230 NEURONAL NETWORK CHANGES ON PASSING TO SLEEP AFTER WAKEFULNESS

Abstract

Aims: To study the effect of MCHmicroinjections and MCH immunoneutralization into the DR on sleep parameters as well as on the forced swim test (FST), a behavioral approach commonly used to test antidepressive drugs. Methods: Sleep studieswere performed in adult rats (n=12) that were chronically implanted for polysomnographic recordings. A guide cannula directed toward the DR was also implanted for microinjections of MCH and anti-MCH antibodies. Six-hour recordings were performed during the light phase of the light/dark cycle, and analysis of sleep parameters was carried out afterwards. Standard FST and the open field test (OFT) were performed in another group of rats (n=12) that were implantedwith only a guide cannula directed toward the DR. Five days after, the behavioral effects of MCH and MCH antibodies microinjected into the DR were analyzed in both paradigms. Results: MCH injection (100 ng) resulted in a moderate increase of slow wave sleep and a marked increase of REM sleep (35.5±2.5 vs. 20.8±3.4 minutes, p<0.01) compared with vehicle microinjections. This effect was due to an increase in the number of REM sleep episodes. Moreover, the immunoneutralization ofMCH (anti-MCH antibodies 1:100) decreased the REM sleep time to less than 50% of the control values, as determined by a decrease in the number of REM sleep episodes. In the behavioral tests, while MCH (50 ng) microinjected into the DR increased the immobility time in the FST (p<0.01; depressive-like response), anti-MCH antibodies (1:500) decreased the time to 56% of the control values (p<0.05; antidepressant-like effects). These effects were specific to the FST because these patterns of motor activities were not reproduced in the OFT. Conclusions: These data strongly suggest that theMCHergic system, through the modulation of DR neurons, promotes REM sleep. In addition, the neuropeptide is likely involved in mood regulation. Support: Supported by PDT-Salud 76/36 grant