The selective 5-HT(1A) receptor antagonist p-MPPI antagonizes sleep--waking and behavioural effects of 8-OH-DPAT in rats.
Systemic administration of the selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) increases waking and reduces slow wave sleep (SWS) and rapid eye movement (REM) sleep in the freely moving rat. The selective 5-HT(1A) antagonist 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl-piperazine (p-MPPI) induces a dose-related decrease in REM sleep. The present study examined p-MPPI's potential as an antagonist of the sleep and waking responses elicited by 8-OH-DPAT. Also, the experiments explored the ability of p-MPPI to block behavioural reactions of the 5-HT syndrome induced by 8-OH-DPAT, and whether p-MPPI induced any behavioural effects of its own. This study demonstrated that pre-treatment with p-MPPI (5 mg/kg intraperitoneal (i.p.)) 30 min before 8-OH-DPAT (0.375 mg/kg subcutaneously (s.c.)) reduced the effect of 8-OH-DPAT on waking and REM sleep. Also, p-MPPI (5 and 10 mg/kg i.p.) reduced the effect of 8-OH-DPAT on locomotion and partially or completely antagonized hindlimb abduction and flat body posture. No overt behavioural change was produced by p-MPPI alone. Thus, p-MPPI behaved as a true 5-HT(1A) antagonist.
Sørensen
E
E
Department of Physiology, University of Bergen, Arstadveien 19, N-5009 Bergen, Norway. eli.soerensen@fys.uib.no
Grønli
J
J
Bjorvatn
B
B
Ursin
R
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; 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*; D012894:Sleep Stages / 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; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin