Long-term treatment with the antidepressants fluoxetine and desipramine potentiates endocrine responses to the serotonin agonists 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) and (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI).
Various endocrine responses to 5-hydroxytryptamine (serotonin, 5-HT) agonists were used to assess serotonergic receptor function after chronic treatment with the antidepressants fluoxetine (10 mg/kg), a 5-HT uptake blocker and the norepinephrine uptake blocker desipramine (DMI, 5 mg/kg). Both were injected (i.p.) once a day for 21 days. DOI (5-HT1C/2 agonist, 0-5 mg/kg i.p.) and 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) (less selective, but predominantly a 5-HT1C agonist, 0-20 mg/kg i.p.) were administered 18 hr after the final antidepressant injection and 30 min before decapitation. Chronic treatment with both fluoxetine and DMI produced a potentiation in most hormone responses to the 5-HT agonists (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane HCl (DOI) and MK-212, although there were several differences in individual hormone responses to the two 5-HT agonists. Fluoxetine and DMI potentiated the MK-212- and DOI-induced increase of plasma oxytocin levels and potentiated the effect of DOI on plasma adrenocorticotropic hormone (corticotropin) and prolactin levels. In contrast, the effect of the high dose of MK-212 on plasma prolactin concentration was reduced by both antidepressants. Only MK-212 increased vasopressin levels and this effect was potentiated by fluoxetine, but not by DMI. Fluoxetine also significantly increased the resting level of plasma vasopressin. DMI potentiated the effect of MK-212 on plasma renin concentration. Pretreatment with fluoxetine significantly increased (38%) the Bmax for the 5-HT1C/2 agonist sites ([125I]DOI) in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois.
Q
Q
Li
M S
MS
Brownfield
G
G
Battaglia
T M
TM
Cabrera
A D
AD
Levy
P A
PA
Rittenhouse
L D
LD
van de Kar
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000662:Amphetamines / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology*; D006728:Hormones / Q000097:blood*; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood
D000662:Amphetamines; D006728:Hormones; D011719:Pyrazines; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D014667:Vasopressins; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D000324:Adrenocorticotropic Hormone; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003891:Desipramine