Neural Correlates of Stress-Induced and Cue-Induced Drug Craving: Influences of Sex and Cocaine Dependence

Abstract

Objective Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. Method Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine-dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). Results Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral-relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. Conclusions In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction.

Brain Activity During Cocaine Craving and Gambling Urges: An fMRI Study

“…This indicates that the videos increased urges to use drugs or gamble in content-and diagnostic groupspecific manners. However, gender-related main or interactive effects in self-reported cravings or urges were not observed, consistent with prior reports in CD (Li et al, 2005;Potenza et al, 2012). Indeed, despite a common stereotype that women may be more 'emotional' relative to men (eg, Timmers et al, 2003), similarities in self-reported emotion are common (see Barrett and Bliss-Moreau, 2009 for review).…”

“…Furthermore, we hypothesized that activity in regions previously implicated in drug cravings and gambling urges in CD and PG, including mPFC, ACC, striatum and insula, would be sensitive to diagnostic group and video type (eg, with CD participants showing greater activation in relation to cocaine videos). We also expected that some of these regions may show additional gender-related differences (ie, gender × diagnosis × video type interaction, as has been seen in cravings in CD; Potenza et al, 2012).…”

“…Furthermore, women with CD or PG are more likely to suffer from co-occurring depression and anxiety compared with men with these disorders (Granero et al, 2009;Greenfield et al, 2010;McCance-Katz et al, 1999). Finally, in CD, gender-differences have been reported in response to pharmacological treatments (Kosten et al, 1993;Pettinati et al, 2008) as well as in craving-related brain activations (Kilts et al, 2004;Li et al, 2005;Potenza et al, 2012), although the pattern of differences has been inconsistent. Considering gender-related influences on the neural correlates of craving/urge states may: (1) help resolve and better understand some of the apparent differences observed across studies to date; and (2) provide insight into genderrelated differences in brain function that might relate to important clinical differences observed in PG and CD.…”

Individual Differences in Attentional Bias Associated with Cocaine Dependence Are Related to Varying Engagement of Neural Processing Networks

“…Recent functional neuroimaging studies have sought to characterize the neural processing events that underlie attentional bias related to drug dependence as a means of understanding the mechanisms of relapse. Such study designs are distinct from those exploring the neural correlates of drug cue reactivity in the absence of assessing their cognitive bias properties by task interference effects (Kilts et al, 2001;Potenza et al, 2012). For nicotine-dependent individuals, the level of attentional bias for smoking-related cues was positively correlated with activation of the limbic, paralimbic, and occipital brain regions associated with emotional salience, memory recall, interoceptive states, and visual processing (Janes et al, 2010).…”

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).…”