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Sorensen E, Gronli J, Bjorvatn B, Ursin R: The selective 5-HT (1A) receptor antagonist p-MPPI antagonizes sleep--waking and behavioural effects of 8-OH-DPAT in rats. Behav Brain Res. 2001 Jun;121(1-2):181-7.
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-pipera zine (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. |
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