genetic-smoking relationship are available [9,11,35]. Interestingly, as association between the assessed SNPs and smoking was only observed for the homozygous variant genotypes, in accordance to other reports for European populations [28,32,37].…”

Section: Discussionsupporting

confidence: 80%

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CHRNA5/CHRNA3 polymorphisms and tobacco smoking risk in a Brazilian population sample

Mota

Mitri

Barata-Silva

et al. 2020

GSC Biol. and Pharm. Sci.

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Tobacco smoking is a major risk factor of several diseases such as lung cancer, stroke, chronic obstructive pulmonary disease and increases the susceptibility to infectious diseases. The understanding of smoking addiction requires phenotyping and genotyping studies. Variations in CHRNA5/CHRNA3 can alter receptor responses to nicotine and thus interfere with smoking behavior and risk. Therefore, this study aimed to investigate the association of CHRNA5 rs16969968 and CHRNA3 rs578776 with smoking behavior in a Brazilian population sample, comprising 449 subjects. Smoking data was obtained from a questionnaire. The polymorphisms were genotyped by Polymerase Chain Reaction (PCR). Associations were verified using logistic and linear regression analyses. We found that women with the variant AA genotype for CHRNA5 rs16969968 were at significantly increased risk of smoking, with an OR of 3.09 (95% CI: 1.09-8.76; p= 0.033). The variant TT genotype of CHRNA3 rs578776 showed protection against smoking and later smoking initiation in the overall population and in women, with an OR of 0.41 (95% CI: 0.19-0.88; p=0.022). In conclusion, CHRNA5 rs16969968 and CHRNA3 rs578776 were associated with increased risk and protective effect against smoking, respectively, in a Brazilian population sample. Gender and recessive homozygosis of the polymorphisms variants resulted in a significant effect regarding the results.

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Section: Discussionsupporting

confidence: 80%

“…The same was noted for the CHRNA5 rs16969968 variant, only associated with increased risk of smoking in women. Some authors have suggested that women tend to evolve from experimentation to addiction more quickly and have greater difficulty in quitting smoking [34,35]. Additionally, they are more susceptible due to hormonal differences [36].…”

Section: Discussionmentioning

confidence: 99%

CHRNA5/CHRNA3 polymorphisms and tobacco smoking risk in a Brazilian population sample

Mota

Mitri

Barata-Silva

et al. 2020

GSC Biol. and Pharm. Sci.

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“…Time 1), and the smoking-by-sex interaction for each MRS metabolite level in the dACC, with age as a covariate. Sex was included as an independent variable based on a priori evidence of sex differences related to smoking [ 37 – 41 ] and of sex differences in metabolites irrespective of smoking [ 42 – 44 ]. The repeated measures testing assessed the reliability of the MRS scans and, in Smoking participants, detected any effects of breaking abstinence still evident 25–55 min after smoking.…”

Section: Discussionmentioning

confidence: 99%

Smoking, tobacco dependence, and neurometabolites in the dorsal anterior cingulate cortex

O’Neill,

Diaz,

Alger

et al. 2023

Mol Psychiatry

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Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warrants further investigation. The goal of this project therefore was to validate and extend evidence of hypoinflammation related to smoking, and to examine the potential contribution of inflammation to clinical features of smoking. Using magnetic resonance spectroscopy, we measured levels of neurometabolites that are putative neuroinflammatory markers. N-acetyl compounds (N-acetylaspartate + N-acetylaspartylglutamate), glutamate, creatine, choline-compounds (phosphocholine + glycerophosphocholine), and myo-inositol, have all been linked to neuroinflammation, but they have not been examined as such with respect to smoking. We tested whether people who smoke cigarettes have brain levels of these metabolites consistent with decreased neuroinflammation, and whether clinical features of smoking are associated with levels of these metabolites. The dorsal anterior cingulate cortex was chosen as the region-of-interest because of previous evidence linking it to smoking and related states. Fifty-four adults who smoked daily maintained overnight smoking abstinence before testing and were compared with 37 nonsmoking participants. Among the smoking participants, we tested for associations of metabolite levels with tobacco dependence, smoking history, craving, and withdrawal. Levels of N-acetyl compounds and glutamate were higher, whereas levels of creatine and choline compounds were lower in the smoking group as compared with the nonsmoking group. In the smoking group, glutamate and creatine levels correlated negatively with tobacco dependence, and creatine correlated negatively with lifetime smoking, but none of the metabolite levels correlated with craving or withdrawal. The findings indicate a link between smoking and a hypoinflammatory state in the brain, specifically in the dorsal anterior cingulate cortex. Smoking may thereby increase vulnerability to infection and brain injury.

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“…While sex differences in the pervasiveness and prognosis of these disorders have long been known to exist, we still lack a complete understanding of why these differences emerge. Many of these disorders are characterized by dysfunction in the dopamine system in reward-related brain regions [3,4], and as such, there has been considerable interest in outlining the sex differences in dopaminergic anatomy, regulation, and function in preclinical models. Many sex differences exist independent of ovarian cycle fluctuations and reflect differences in basal dopamine system organization/neuroanatomy [5][6][7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in dopamine release regulation in the striatum

Zachry

Nolan

Brady

et al. 2020

Neuropsychopharmacol.

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The mesolimbic dopamine system-which originates in the ventral tegmental area and projects to the striatum-has been shown to be involved in the expression of sex-specific behavior and is thought to be a critical mediator of many psychiatric diseases. While substantial work has focused on sex differences in the anatomy of dopamine neurons and relative dopamine levels between males and females, an important characteristic of dopamine release from axon terminals in the striatum is that it is rapidly modulated by local regulatory mechanisms independent of somatic activity. These processes can occur via homosynaptic mechanisms-such as presynaptic dopamine autoreceptors and dopamine transporters-as well as heterosynaptic mechanisms, such as retrograde signaling from postsynaptic cholinergic and GABAergic systems, among others. These regulators serve as potential targets for the expression of sex differences in dopamine regulation in both ovarian hormone-dependent and independent fashions. This review describes how sex differences in microcircuit regulatory mechanisms can alter dopamine dynamics between males and females. We then describe what is known about the hormonal mechanisms controlling/regulating these processes. Finally, we highlight the missing gaps in our knowledge of these systems in females. Together, a more comprehensive and mechanistic understanding of how sex differences in dopamine function manifest will be particularly important in developing evidence-based therapeutics that target this system and show efficacy in both sexes.

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Addiction and dopamine: sex differences and insights from studies of smoking

Cited by 11 publications

References 137 publications

CHRNA5/CHRNA3 polymorphisms and tobacco smoking risk in a Brazilian population sample

CHRNA5/CHRNA3 polymorphisms and tobacco smoking risk in a Brazilian population sample

Smoking, tobacco dependence, and neurometabolites in the dorsal anterior cingulate cortex

Sex differences in dopamine release regulation in the striatum

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