Accumulating evidence suggests that the antecedents, consequences, and mechanisms of drug abuse and dependence are not identical in males and females and that gender may be an important variable in treatment and prevention. Although there has been a decline in smoking prevalence in developed countries, females are less successful in quitting. Tobacco use is accepted to be a form of addiction, which manifests sex differences. There is also evidence for sex differences in the central effects of nicotine in laboratory animals. Although social factors impact smoking substantially in humans, findings from nonhuman subjects in controlled experiments provide support that sex differences in nicotine/tobacco addiction have a biological basis. Differences in the pharmacokinetic properties of nicotine or the effect of gonadal hormones may underlie some but not all sex differences observed. Laboratory-based information is very important in developing treatment strategies. Literature findings suggest that including sex as a factor in nicotine/tobacco-related studies will improve our success rates in individually tailored smoking cessation programs.

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Smoking is the major cause of preventable deaths worldwide, and although there is a decline in overall smoking prevalence in developed countries, the decline in women is less pronounced than in men. Women become dependent faster and experience greater difficulties in quitting. Similar trends have been observed in animal models of nicotine/tobacco addiction. Individual differences in vulnerability to drug abuse are also observed in nicotine/ tobacco addiction and point to the importance of sex differences. This Review, summarizes findings from three experimental approaches used to depict nicotine preference in animal models, intravenous and oral nicotine selfadministration and nicotine-induced conditioned place preference. Nicotine preference is considered to be reflected in the animal's motivation to administer the drug (intravenously or orally) or to prefer an environment paired with the presence of the drug (conditioned place preference). These approaches all point to the importance of sex and age of the subjects; the preference of females and adolescents appear to be more pronounced than that of males and adults, respectively. A closer look at these factors will help us understand the mechanisms that underlie nicotine addiction and develop strategies to cope. Ignoring sex differences and reaching conclusions based only on studies using male subjects has resulted in erroneous generalizations in the past. Sex differences in nicotine preference have been clearly documented, and awareness on this aspect of nicotine dependence will significantly impact our success in translational research. V C 2016 Wiley Periodicals, Inc.

Cocaine and amphetamine-regulated transcript (CART) peptides are suggested to play a role in several physiological processes including feeding, reward, neuroendocrine modulation, and the stress response. Although some studies implicate the modulation of CART peptide expression by glucocorticoids, direct evidence relating CART to the stress response is limited. The present study was undertaken to evaluate the possible involvement of CART peptides during acute stress in male and female rats. Forced swim was used as the stress procedure. Following stress, serum adrenocorticotropic hormone (ACTH), and corticosterone (CORT) levels were determined, and CART immunocytochemistry was performed in the paraventricular (PVN) and arcuate (ARC) nuclei of the hypothalamus. Our results depict the following changes: (1) Serum ACTH and CORT levels were increased by stress and CORT levels were higher in female rats than males. (2) Stress modulated the number of CART expressing neurons. The degree and direction of this modulation varied according to the hypothalamic region and the sex of the subject. Forced swim stress increased CART peptide expression significantly in the PVN of female rats. In males, although there was a tendency for an increase in CART-immunoreactive cells by forced swim stress, the difference was not statistically significant. In the ARC nucleus, forced swim stress did not affect CART peptide expression in either sex. Our results suggest differential and sexually dimorphic modulation of CART expression in the PVN and ARC by forced swim stress.

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