Exposure to repeated, intermittent d-amphetamine induces sensitization of HPA axis to a subsequent stressor.
Previous studies have demonstrated that exposure to psychostimulant drugs can produce a lasting cross-sensitization to the behavioral effects of stress. The main purpose the present study was, therefore, to determine the effects of psychostimulant cross-sensitization on the stress-induced release of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Rats were given a series of injections of d-amphetamine or vehicle in a regimen that has been shown previously to induce cross-sensitization to a stressor. After two weeks, half the animals in the drug and vehicle-treated conditions were subjected to 30 min restraint stress; the remaining animals served as non-stressed controls. Animals were then sacrificed and trunk blood was assayed for CORT and ACTH. Prior d-amphetamine had no effect upon levels of CORT and ACTH in the non-stressed animals. Following 30 min restraint stress, however, levels of both hormones were significantly higher in drug-treated animals compared to controls. A second experiment confirmed behavioral sensitization to the current schedule of d-amphetamine injections, and demonstrated neuroendocrine sensitization of ACTH and CORT to a subsequent drug challenge. The augmented release of CORT and ACTH observed in d-amphetamine-treated rats might have important implications for human disorders in which processes resembling neurochemical sensitization have been hypothesized to play an etiological role.
Barr
Alasdair M
AM
Department of Psychology, 2136 West Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z4.
Hofmann
Candace E
CE
Weinberg
Joanne
J
Phillips
Anthony G
AG
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003345:Corticosterone / Q000097:blood; D003913:Dextroamphetamine / Q000008:administration & dosage*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000097:blood*
D000697:Central Nervous System Stimulants; D000324:Adrenocorticotropic Hormone; D003913:Dextroamphetamine; D003345:Corticosterone