Disturbances of diurnal rhythms of biogenic amines contents in hypothalamic nuclei as an evidence of neurotropic effects of enterotropic carcinogen 1,2-dimethylhydrazine.

OBJECTIVES: 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. CONCLUSION: 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.

The effects of melatonin and L-DOPA on the diurnal rhythms of free amino acids content in the rat retina.

The effects of melatonin and dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) intraperitoneal administration on the rhythms of free amino acids content in the retina of rats were studied. The authors found that the levels of those amino acids, which are protein constituents but not neurotransmitters in the rat retina, change diurnally with maximum at 3-6 h after light onset. Diurnal changes of Ala, Arg, Asn, Ile, Met, Ser, Trp, and Val content persisted in the retina of rats maintained at constant darkness. This fact confirms the true circadian nature of these rhythms. Constant lighting abolished diurnal changes of the content of all amino acids with the exception of Trp. Daytime but not nighttime administration of melatonin decreased the levels of Ala, Asn, Gln, Ile, Met, and Ser down to nocturnal values. Diurnal changes of amino acids content vanished in melatonin-injected rats. The effect of melatonin administration disappeared when the protein synthesis was inhibited by cycloheximide. The effect of intraperitoneal administration of L-DOPA on the levels of free amino acids was opposite the effect of melatonin administration. L-DOPA increased nocturnal levels of Gly, Thr, Trp, and Val but had no effect on the daytime amino acids content. As in the case of melatonin administration, significant diurnal changes of amino acid levels disappeared in L-DOPA-injected rats. The authors hypothesize that melatonin and dopamine can serve as zeitgebers-antagonists of amino acids content rhythms in the rat retina.

Diurnal changes of tyrosine, dopamine, and dopamine metabolites content in the retina of rats maintained at different lighting conditions.

The aim of the study was to investigate the daily rhythms of tyrosine (Tyr), dopamine (DA), 3,4-dioxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) content in the retina of rats maintained under different lighting conditions. Studied substances were measured by highly sensitive high-performance liquid chromatography (HPLC) with an electrochemical detection method. It was found that the levels of Tyr, DA, DOPAC, and HVA change diurnally in the retina of adult Wistar rats maintained under standard cyclic lighting (12-h light/12-h dark). The maximum was found during the light phase of 12:12 light:dark photoperiod. Diurnal changes of DA, DOPAC, and HVA persisted in constant darkness. When the rats were maintained in constant lighting conditions for 2 d (light intensity, 200 lx), the rhythms of tyrosine, DA, and DOPAC completely disappeared. However the level of HVA was higher during the subjective day. The presence of diurnal rhythm of melatonin content in the retina of rats was confirmed by HPLC with an amperometric detection method. Since the presence of time cues is not necessary for manifestation of diurnal changes of DA and its metabolite content, it was concluded that the circadian oscillator drives these rhythms. Probably DA can serve as a zeitgeber for retinal circadian rhythms.