Sex differences in the influence of nicotine dose instructions on the reinforcing and self-reported rewarding effects of smoking (original) (raw)
Related papers
Sex differences in the subjective and reinforcing effects of cigarette nicotine dose
Psychopharmacology, 2002
Rationale: Some research with novel nicotine delivery methods suggests that nicotine itself may be less reinforcing in women than in men. However, sex differences in the reinforcing effects of nicotine dose via cigarette smoking have received little attention. Objectives: Sex differences in the subjective and reinforcing effects of smoking were examined as a function of two cigarette nicotine "dose" levels (moderate-subjects' preferred brand, ‡0.7 mg yield; low-Carlton "ultralight", 0.1 mg yield). Methods: Male and female smokers (n=30) participated in three sessions, the first two involving independent assessment (only one brand available), and the third involving concurrent assessment (both brands available), of subjective ratings (e.g. "liking") and reinforcement for the two cigarette brands. Subjects were blind to the brand of each cigarette, and subjects abstained overnight prior to each session. Reinforcement was determined by responses on a computer task to earn single puffs on the designated cigarette. Results: Subjective ratings differed between the low versus moderate cigarette nicotine dose under both independent and concurrent assessment conditions, as expected. Notably, this dose difference was smaller in women than in men (i.e. significant sex by dose interactions). The dose effect on smoke reinforcement also was smaller in women than men, but only under the independent and not concurrent assessment condition. Conclusions: These results indicate that cigarette nicotine dose is a less important influence on the subjective and, under some conditions, reinforcing effects of smoking in women than in men.
Sex differences in nicotine effects and self-administration: Review of human and animal evidence
Nicotine & Tobacco Research, 1999
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. Selfadministration 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 femaies 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.
Pharmacology Biochemistry and Behavior, 2013
Despite the well-known adverse health consequences of smoking, approximately 20% of US adults smoke tobacco cigarettes. Much of the research on smoking reinforcement and the maintenance of tobacco smoking behavior has focused on nicotine; however, a number of other non-nicotine factors are likely to influence the reinforcing effects of smoked tobacco. A growing number of studies suggest that non-nicotine factors, through many pairings with nicotine, are partially responsible for the reinforcing effect of smoking. Additionally, both clinical studies and preclinical advances in our understanding of nicotinic receptor regulation suggest that abstinence from smoking may influence smoking reinforcement. These experiments were conducted for 2 reasons: to validate a MRI-compatible cigarette smoking device; and to simultaneously investigate the impact of nicotine, smoking-associated conditioned reinforcers, and smoking abstinence state on subjective ratings of smoking reinforcement. Participants smoked nicotine and placebo cigarettes through an fMRI compatible device in an overnight-abstinent state or in a nonabstinent state, after having smoked a cigarette 25 minutes prior. Outcome measures were within-subject changes in physiology and subjective ratings of craving and drug effect during the smoking of nicotine or placebo cigarettes on different days in both abstinence states. Cigarette type (nicotine vs. placebo) had a significant effect on positive subjective ratings of smoking reinforcement ("High", "Like Drug", "Feel Drug"; nicotine>placebo). In contrast, abstinence state was found to have significant effects on both positive and negative ratings of smoking reinforcement ("Crave", "Anxiety", "Irritability"; abstinence > nonabstinence). Interaction effects between abstinence and nicotine provide clues about the importance of neuroadaptive mechanisms operating in dependence, as well as the impact of conditioned reinforcement on subjective ratings of smokinginduced high.
Sex differences in conditioned nicotine reward are age-specific
Pharmacology Biochemistry and Behavior, 2015
Women constitute half of all smokers and many studies suggest that adult males and females differ in factors that maintain tobacco smoking, yet there is limited information about sex differences in nicotine reward during adolescence. Limited studies suggest that adolescent male rats selfadminister more nicotine than adults, suggesting that drug administration during adolescence leads to different behavioral effects than during adulthood. In the present study, male rats developed a significant conditioned place preference (CPP) to lower doses of nicotine than females, regardless of age. In addition, adolescents were more sensitive than adults. In female rats, adolescents exhibited a CPP of greater magnitude than adult females. In males, the magnitude of the CPP did not differ as a function of age, but adolescents exhibited CPP to lower doses than adults. There also were differences in nicotinic acetylcholinergic receptor binding in nucleus accumbens and caudate putamen in response to nicotine across age and sex. These findings suggest that it is necessary to consider sex-and age-specific effects of drugs such as nicotine when developing strategies for improving smoking cessation treatments.
