Long-term cortisol treatment impairs behavioral and neuroendocrine responses to 5-HT1 agonists in the rat.
The effects of chronic cortisol treatment on neuroendocrine and behavioral responses to serotonin1 (5-HT1) receptor agonists were studied in conscious, freely moving rats. Seven-day cortisol treatment (25 mg/kg/day with osmotic minipumps) markedly suppressed basal plasma corticotropin (ACTH) and corticosterone concentrations, indicating a suppression of the hypothalamo-pituitary-adrenocortical axis. Cortisol also decreased body weight, food intake, plasma norepinephrine (NE), and epinephrine (E) levels. In the drug challenge studies, we used two 5-HT1 agonists, the 5-HT1B and 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), to examine the effect of cortisol on their behavioral and neuroendocrine effects. After 7-day cortisol treatment, plasma prolactin responses to both m-CPP and 8-OHDPAT were significantly decreased. While the plasma NE, E, and food intake responses to m-CPP were also significantly reduced by cortisol treatment, these same responses to 8-OHDPAT were unchanged. The effect of m-CPP on locomotor activity was also decreased. Since only the responses to m-CPP and 8-OHDPAT previously shown to be antagonized by pretreatment with the 5-HT1/5-HT2 antagonist, metergoline, were significantly attenuated after cortisol treatment, these changes may be specific to 5-HT receptors. These data indicate that chronic exposure to high glucocorticoid levels alters 5-HT1 receptor-mediated functions and provides additional evidence relevant to the contribution of glucocorticoid elevation to the symptoms of depression.
Bagdy
G
G
Section on Clinical Neuropharmacology, National Institute of Mental Health, Bethesda, Md.
Calogero
A E
AE
Aulakh
C S
CS
Szemeredi
K
K
Murphy
D L
DL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000097:blood*; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood; D010879:Piperazines / Q000494:pharmacology; D011388:Prolactin / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D002395:Catecholamines; D010879:Piperazines; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine; D003345:Corticosterone; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine