Prior chronic exposure to cocaine inhibits the serotonergic stimulation of ACTH and secretion of corticosterone.
The effect of long-term pretreatment with cocaine on serotonergic regulation of ACTH (adrenocorticotropic hormone; corticotropin) and secretion of corticosterone in rats was investigated. The following observations were made: (1) Pretreatment with cocaine had no significant effect on basal levels of ACTH and corticosterone in plasma. However, cocaine caused a reduction in the ability of the 5-HT (5-hydroxytryptamine, serotonin) releaser p-chloroamphetamine (PCA) to increase corticosterone in plasma, 42 hr after the last injection of cocaine. (2) Exposure to cocaine for 7 days was sufficient to produce a maximal inhibition of the PCA-induced increase in ACTH in plasma. (3) The inhibitory effect of cocaine on PCA-induced release of ACTH was more marked than on corticosterone. (4) Conversely, the dose-dependent stimulatory effect of two 5-HT1 agonists, RU 24969 (5-methoxy-3-(1,2,3,4-tetrahydro-4-pyridinyl)-1H-indole) and m-CPP (m-chlorophenylpiperazine), on ACTH and corticosterone was not reduced by 7 days of exposure to cocaine. Taken together, these findings indicate that pretreatment with cocaine reduced the function of serotonergic nerve-terminals but not postsynaptic receptors, that stimulate ACTH and secretion of corticosterone.
Van de Kar
L D
LD
Department of Pharmacology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153.
Bonadonna
A M
AM
Rittenhouse
P A
PA
Kerr
J E
JE
Levy
A D
AD
Iyer
L
L
Herbert
G B
GB
Alvarez Sanz
M C
MC
Lent
S J
SJ
Carnes
M
M
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000502:physiology*; D013997:Time Factors; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D012701:Serotonin; D010133:p-Chloroamphetamine; D000324:Adrenocorticotropic Hormone; D003042:Cocaine; D003345:Corticosterone