Sleep-wake effects following the selective 5-HT(1A) receptor antagonist p-MPPI in the freely moving rat.
The 5-HT(1A) receptors appear to play an important role in the serotonergic modulation of sleep and waking. Both presynaptic somatodendritic 5-HT(1A) autoreceptors and postsynaptic 5-HT(1A) heteroreceptors may be involved. The present study addressed the question of whether the selective 5-HT(1A) receptor antagonist 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethy l-p iperazine (p-MPPI) affected sleep and waking and whether such an effect would be dose-related. Polygraphic recording of sleep and waking in freely moving rats was employed following control injection and three doses of p-MPPI (1, 5 and 10 mg/kg i.p. in a balanced order design. Waking was increased and deep slow wave sleep decreased, while rapid eye movement (REM) sleep was suppressed over the first 6 h following injection, compared to after control injection. REM sleep was also suppressed following 10 mg/kg i.p. of p-MPPI as compared to following 1 mg/kg i.p. of p-MPPI. The interpretation of the effects is complex and the effects are not easily compatible with a simple model for serotonergic sleep-waking modulation. However, the REM sleep reduction probably reflects p-MPPIs ability to block the presynaptic 5-HT(1A) autoreceptors, increasing the firing activity in the serotonergic neurones and possibly inhibiting serotonin sensitive REM sleep active neurones.
Sørensen
E
E
Department of Physiology, University of Bergen, Arstadveien 19, N-5009, Bergen, Norway. eli.soerensen@pki.uib.no
Bjorvatn
B
B
Ursin
R
R
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
D000631:Aminopyridines; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine