Yohimbine administration and cue-reactivity in cocaine-dependent individuals.
BACKGROUND
Preclinical studies suggest that stress potentiates cue-induced cocaine seeking and that this effect is more pronounced in females. These findings have not been characterized in clinical populations.


OBJECTIVE
The objectives of this study were to examine the impact a pharmacological stressor, alpha-2 adrenergic receptor antagonist yohimbine, on the subjective, endocrine, and physiologic responses to drug-paired cues cocaine-dependent men and women.


METHODS
In a double-blind placebo-controlled cross-over study, cocaine-dependent men (n = 32), cocaine-dependent women (n = 30), control men (n = 32), and control women (n = 25) received either yohimbine or placebo prior to two cocaine cue exposure sessions.


RESULTS
Yohimbine increased ratings of anxiety both before (p < 0.001) and after (p = 0.035) cues, and the post-cue increase in anxiety was more pronounced in women (p = 0.001). Yohimbine also significantly increased craving, compared with placebo (p < 0.05), following the cue presentation, and this effect was greater in women than men (gender by treatment interaction; p = 0.006). Yohimbine also increased salivary cortisol (p < 0.001) and dehydroepiandrosterone (p = 0.003) levels, regardless of diagnostic group. Women had a significantly greater heart rate response following yohimbine as compared with men (p < 0.001).


CONCLUSIONS
Stress may increase the salience of cocaine cues for cocaine-dependent women as compared with men. This suggests gender differences in vulnerability to craving and relapse under stressful conditions.
Clinical Neuroscience Division, Department of Psychiatry and Behavioral Neurosciences, Medical University of South Carolina, 125 Doughty Street, Charleston, SC, 29425, USA, moranm@musc.edu.
Megan M
MM
Moran-Santa Maria
Aimee
A
McRae-Clark
Nathaniel L
NL
Baker
Viswanathan
V
Ramakrishnan
Kathleen T
KT
Brady
D058669:Adrenergic alpha-2 Receptor Antagonists; D000328:Adult; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology; D019970:Cocaine-Related Disorders / Q000523:psychology*; D066249:Craving / Q000187:drug effects*; D018592:Cross-Over Studies; D003463:Cues; D003687:Dehydroepiandrosterone / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000737:chemistry; D012727:Sex Characteristics; D015016:Yohimbine; D055815:Young Adult
D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine; D003687:Dehydroepiandrosterone; D006854:Hydrocortisone