title: 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.
  
  
  METHODS
  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.
authors.affiliation: Yale Unive rsity Schoolof Medicine, New Haven, Conn., USA. marc.potenza@yale.edu
authors.forename: Marc N
authors.initials: MN
authors.lastname: Potenza
authors.forename: Kwang-ik Adam
authors.initials: KI
authors.lastname: Hong
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Lacadie
authors.forename: Robert K
authors.initials: RK
authors.lastname: Fulbright
authors.forename: Keri L
authors.initials: KL
authors.lastname: Tuit
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
mesh_terms: D000328:Adult; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology; D016739:Behavior, Addictive / Q000503:physiopathology* / Q000523:psychology*; D001921:Brain / Q000503:physiopathology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology*; D003463:Cues; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000523:psychology; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D012063:Relaxation / Q000502:physiology / Q000523:psychology; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology