Effects of noradrenaline and serotonin reuptake inhibitors on pituitary-adrenocortical and sympatho-adrenomedullar system of adult rats.
OBJECTIVE
To estimate the influence of long-term treatment with noradrenergic and serotonergic reuptake inhibitors on activity of pituitary-adrenocortical and sympatho-adrenomedullar systems in animals, we compared the effects of maprotiline (a selective inhibitor of noradrenaline reuptake) and fluxilan (a selective inhibitor of serotonin reuptake) on plasma noradrenaline (NA), adrenaline (A), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels in unstressed control and rats exposed to chronic unpredictable mild stress (CUMS).


METHODS
Plasma NA and A were assayed by a radioenzymatic method. Plasma CORT was measured using RIA kits and plasma ACTH by a chemiluminescent method.


RESULTS
CUMS did not affect blood plasma NA, A and ACTH content, but elevated plasma CORT level. Maprotiline elevated plasma NA content both in unstressed control and CUMS group, whereas plasma A remained unchanged. Fluxilan acted significantly increasing plasma NA and A concentrations both in control and CUMS rats. Neither maprotiline nor fluxilan affected plasma ACTH level both in unstressed control and CUMS animals. Plasma CORT level in unstressed control rats remained unchanged after maprotiline and fluxilan treatment, while being significantly decreased in CUMS rats.


CONCLUSIONS
Chronic treatment of adult rat males with maprotiline, a noradrenaline reuptake inhibitor activated sympathoneural system. On the other hand, fluxilan, a serotonin reuptake inhibitor activated both sympathoneural and adrenomedullar system, whereas both antidepressants desensitized HPA axis. The findings described here suggest that elevated plasma catecholamines my contribute to adverse effects of these drugs on cardiovascular parameters during antidepressant therapy.
Dronjak
Sladjana
S
Institute of Nuclear of Sciences 'Vinca', Laboratory of Molecular Biology and Endocrinology, 11000 Belgrade, Serbia. sladj@vin.bg.ac.yu
Spasojevic
Natasa
N
Gavrilovic
Ljubica
L
Varagic
Vladislav
V
D000313:Adrenal Medulla / Q000187:drug effects / Q000502:physiology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004837:Epinephrine / Q000097:blood*; D005473:Fluoxetine / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008376:Maprotiline / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013315:Stress, Psychological / Q000097:blood*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D018759:Adrenergic Uptake Inhibitors; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D004837:Epinephrine; D005473:Fluoxetine; D008376:Maprotiline; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors