Biomedical subjects
Publications and source records attributed to E V Beĭer.
An analysis of the presently available data shows that the principal pineal hormone melatonin is capable of influencing, both directly and indirectly, the state of the immune system. The immunotropic activity of this hormone can account for the stress-protective, antitumor, and antiviral effects of melatonin.
The administration of depressant reserpine and antidepressant imipramine in rats is manifested by opposite trends in the chronobiological aspect of behavior. Reserpine disorganizes the circadian locomotion rhythm and increases the rhythmological index of depression in the forced swim test. In contrast, imipramine increases the circadian rhythm contrast and decreases the index of depression. A bilateral lesion of the dorsal hippocampus attenuates both pharmacological effects, but the general trend has an antidepressant character: the effect of reserpine decreases, while the effect of imipramine increases. It is suggested that hippocampus probably plays an important role in the origin of depression and related chronobiological manifestations.
After chronic administration of beta-adrenoblocker propranolol (1 mg/kg, 14 days) reorganization of time course of forced swimming with decrease of rhythmical index of depression was observed. Pinealectomy slightly attenuated, and melatonin (1 mg/kg) potentiated this effect. As proposed, antidepressive properties of beta-adrenoblockade primarily are not connected with pharmacological denervation of the pineal gland.
Repeated stress under forced swim test conditions suppresses most of the immunological characteristics in rats. Diazepam and melatonin (both in a dose of 0.1 mg/kg), while not changing significantly the immunological state of intact animals, decrease the stress-induced shifts. The immunotropic effect of melatonin is much more pronounced than that of diazepam.
As shown, there are direct and reverse functional connections between nervous and immune systems. Different shifts in psychoemotional reactivity induced by chronic stress or mental depression are accompanied with immunological disturbance, and on the contrary, disorders of immune state may be source of changes in mental functions. The pineal hormone melatonin, anxiolytic and antidepressant drugs simultaneously influences on the cerebral structures and immune system. These effects may be important part of specific psychopharmacological activity of the drugs.
The immune system activity has a rhythmicity with circadian and seasonal periods. Some reviewed data shown that fluctuations of different immunological parameters may be result of rhythmical activity of the pineal gland.
The review summarizes recent data about the modulatory influence of pineal and extrapineal melatonin on the production and function of the main blood cells (erythrocytes, trombocytes and leucocytes).
The chronic administration of pineal hormone melatonin (1 mg) in healthy humans leads to a significant increase in the hemoglobin level and erythrocyte number, especially on the background of low values of both indices. Melatonin also modulates the leukocyte number and morphological characteristics of leukocytes.
Daily variations in the heart rate were studied. Chronic treatment with propranolol attenuated the sympathetic tone only at night and promoted acrophase in the morning. The complete lesion of suprachiasmatic nuclei balanced the circadian rhythm of the heart rate variability and the effect of drug.
The main parameters and rhythmicity of the forced swimming, including the rhythmical index of depression, had great daily variations. The beta-adrenoblocker anapriline changed the temporal dynamics of swimming and decreased the depression index. The peak effect was shown in the daytime after an acute administration of the drug. After chronic administration, the peak pharmacological activity changed during morning hours.
A chronobiological evaluation of the forced swimming test in rats treated with propranolol has shown that beta-adrenoblockers have antidepressive properties. This is true for oxprenolol which shows less pronounced affects. Nadolol that does not readily cross the blood-brain barrier insignificantly changes swimming behavior in the animals.
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Acute administration of propranolol, 1 mg/kg i.p., decreased the amplitude of locomotor circadian rhythm in rats and shifted its acrophase to late night hours. After chronic (10-day) treatment with the drug, morning rises in locomotion after turning out the light became less frequent. The circadian rhythm reorganization observed may depend on the effects of the beta-adrenoblocker on its specific receptors in the hypothalamic suprachiasmatic nuclei and/or the pineal gland.
After chronic administration of propranolol (1 and 5 mg/kg) to rats for 14 days, the time course of forced swimming was changed, by decreasing the rhythmic index of depression. With propranolol, the depressogenic properties of reserpine and clonidine were attenuated. The antidepressive activity of propranolol was associated with cerebral beta-adrenoceptor block.
Bilateral striatectomy disorganized the rhythmical structure of forced swimming and circadian motility of rats. Destruction of dorsal but not ventral striatum eliminated the effect of beta-adrenoblocker propranolol on temporal organization of behaviour. The results suggest that just the dorsal striatum is mainly subjected to adrenergic control.
Pinealectomy and electrolytic destruction in different directions changed the behaviour of rats in a conflict situation and the temporal organization of forced swimming. Combination of both kinds of surgery decreased the behavioural shifts produced by the hippocampal lesions. It is suggested that the anti-stressor properties of the pineal gland can be realized through changes in the hippocampal function state.
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Bilateral lesions of the hippocampus induced irregular shifts of the heart rate variability in rats. The shifts could be prevented with melatonin but not with diazepam.