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Neurobiology of Stress and Cocaine Addiction: Studies on Corticotropin‐Releasing Factor in Rats, Monkeys, and Humans a
Author(s) -
SARNYAI ZOLTÁN
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb09011.x
Subject(s) - addiction , psychology , corticotropin releasing hormone , neuroscience , clinical psychology , hypothalamus
Stress may contribute to the increased vulnerability to and the development of cocaine addiction. Corticotropin-releasing factor (CRF) activates the hypothalamic-pituitary-adrenal (HPA) axis as well as behavioral and immune processes in response to different environmental and pharmacologic stressors. We hypothesized that CRF might mediate some of the effects of cocaine and as such it may be a link between stressful events and increased vulnerability to cocaine addiction. We demonstrated that blockade of endogenous CRF by a CRF antiserum or a receptor antagonist prevented the cocaine-induced corticosterone response in rats. In male rhesus monkeys and in humans, cocaine selectively increased the amplitude-related, CRF-dependent, elements of pulsatile ACTH release. Cocaine-induced locomotor hyperactivity was antagonized by intracerebroventricular (i.c.v.) administration of a CRF antiserum and a CRF receptor antagonist in rats. In rhesus monkeys, strong correlations were found between behavioral hyperactivity and CRF-dependent elements of pulsatile activity of the HPA axis. Acute cocaine administration induced dose- and time-dependent alterations in hypothalamic and extrahypothalamic/limbic CRF concentrations in rats. Cocaine withdrawal elicited anxiety-like behavior and alterations of CRF concentration in the hypothalamus, amygdala, and basal forebrain. CRF antiserum (i.c.v.) antagonized anxiety-like behavior related to cocaine withdrawal. These data strongly suggest that the HPA axis, brain CRF in particular, may mediate some of the neuroendocrine and behavioral effects of cocaine. The potential involvement of CRF and HPA axis in cocaine-induced psychopathology is hypothesized.