Sleep/waking effects of a selective 5-HT(1A) receptor agonist given systemically as well as perfused in the dorsal raphe nucleus in rats

Abstract

Sleep/waking stages and behavior were studied following the selective 5-HT(1A) agonist 8-OH-DPAT given subcutaneously (s.c.) (0.010-0.375 mg/kg) as well as perfused continuously (10 μM) for 6 h into the dorsal raphe nucleus (DRN) using microdialysis. Given systemically, 8-OH-DPAT at 0.375 mg/kg s.c. induced 5-HT behavioral syndrome, increased waking to 149% and reduced slow wave sleep (SWS) to 86%, transition to 76% and rapid eye movement (REM) sleep to 73%. The effect on deep SWS (SWS-2) was biphasic, with an increase after 2 h. 8-OH-DPAT at 0.010 mg/kg did not have any vigilance effects. 8-OH-DPAT perfusion in DRN produced a fourfold increase in REM sleep compared to perfusion of artificial cerebrospinal fluid. This is consistent with the hypothesis that reduced 5-HT neurotransmission following 5-HT(1A) autoreceptor stimulation will disinhibit cholinergic REM- promoting mesopontine neurons and thereby lead to a REM sleep increase. The other sleep/waking stages were not significantly affected by 8-OH-DPAT perfusion in DRN.