Perkins KA, Donny E, Caggiula AR. Sex differences in nicotine effects and self-administration: review of human and animal evidence. Nicotine Tob Res 1: 301-315

Department of Psychiatry, University of Pittsburgh Medical Center, Pennsylvania, USA.
Nicotine & Tobacco Research (Impact Factor: 3.3). 01/2000; 1(4):301-15. DOI: 10.1080/14622299050011431
Source: PubMed


Although both the human and animal literatures are notable for the general lack of attention paid to possible sex differences in drug self-administration behavior, evidence is accumulating to suggest that males and females may differ in factors that maintain tobacco smoking or nicotine self-administration. Self-administration of nicotine per se may be less robust in women, and women are less sensitive than men to some effects of nicotine that may be reinforcing. Compared to men, smoking behavior of women may be influenced more by non-nicotine stimuli associated with smoking, suggesting greater conditioned reinforcement of smoking in women. Moreover, nicotine replacement, the current standard treatment for smoking cessation, is sometimes less effective in women, further suggesting the need for greater consideration of non-nicotine factors that may maintain women's smoking. Very recent research on rats also indicates sex differences in nicotine self-administration. However, these differences are complex and suggest that nicotine-seeking behavior is composed of several components, including hedonic, incentive-motivational, and conditioning effects; males and females may differ in one or more of these components. Menstrual or estrous cycle phase effects on the maintenance of nicotine self-administration are not particularly apparent in humans or animals, although cycle phase may influence other stages of dependence (e.g., withdrawal symptoms during cessation). Future research should evaluate further the consistency of results across human and non-human species, identify the conditions and procedures under which sex differences are observed, and elucidate the specific components of reinforcement that may differ between males and females. Studies also should examine the possible generalizability of these sex differences to other drugs of abuse. Identification of specific factors responsible for these sex differences may lead to improved interventions for smoking cessation and other substance abuse in women.

