Pituitary-adrenal axis responses to acute amphetamine in the rat.
After acute administration of amphetamine (AMPH), a characteristic behavioral response occurs in the rat, involving increased locomotion and stereotyped licking, grooming, and biting. AMPH administration also activates several neuroendocrine systems, including the pituitary-adrenal axis. Because recent evidence has supported a role for glucocorticoids in modulating the behavioral response to AMPH, the purpose of the present study was to examine the relationship between behavioral and hypothalamic-pituitary-adrenal (HPA) responses to AMPH and determine the physiological substrates responsible for the AMPH-induced release of adrenal steroids. AMPH administration produced the often-reported "inverted-U" shaped behavioral response. Specifically, locomotion was increased by low doses (0.5-1.0 mg/kg, SC) significantly more so than by the highest dose (5.0 mg/kg, SC), which instead elicited intense focused stereotyped movements. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were increased by AMPH in a monotonic dose-response function, with highest levels measured in rats exhibiting the most intense stereotyped behaviors. Plasma ACTH levels then declined 10-30 min after AMPH administration, while AMPH-induced locomotion and stereotyped behavior persisted well beyond this period. In a parallel study, AMPH failed to elevate plasma levels of vasopressin, an important ACTH secretagogue, and AMPH reduced levels of corticotropin-releasing factor (CRF) immunoreactivity in the median eminence, providing indirect evidence of CRF release from this region. AMPH-stimulated ACTH and corticosterone release were prevented by immunoneutralization of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Swerdlow
N R
NR
Department of Psychiatry, UCSD School of Medicine, La Jolla 92093-0804.
Koob
G F
GF
Cador
M
M
Lorang
M
M
Hauger
R L
RL
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D014667:Vasopressins / Q000097:blood
D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000661:Amphetamine; D003345:Corticosterone