Sex differences in nicotine preference
Journal of Neuroscience Research, 2016
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
Psychopharmacology, 2005
Rationale: Sex differences have been reported for the impact of nicotine and nonpharmacological cues on smoking. While nonpharmacological environmental stimuli have also been shown to influence nicotine selfadministration in rats, there have been no attempts to examine the impact of sex differences in the contributions of nicotine and nondrug stimuli to this behavior. Objectives: This experiment investigated sex differences in operant responding for nicotine in rats when drug infusions were delivered either in the absence of, or in combination with, a nonpharmacological stimulus. Methods: Initially, male and female rats acquired selfadministration for nicotine alone across a range of doses (0.03, 0.06, and 0.15 mg kg −1 inf −1 , freebase). After stable acquisition, nicotine infusions were combined with a weakly reinforcing, compound visual stimulus. Results: While there was no overall effect of dose on active lever responding for nicotine in the absence of the visual stimulus, female rats responded more on the reinforced lever than males at 0.06 and 0.15 mg kg −1 inf −1 on an FR5 schedule. However, they also showed increased responding on the nonreinforced lever compared to males at the same doses.
A double-blind placebo controlled experimental study of nicotine: I—effects on incentive motivation
Psychopharmacology, 2006
Rationale Brain reward pathways implicated in addiction appear to be less reactive in regular drug users; behavioural manifestations may include decreased sensitivity to natural reinforcers. Objectives This study aimed to replicate earlier findings of abstinence-associated incentive motivation deficits in smokers and to determine whether these can be reversed with nicotine in the form of lozenge. Methods One hundred forty-five smokers were each tested twice, once after receiving nicotine, and once after receiving placebo lozenge in counterbalanced order. Participants completed various tests of incentive motivational functioning: a measure of subjective enjoyment, the Snaith–Hamilton pleasure scale (SHAPS); a simple card sorting task, the card arranging reward responsivity objective test (CARROT) with and without financial incentive; the modified emotional Stroop test; a cue-reactivity task; and a novel reaction time task to explore effects of signals of reward, the incentive motivational enhancement of response speed task. Results Compared with performance during abstinence (placebo condition), nicotine was associated with: higher self-reported pleasure expectations on the SHAPS; enhanced responsiveness to financial reward on the CARROT in smokers who smoked 15 or more cigarettes a day; and greater interference from appetitive words on the Stroop task. Conclusions These results are generally consistent with contemporary neurobiological theories of addiction and suggest that short-term smoking abstinence is associated with impaired reward motivation which can be reversed with nicotine.
Drug and Alcohol Dependence, 2007
We have hypothesized that nicotine has two effects on reinforcement; it increases the probability of responses resulting in nicotine delivery (primary reinforcement) and enhances the apparent reward value of non-nicotine reinforcers (reinforcement enhancing effect). The present studies investigated two predictions generated by this hypothesis: 1) that the reinforcement enhancing effect will depend on apparent stimulus reward value, and 2) that the temporal profile of this effect would depend on the pharmacological profile of nicotine. In Experiment 1, rats were trained to lever press for one of two audio-visual stimuli that differed in their intrinsic reinforcing value and then the effect of presession nicotine (0.4 mg/kg base) or saline injections was tested. The stimulus that supported very low rates of operant responding displayed smaller increases in responding after pre-session injections of nicotine. In Experiment 2 the effect of nicotine injected 5 min before the session was compared to the effect of nicotine injected 1 h after the session using the more reinforcing stimulus condition from the first experiment. A control group received only vehicle injections. In contrast to nicotine injected just prior to the session, post-session injections of nicotine had no detectable effect on responding for the more reinforcing stimulus. These results indicate that the reinforcement enhancing action of nicotine depends on the intensity of the primary reinforcer and that enhanced reinforcement by nicotine depends on coincident access to a stimulus with reinforcing properties.
The American Journal on Addictions, 2013
Background and Objectives: Female smokers have greater difficulty quitting, possibly due to increased reactivity to smoking-related cues. This study assessed sex differences in craving, affect, and preference for immediate smoking after cue exposure. Methods: Regular smokers (n ¼ 60; 50% female) were exposed to smoking and neutral cues in separate, counterbalanced sessions. Outcomes included changes in craving and affect and preference for immediate smoking following cue exposure. Results: Findings indicated that women exhibited greater preference for immediate smoking (p ¼ .004), and reported greater cue-induced increases in cigarette craving (p ¼ .046) and negative affect (p ¼ .025). Discussion and Conclusions: These data suggest that women may have greater difficulty inhibiting smoking after cue exposure, possibly as a consequence of greater increases in craving and negative affect. Scientific Significance and Future Directions: Findings suggest a mechanism that may contribute to greater cessation failure among female smokers. (Am J Addict 2013;XX:1-7)