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

• Published in: American Journal of Psychiatry Vol. 169; no. 4; pp. 406 - 414
• Main Authors: Potenza, Marc N, Hong, Kwang-ik Adam, Lacadie, Cheryl M, Fulbright, Robert K, Tuit, Keri L, Sinha, Rajita
• Format: Journal Article
• Language: English
• Published: Arlington, VA American Psychiatric Publishing 01.04.2012; American Psychiatric Association
• Subjects: Addictive behaviors; Adult; Adult and adolescent clinical studies; Anxiety - physiopathology; Anxiety - psychology; Behavior, Addictive - physiopathology; Behavior, Addictive - psychology; Biological and medical sciences; Brain - physiopathology; Cocaine; Cocaine-Related Disorders - physiopathology; Cocaine-Related Disorders - psychology; Cues; Drug addiction; Female; Functional Neuroimaging - methods; Functional Neuroimaging - psychology; Gender differences; Heart Rate - physiology; Humans; Magnetic Resonance Imaging - methods; Magnetic Resonance Imaging - psychology; Male; Medical sciences; Neural Pathways - physiopathology; Neuropsychology; Psychology. Psychoanalysis. Psychiatry; Psychopathology; Psychopathology. Psychiatry; Psychotherapy; Relaxation - physiology; Relaxation - psychology; Sex Characteristics; Stress; Stress, Psychological - physiopathology; Stress, Psychological - psychology; Ester; Drug addiction; Craving; Dependence; Sex; Cocaine; Drug of abuse; Stress
• ISSN: 0002-953X; 1535-7228; 1535-7228
• DOI: 10.1176/appi.ajp.2011.11020289

Activity in brain regions linked to substance abuse was greater in cocaine-dependent women than in non-substance-abusing women after stress but not after exposure to drug-related cues. For men with cocaine dependence, the pattern was reversed: more widespread hyperactivation after drug-related cues than after stress. Clinical possibilities include targeted treatment for cocaine dependence: stress reduction for women and 12-step or cognitive-behavioral approaches for men. 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.