Neuroendocrine-related effects of long-term, 'binge' cocaine administration: diminished individual differences in stress-induced corticosterone response.
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 (3x15 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.
Sarnyai
Z
Z
Laboratory of Neuroendocrinology, The Rockefeller University, New York, N.Y., 10021, USA. sarnysz@rockvax.rockefeller.edu
Dhabhar
F S
FS
McEwen
B S
BS
Kreek
M J
MJ
D000704:Analysis of Variance; D000818:Animals; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003345:Corticosterone / Q000378:metabolism*; D004334:Drug Administration Schedule; D007206:Individuality; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012636:Secretory Rate; D013312:Stress, Physiological / Q000503:physiopathology*; D013997:Time Factors
D003345:Corticosterone