Community-dwelling cocaine-dependent men and women respond differently to social stressors versus cocaine cues

Abstract

Summary There are likely to be gender differences in determinants of relapse to drug use following abstinence in cocaine-dependent individuals. Cocaine-dependent women are more likely to attribute relapse to negative emotional states and interpersonal conflict. Cocaine dependence has also been linked to dysregulation of stress response and the hypothalamic pituitary adrenal (HPA) axis which may differ between genders. Subjective and HPA axis responses to a social evaluative stressor, the Trier Social Stress Test (TRIER), and in vivo cocaine-related cues were examined in the present study. Results There were no gender differences in magnitude of craving responses to the TRIER or the CUE. Both genders had a greater craving response to the CUE than to the TRIER, but the magnitude of the difference was greater for men than women (p=0.04). Cocaine-dependent subjects, compared to the control group, had significantly higher response throughout the TRIER (p<0.0001) and CUE (p<0.0001) testing sessions. There were no gender differences and no gender by cocaine interaction for ACTH responses to the TRIER, although women had lower baseline ACTH (p=0.049). On the CUE task, in contrast, female cocaine-dependent subjects had a more blunted ACTH response than did the other three groups (p=0.02). Female cocaine-dependent subjects also had a lower odds of a positive cortisol response to the TRIER as compared to the other three groups (OR=0.84, 95% CI=[0.02, 1.01]). During the CUE task, cocaine-dependent subjects had overall higher mean cortisol levels (p=0.0001), and higher odds of demonstrating a positive cortisol response to the CUE (OR=2.61, 95% CI=[1.11, 6.11]). No gender differences were found in ACTH responses to the CUE. The results are reviewed in the context of the existing literature on gender differences in cocaine dependence and potential implications for treatment are discussed.

Yohimbine administration and cue-reactivity in cocaine-dependent individuals

“…This is particularly important since stress and drug-cues have traditionally been treated as independent factors in the clinical relapse process (Sinha et al 2000). Although clinical studies of cocaine-dependent individuals suggest that stress is a significant risk factor for relapse in women (Back et al 2005; McKay et al 1996; Waldrop et al 2009), the findings of the present study suggest that the stress-relapse connection is more complex and stress may enhance the salience of cocaine cues for cocaine-dependent women. As such, this study supports the idea that stress followed by drug-related cues could enhance the likelihood of relapse and provides a reasonable human laboratory model to explore sex differences in the stress-cue-relapse connection.…”

“…Thus, the increase in adrenal steroid levels found in this study was not surprising. Since drug cues also increase NA and HPA axis activity in cocaine-dependent individuals, we expected that cocaine-dependent subjects would exhibit exacerbated heart rate and adrenal steroid responses to yohimbine and the drug cue (Sinha et al 2003; Waldrop et al 2009). However, there were no group differences in the magnitude of the physiologic or endocrine responses to the stressor and the drug cue.…”

“…Although both have been studied separately, few studies have investigated their interaction, especially in cocaine-dependent individuals. Moreover, although both stress and cue reactivity differ in cocaine-dependent men and women (Back et al 2005; Fox et al 2006; McKay et al 1996; Waldrop et al 2009), few studies have examined the relationships between drug-related cues and stress in men versus women.…”

“…Compared with cocaine-dependent men, cocaine-dependent women report greater stress and nervousness in response to laboratory stress tasks (Back et al 2005; Waldrop et al 2009). In rodents, female animals exhibit greater drug seeking behavior in response to pharmacological stressors than male rodents (Anker and Carroll 2010; Buffalari et al 2012).…”

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

“…Higher levels of estrogens, and lower levels of progesterone, are associated with greater sensitivity to the euphorigenic properties of cocaine in women (Evans 2007). This increased sensitivity may contribute to why women, compared with men, start using cocaine regularly at a younger age (Chen and Kandel 2002), transition from use to abuse more quickly (McCance-Katz et al 1999), experience greater craving in response to drug-associated cues (Robbins et al 1999) and stress (Potenza et al 2012;Waldrop et al 2012), and exhibit more severe drug-seeking behavior upon relapse (Gallop et al 2007). In contrast, more women than men remain abstinent after treatment (Weiss et al 1997).…”