Neuroendocrine-related effects of long-term, 'binge' cocaine administration: diminished individual differences in stress-induced corticosterone response

Sarnyai, Zoltán, Dhabhar, Firdaus S., McEwen, Bruce S., and Kreek, Mary Jeanne (1998) Neuroendocrine-related effects of long-term, 'binge' cocaine administration: diminished individual differences in stress-induced corticosterone response. Neuroendocrinology, 68 (5). pp. 334-344.

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Abstract

Acute cocaine administration activates behavioral and neuroendocrine processes associated with the stress response. However, much less is known about the effects of chronic, long-term cocaine administration on neuroendocrine adaptations and individual vulnerability to stress. We hypothesized that chronic 'binge' cocaine administration may serve as a chronic pharmacological stressor leading to a hyperactivity of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis and alterations in its feedback mechanisms. In order to test this hypothesis, the effects of long-term (3 and 6 weeks) 'binge' pattern cocaine administration (3×15 mg/kg cocaine, i.p., daily, during the early phase of the light cycle) on body weight, adrenal gland weight, basal and stress-induced activity of the corticosterone (CORT) and basal plasma testosterone (T) levels were measured. Both 3 and 6 weeks 'binge' cocaine administration decreased body weight gain, increased the weight of adrenal glands and increased basal CORT levels. Plasma T levels were suppressed by both 3 and 6 weeks of cocaine treatment. No correlation was found between elevated CORT and low T levels at any time point. Neither chronic saline nor cocaine administration altered stress-induced CORT secretion. CORT levels 60 min following the restraint stress (recovery) were significantly lower than pre-stress basal levels after 3 and 6 weeks of cocaine, but not saline, administration. Moreover, initial individual differences in stress-induced CORT response, i.e. low and high responsivity to restraint prior to any saline or cocaine injections, were maintained in control rats but became diminished in cocaine-treated rats. These results indicate that chronic binge cocaine administration leads to sustained activation of the HPA axis and alters processes underlying individual vulnerability to stress.

Item ID: 35114
Item Type: Article (Research - C1)
ISSN: 1423-0194
Keywords: cocaine; adrenal steroids; stress; corticotropin; corticotropin-relasing hormone
Funders: A.V. Davis Fellowship, National Alliance for Research on Schizophrenia and Depression (NARSAD), National Institute of Health (NIH), USA
Projects and Grants: NARSAD Young Investigator Award, NIH MH41256, NIH DA05130, NIH DA00049
Date Deposited: 28 Aug 2014 23:53
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 80%
92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920414 Substance Abuse @ 20%
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