Aims: 

Human preclinical studies showed that the early anxiogenic effect of the selective serotonin reuptake inhibitor (SSRI) antidepressants is probably mediated by 5-HT_2C receptors. The development of antidepressant effects and the cessation of the anxiety-like side effects are caused by adaptive changes in the receptor function, which take several weeks to develop. The wake promoting effect of 5-HT_2C antagonists, as well as the adaptive changes in anxiogenic effect of SSRIs following chronic administration have already been published. However, studies on the effects of chronic SSRI treatment on the functions of 5-HT_2C receptors related to wakefulness and motor activity are absent. As wake promoting and anxiogenic effects usually do not appear together, we presume that the adaptive changes of 5-HT_2C receptors, which are responsible for wake and motor activity, are different from the anxiolytic effects.

Methods: 

We studied the changes of the time spent in wake on the second (acute) and on the 21^st (chronic) days after the implantation of an osmotic pump filling with escitalopram (10 mg/kg/day) using electroencephalograph in male Wistar rats. On both days, a single dose of a selective 5-HT_2C antagonist (SB-242084, 1 mg/kg) or saline were injected intraperitoneally. Total wake was analyzed in the first hour after light onset, and was divided into active and passive wake by motility.

Results: 

The acutely administered SB-242084 increased the time spent in total wake compared to the acute saline, irrespectively of the escitalopram treatment, both on the second and the 21^st days. On the first day, this change was caused by the increased time spent in active wake, while on the second time point, the significant increase in passive wake led to the enhancement in total wake.

Conclusion: 

The wake promoting effect of 5-HT_2C receptor antagonist was invariable, while its effect on motor activity decreased following chronic SSRI treatment.