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

Acute cocaine administration activates behavioral and neuroendocrine proces ses 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 ch ronic '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) 'b inge' pattern cocaine administration (3 x 15 mg/kg cocaine, i.p., daily, du ring the early phase of the light cycle) on body weight, adrenal gland weig ht, basal and stress-induced activity of the corticosterone (CORT) and basa l 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 suppre ssed by both 3 and 6 weeks of cocaine treatment. No correlation was found b etween elevated CORT and low T levels at any time point. Neither chronic sa line 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 t o any saline or cocaine injections, were maintained in control rats but bec ame 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.