Hypothalamic-pituitary-adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states.
BACKGROUND
Environmental stimuli associated with cocaine are known to elicit drug craving and increase the likelihood of relapse. However, the psychobiological changes that occur with exposure to these stimuli and in episodes of drug craving are not well understood. This study examined the response of brain stress circuits to environmental stimuli that are known to increase cocaine craving in cocaine dependent individuals.


METHODS
Fifty-four treatment seeking cocaine dependent individuals, who were admitted to an inpatient treatment research unit for 2-4 weeks, participated in three laboratory sessions. Subjects were exposed to a brief 5-min guided imagery procedure that involved imagining a recent personal stressful situation, a drug-related situation and a neutral-relaxing situation, one imagery per session presented in random order. Subjective ratings of craving and anxiety, cardiovascular measures, and plasma levels of adrenocorticotrophic hormone (ACTH), cortisol, prolactin, norepinephrine (NE) and epinephrine (EPI) were assessed.


RESULTS
Exposure to stress and to drug cues each resulted in significant increases in cocaine craving and subjective anxiety, pulse rate, systolic blood pressure, ACTH, cortisol, prolactin and NE as compared to the response to neutral imagery. In addition, stress imagery also increased diastolic blood pressure and plasma EPI as compared to responses to the drug cue imagery and neutral-relaxing imagery.


CONCLUSIONS
The findings indicate a significant activation of the CRF-HPA axis and noradrenergic/sympatho-adreno-medullary (SAM) system response during stress-induced and drug cue induced cocaine craving states in cocaine dependent individuals. The role of stress system activation in cocaine craving and in cocaine use is discussed.
Sinha
Rajita
R
Department of Psychiatry, Yale University School of Medicine, S-112 Substance Abuse Center, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA. rajita.sinha@yale.edu
Talih
Makram
M
Malison
Robert
R
Cooney
Ned
N
Anderson
George M
GM
Kreek
Mary Jeanne
MJ
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001007:Anxiety / Q000209:etiology / Q000523:psychology; D001794:Blood Pressure / Q000502:physiology; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000523:psychology*; D003463:Cues; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011388:Prolactin / Q000097:blood; D013315:Stress, Psychological / Q000150:complications* / Q000523:psychology; D013997:Time Factors
D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine