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

Zoltán Sarnyai, Firdaus S. Dhabhar, Bruce S. McEwen, Mary Jeanne Kreek

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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 x 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.

Original languageEnglish (US)
Pages (from-to)334-344
Number of pages11
Issue number5
StatePublished - 1998
Externally publishedYes


  • Adrenal steroids
  • Cocaine
  • Corticotropin
  • Corticotropin-releasing hormone
  • Stress

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Neuroendocrine-related effects of long-term, 'binge' cocaine administration: Diminished individual differences in stress-induced corticosterone response'. Together they form a unique fingerprint.

Cite this