Chronobiological aspects of the anti-stress effect of anxiolytics

BACKGROUND: A stressful event, being a disturbing factor, is invariably accompanied by the disorganization of biological rhythms.

AIM: To examine the effects of stress and pharmacological substances on two models of the temporal organization of behavior, i.e., circadian locomotion and swimming dynamics in rats.

MATERIALS AND METHODS: The daily dynamics of rat mobility were assessed in a specially designed device consisting of living cells connected to a computer. Each cell is connected by a lever and a hinge with a button. When the rat moved from one end of the box to the other, the contact was closed, and the program autonomously summed up the number of such movements for each hour of the experiment. The total number of transitions was counted in 3 h, followed by the construction of a chronogram of the circadian rhythm of mobility. To assess the effect of substances on the circadian rhythm, anxiolytics diazepam (0.1 mg/kg), tofisopam (10 mg/kg), and epiphyseal hormone melatonin (0.1 mg/kg) were injected intraperitoneally into rats. Rats that received the same volume of saline injections (0.5 mL) served as controls.

RESULTS: Substances with anxiolytic properties, benzodiazepine derivatives diazepam (0.1 mg/kg) and tofisopam (10 mg/kg), and epiphyseal hormone melatonin (0.1 mg/kg), similarly eliminated stress-induced dysrhythmia in rats. Under their influence, the circadian rhythm of motor activity was normalized, and adaptive shifts were observed in the temporal dynamics of forced swimming.

CONCLUSION: A single stressful event disrupts the dynamics of daily mobility in rats. Diazepam, tofisopam, and melatonin, while differing in potency, generally alleviate these disorders. In particular, anxiolytics restore the rhythm in animals highly sensitive to stress. The studied substances reorganized the temporal dynamics in rats subjected to forced swimming and increased the proportion of long-period oscillations. Primary or secondary elimination of stress dysrhythmia is an important factor in the specific action of anxiolytics.