Variability of the effect of atristamine and imipramine on the depressive behavior of mice in the aspect of circadian factors




2-methyl-3-(phenylaminomethyl)-1H-quinolin-4-one, atristamine, imipramine, the tail suspension test, circadian rhythms, cosinor analysis


Chronophysiological features of secretion of some hormones and neurotransmitters (especially melatonin), which have distinct circadian and seasonal rhythms, are the main endogenous factors affecting the depressive behavior of both animals and humans. That is why it is possible to assume different sensitivity of the CNS in animals to the effect of antidepressant chemicals introduced in different phases of the day.

Aim. To study the variability of the effect of a promising antidepressant atristamine in comparison with the classical tricyclic antidepressant imipramine on the depressive behavior of mice taking into account chronophysiological (circadian) factors.

Materials and methods. The depressive behavior of mice was studied using the tail suspension test. Four experiments were performed within one day at the following time intervals: 2:00-4:00, 8:00-10:00, 14:00-16:00, 20:00-22:00. The cosinor analysis of the results was carried out using the Cosinor-Analisis 2.4 program.

Results. There were no significant differences during the day among the indicators of the intact control group. Animals treated with imipramine (25 mg/kg) had a lower total time of immobility (a marker of the antidepressant activity) in all time periods. In the daytime, the decrease of this indicator was maximal and statistically significant (–36.8 % against the intact control group, p<0.05). At night, on the contrary, this parameter was slightly different from that in the intact control group (–12.2 %). The total time of immobility of mice on the background of atristamine (100 mg/kg) did not differ from that of the intact control group in the morning. In the daytime, atristamine significantly reduced this indicator (–26.5 %, p<0.05) compared to the intact control. The effect of the test compound on the depressive behavior of mice was decreased in the evening. Animals of this group at night were on average 30 % longer in the state of “behavioral despair” compared to the control. The cosinor analysis showed that the animals of all experimental groups had a 24-hour sinusoidal chronorhythm of depressivity in the tail suspension test. The same type of displacement of acrophases of the depressive behavior parameters in mice relative to physiological values occurs after administration of atristamine and imipramine. Unlike tricyclic antidepressant imipramine, atristamine causes a pronounced daily oscillation of depressive behavior of mice.

Conclusions. Atristamine and imipramine significantly reduced the total time of immobility of animals only in the daytime period (14:00-16:00). The common chronopharmacological feature of the effect of atristamine and imipramine on the depressive behavior of mice is reduction of the antidepressant activities of both substances at night.

Author Biographies

I. M. Podolsky, National University of Pharmacy

Candidate of Pharmacy (Ph.D.), associate professor of the Medicinal Chemistry Department

S. Yu. Shtrygol’, National University of Pharmacy

Doctor of Medicine (Dr. habil.), professor, head of the Department of Pharmacology

V. V. Tsyvunin, National University of Pharmacy

Candidate of Pharmacy (Ph.D.), teaching assistant of the Department of Pharmacology


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Pre-clinical studies of new drugs