Disturbances of diurnal rhythms of biogenic amines contents in hypothalamic nuclei as an evidence of neurotropic effects of enterotropic carcinogen 1,2-dimethylhydrazine.
OBJECTIVE
Our data on the contents of norepinephrine (NE), dopamine (DA) and the metabolite of serotonin 5-hydroxyindoleacetic acid (5-HIAA) measured in the suprachiasmatic nuclei (SCN), preoptic area (PA) and median eminence (ME) of hypothalamus of rats after single subcutaneous injection of 1,2-dimethylhydrazine (DMH) as well as the effect of this carcinogen on formation of reactive oxygen species (ROS) in the PA are presented in this paper.


RESULTS
Diurnal changes of DA in all studied brain structures and of NE in the PA have been observed in the control group. Their morning levels were higher than evening ones. Rhythms of 5-HIAA in the SCN and diurnal changes of ROS formation have been shown to have contrary changes in control. Both the morning (11 a.m.) and evening (11 p.m.) subcutaneous administration of DMH at the dose of 21 mg/kg of body weight resulted in changes of all rhythms observed in control. In some cases a phase shift was found, in others the rhythms of neurotransmitters and ROS formation disappeared entirely.


CONCLUSIONS
The data obtained confirm the idea of dopaminergic and serotoninergic systems taking part in mechanisms of a response of the hypothalamic nuclei to non-photic stimuli. It is suggested that the effect of DMH on the content and diurnal rhythms of neurotransmitters in the hypothalamic structures under study is due to its affecting activities of the enzymes of biogenic amines synthesis, synaptic transmission, melatonin synthesis and secretion rhythms. The change in ROS formation that is caused by administration of DMH is likely to be due to a disturbance of diurnal rhythms of neurotransmitters that are one of the sources of formation of free radicals in the brain.
Arutjunyan
A V
AV
D.O. Ott Research Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, St. Petersburg, Russia. arutjunyan@AA3703.spb.edu
Kerkeshko
G O
GO
Anisimov
V N
VN
Stepanov
M G
MG
Prokopenko
V M
VM
Pozdeyev
N V
NV
Korenevsky
A V
AV
D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007279:Injections, Subcutaneous; D007422:Intestines / Q000187:drug effects; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*
D015306:Biogenic Monoamines; D002273:Carcinogens; D011355:Prodrugs; D017382:Reactive Oxygen Species; D006897:Hydroxyindoleacetic Acid; D019813:1,2-Dimethylhydrazine; D008550:Melatonin; D004298:Dopamine; D009638:Norepinephrine