Effects of chronic 'Binge' cocaine administration on plasma ACTH and corticosterone levels in mice deficient in DARPP-32.
The product of the DARPP-32 gene mediates intracellular signals initiated by the binding of dopamine to its receptors. Cocaine administration leads to increased activation of dopamine receptors, and causes activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis. We determined the effects of chronic 'binge' pattern cocaine on HPA activity in mice containing a targeted disruption of the DARPP-32 gene. Mice received three daily injections of cocaine (15 mg/kg/injection) for 14 days, and were sacrificed 30 min after the last injection. We measured the levels of plasma adrenocorticotropin (ACTH) and corticosterone which reflect HPA activity. In wild-type controls, 'binge' cocaine administration significantly increased plasma ACTH and corticosterone levels. In contrast, DARPP-32-deficient mice failed to show a significant elevation of either plasma ACTH or corticosterone levels following 'binge' cocaine. The results indicate that DARPP-32 plays a role in mediating the stimulatory effects of cocaine on the HPA axis.
Zhou
Y
Y
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, N.Y., USA.
Schlussman
S D
SD
Ho
A
A
Spangler
R
R
Fienberg
A A
AA
Greengard
P
P
Kreek
M J
MJ
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D002908:Chronic Disease; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004334:Drug Administration Schedule; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins / Q000235:genetics*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000324:Adrenocorticotropic Hormone; D003042:Cocaine; D003345:Corticosterone