Jm. Odonnell et M. Grealy, NEUROENDOCRINE RESPONSE TO CLONIDINE AND 8-OH-DPAT IN RATS FOLLOWING CHRONIC ADMINISTRATION OF DESIPRAMINE OR SERTRALINE, British Journal of Pharmacology, 105(4), 1992, pp. 863-868
1 Rats were administered either desipramine (DMI) or sertraline daily
at doses 7.5 mg kg-1 or 10 mg kg-1, i.p., respectively and the effects
on the functional state of hypothalamic neuroendocrine control mechan
isms assessed by measurements of plasma hormones following acute drug
challenge. The effects of treatment on gross behaviour and brain adren
oceptor density were also determined. 2 Both DMI and sertraline caused
significant reduction in activity measured as ambulation and rearing
at 14 days of treatment. 3 All animals were chronically cannulated aft
er 14 days of treatment and tested for neuroendocrine response to acut
e i.v. clonidine (50-mu-g kg-1) or 8-hydroxy-2-(di-n-propylamino)tetra
lin (8-OH-DPAT, 250-mu-g kg-1) after 21 or more days of treatment. 4 R
ats treated with DMI but not sertraline showed a virtually complete su
ppression of the growth hormone (GH) secretion elicited by clonidine i
n controls, while the secretion of corticosterone was augmented. 5 Tre
atment with DMI but not sertraline led to a significantly greater 8-OH
-DPAT-induced secretion of prolactin than in the control rats, while t
he plasma concentrations of corticosterone following 8-OH-DPAT were no
t influenced by either DMI or sertraline treatment. 6 The density (but
not the affinity) of cerebral cortical binding of [H-3]-dihydroalpren
olol was significantly reduced by DMI treatment. 7 These results show
that DMI treatment blunted the sensitivity of post-synaptic alpha(2)-a
drenoceptors, accompanied by complex interactions manifested as increa
sed responsiveness of alpha(1)-adrenoceptors and 5-HT1A receptors. Ser
traline had no significant neurendocrine effects at a dose which signi
ficantly reduced gross activity.