Sex-specific dissociations in autonomic and HPA responses to stress and cues in alcohol-dependent patients with cocaine abuse

Alcohol Alcohol. Nov-Dec 2009;44(6):575-85. doi: 10.1093/alcalc/agp060. Epub 2009 Sep 30.


Aims: Chronic alcohol and drug dependence leads to neuroadaptations in hypothalamic-pituitary-adrenal (HPA) and sympathetic adrenal medullary (SAM) stress systems, which impact response sensitivity to stress and alcohol cue and facilitates risk of relapse. To date, gender variations in these systems have not been fully assessed in abstinent alcohol-dependent individuals who also met criteria for cocaine abuse.

Methods: Forty-two (21 M/21 F) early abstinent treatment-seeking substance-abusing (SA) men and women and 42 (21 M/21 F) healthy control (HC) volunteers were exposed to three 5-min guided imagery conditions (stress, alcohol/drug cue, neutral relaxing), presented randomly, one per day across three consecutive days. Alcohol craving and anxiety ratings were obtained as well as measures of heart rate (HR), blood pressure, plasma ACTH, cortisol, norepinephrine (NE) and epinephrine (EPI).

Results: SA males showed increased ACTH and EPI basal tone compared with HC males and SA females. However, they demonstrated no increase in ACTH and cortisol levels following stress and alcohol cue imagery exposure compared to the neutral condition. SA females demonstrated a typically increased stress response in both measures. In addition, SA males showed no increase in cardiovascular response to either stress or cue, and no increase in catecholamine response to cue compared with their response to neutral imagery. Again, this dampening was not observed in HC males who produced significantly higher levels of cue-related HR and EPI, and significantly higher stress-related DBP. In contrast, SA females showed an enhanced ACTH and cortisol response to stress and cue compared with neutral imagery and this was not observed in the HC females. They also demonstrated a reduced increase in NE and EPI compared with both SA males and HC females as well as reduced HR compared with HC females.

Conclusions: While SA males showed a generalized suppression of HPA, SAM system and cardiovascular markers following both stress and cue, SA women demonstrated a selective sympatho-adrenal suppression to stress only and an enhanced HPA response to both stress and cue. These gender variations are discussed in terms of their potential impact on relapse vulnerability and treatment outcome.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Alcoholism / complications
  • Alcoholism / physiopathology*
  • Alcoholism / psychology
  • Autonomic Nervous System / physiology
  • Blood Pressure / physiology
  • Cocaine-Related Disorders / complications
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / psychology
  • Cues*
  • Female
  • Heart Rate / physiology
  • Humans
  • Hypothalamo-Hypophyseal System / physiology*
  • Male
  • Pituitary-Adrenal System / physiology*
  • Sex Characteristics*
  • Stress, Psychological / complications
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology


  • Adrenocorticotropic Hormone