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Available from: Eric C Donny, Jul 25, 2014
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    • "This finding is consistent with those of other recent studies on alcohol cue-reactivity (e.g., Petit et al., 2013). Yet, despite evidence indicating that men are more responsive to NRT (Perkins et al., 1999), alcohol cue-reactivity was not enhanced for men in the nicotine compared with the placebo condition. A closer examination of drinking patterns revealed that men in our sample reported drinking a significantly greater number of drinks per occasion and more heavy episodic drinking than women. "
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    ABSTRACT: Evidence from alcohol self-administration studies suggests that nicotine replacement therapy may influence subjective and behavioral responses to alcohol. However, its effect on alcohol cue-reactivity is unknown. The present study examined the impact of acutely administered nicotine on subjective responses to alcohol-focused pictorial stimuli. In a mixed within/between-subjects design, nondependent smokers (n = 51) and dependent smokers (n = 45) who socially drink were assigned to either a nicotine (4 mg) or placebo lozenge condition following overnight tobacco abstinence. Following lozenge absorption, participants viewed neutral images followed by alcohol-focused pictures. Craving measures for alcohol and tobacco were completed at baseline, following lozenge absorption, following neutral cues, and following alcohol cues. The presentation of alcohol cues increased alcohol-related craving relative to neutral cues, especially among men, but the administration of nicotine did not influence the magnitude of these effects. Nicotine lozenges were found to decrease intentions to smoke and withdrawal-related craving in dependent but not in nondependent smokers. Finally, the presentation of alcohol cues was found to increase intentions to smoke relative to neutral cues across participants regardless of lozenge condition. Findings suggest that although the presentation of alcohol cues can increase alcohol- and tobacco-related cravings in smokers, such effects do not appear to be affected by acute nicotine administration. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Full-text · Article · Feb 2015 · Experimental and Clinical Psychopharmacology
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    • "These differences are important to consider in developing better treatments for smoking cessation as well as developing forms of nicotine therapy in treatment of neurodegenerative and neurologic disorders. In fact, studies have shown that women find it more difficult to quit smoking than men, and also are less likely to benefit from the use of nicotine replacement therapy in smoking cessation programmes (Perkins et al. [33] [34]). Our results support this sexually dimorphic response of nicotine in respect to modulation of body weight, food consumption and nitric oxide formation. "
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    ABSTRACT: Nicotine is readily consumed through cigarettes; however it is also easily consumed through the various forms of non-prescription nicotine replacement therapy. It has been shown to possess potential therapeutic value for the management of neurologic and neurodegenerative diseases in the last decade. Hence, this study examined the effects of chronic subcutaneous nicotine administration on food intake and body weight as well as on nitric oxide concentrations and total antioxidant capacity in female and male rats. Nicotine was administered to rats via subcutaneous injections at doses of 0.25, 2 and 4 mg/kg body weight for 28 days. Control groups received normal saline; the vehicle for nicotine. Food intake by each group was monitored daily and body weight of the animals was measured twice weekly. At the end of drug administration, blood was obtained from each animal via cardiac puncture for biochemical determination of serum total antioxidant capacity (TAC) and nitric (NO) concentrations using standard assay kits. Results showed significant loss (p < 0.05) of body weight in all nicotine treated female rats. In contrast, male rats showed weight gain, though this was significantly lower (p < 0.001) in nicotine treated groups compared to control. Nicotine significantly reduced (p < 0.001) food consumed in both female and male rats; however dose related changes were observed in only male rats. No significant difference was observed in TAC following nicotine treatments for both female and male rats. Furthermore, only males exhibited changes in NO concentrations following nicotine treatment, as it significantly increased (p < 0.01) NO concentrations in all male treated groups. In conclusion, this study has shown that modulation of body weight, food consumption and nitric oxide formation by nicotine is sexually dimorphic. Also, the study suggests that nicotine modulation of food intake and body weight and its modulation of NO may be independent of each other.
    Full-text · Article · Sep 2014 · Pathophysiology
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    • "Other evidence indicates that there may be sex differences in reactivity to smoking cues. Indeed, exposure to smoking cues may have a more pronounced impact on motivation to smoke and smoking behavior in female smokers relative to male smokers (Field and Duka, 2004; Perkins Donny and Caggiula 1999). Cue reactivity research, in which various aspects of tobacco-related craving and withdrawal are assessed before and after exposure to smoking and neutral cues, has demonstrated that women show a greater increase in craving following smoking cue exposure relative to men (Field and Duka, 2004). "
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    ABSTRACT: Reduced craving associated with nicotine replacement therapy use is frequently attributed to the effects of nicotine pharmacology, however non-pharmacological factors may also play a role. This study examined the impact of nicotine pharmacology and non-pharmacological components of an acute nicotine lozenge (4 mg) on cigarette craving, mood and heart rate in 70 daily smokers (36 male). Smoking-related stimuli were used to assess cue-induced craving. Participants were randomly assigned to one of four conditions in a balanced placebo design where half the participants were provided deceptive information regarding the nicotine content of a lozenge. Subjective ratings of craving and mood were collected and heart rate was assessed before and after neutral and smoking cues. Nicotine expectancy reduced withdrawal-related craving (p=0.006) regardless of actual nicotine administration while combined nicotine expectancy and administration reduced intentions to smoke (p=0.046) relative to each of the other conditions. Exposure to smoking-related stimuli increased cigarette craving (p≤0.001) and negative affect (p≤0.001) regardless of expectancy or pharmacology. Following the smoking cue, women reported a greater increase in withdrawal-related craving than men (p=0.027). Findings suggest that both pharmacological and non-pharmacological components of nicotine lozenge administration contribute to its acute effects on craving, yet neither appears effective in preventing craving triggered by exposure to environmental smoking stimuli.
    Full-text · Article · Jan 2014 · Journal of Psychopharmacology
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