Research ReportCa2+ modulation in dorsal raphe plays an important role in NREM and REM sleep regulation during pentobarbital hypnosis

Our previous studies indicated that L-type calcium channel blocker diltiazem could potentiate pentobarbital-induced hypnosis through serotonergic system. In view of the important role of dorsal raphe nucleus (DRN) on the sleep regulation and the pharmacological actions of calcium channel blocker, we presumed that Ca2+ in the DRN may play an important role in sleep regulation in pentobarbital treated rats. Therefore, we investigated whether the Ca2+ modulation in DRN by the microinjection of L-type Ca2+ channel antagonist diltiazem, agonist BAY-K-8644, Ca2+ chelator EGTA and CaCl2 would alter the sleep parameters in pentobarbital treated rats. Results showed that perfusion of the agents attenuating Ca2+ function, such as diltiazem (5 or 20 nmol) or EGTA (3 or 6 pmol) into DRN significantly increased pentobarbital (35 mg/kg, i.p.)-induced total sleep (TS), non-rapid eye movement (NREM) sleep and the slow wave sleep (SWS) ratio in NREM sleep. On the contrary, the DRN injection of the agents improving Ca2+ function, such as BAY-K-8644 (10 nmol) or CaCl2 (50 or 100 nmol) significantly reduced pentobarbital (35 mg/kg, i.p.)-induced TS, NREM sleep, rapid eye movement (REM) sleep and REM sleep ratio in TS without influence on SWS. These results suggested that the suppression of Ca2+ function in DRN could increase NREM sleep including SWS, and the elevation of Ca2+ function could reduce both NREM and REM sleep in pentobarbital treated rats.

Graphical abstractDownload high-res image (101KB)Download full-size imageResearch Highlights► Reducing Ca2+ function in rats DRN increase NREM in pentobarbital (PTB) sleep. ► Enhancing Ca2+ function in DRN reduce NREM & REM sleep in PTB treated rats. ► Ca2+ modulation in DRN plays an important role in sleep regulation.