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Abstract

Sleep suppressant action of fenfluramine in rats. II. Evidence against the involvement of presynaptic serotonergic mechanism.

C Fornal and M Radulovacki
Journal of Pharmacology and Experimental Therapeutics June 1983, 225 (3) 675-681;
C Fornal
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Abstract

The present study investigated the involvement of presynaptic serotonergic mechanisms in the sleep suppressant action of fenfluramine, an indirect serotonin (5-HT) receptor agonist. Rats implanted with cerebrocortical and dorsal neck muscle electrodes were pretreated with either fluoxetine, an inhibitor of 5-HT uptake, or p-chlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis. Animals were continuously monitored by the EEG for 12 hr after an i.p. injection of 5 mg/kg of dl-fenfluramine hydrochloride. Pretreatment with fluoxetine failed to antagonize the fenfluramine-induced suppression of slow-wave sleep and rapid-eye-movement sleep. However, chemical analyses showed that fluoxetine pretreatment completely prevented the depletion of brain 5-HT produced by fenfluramine, suggesting that fenfluramine did not gain entry into serotonergic neurons. Depletion of brain 5-HT by PCPA also failed to antagonize the sleep suppression caused by fenfluramine as well as that observed after administration of quipazine, a direct 5-HT receptor stimulant. Because administration of fenfluramine to PCPA-pretreated rats produced no additional depletion of 5-HT, it appears that 5-HT was no longer available for release by fenfluramine in these animals. Furthermore, neither pretreatment with fluoxetine nor PCPA antagonized the head-shaking induced by fenfluramine, a behavior associated with activation of central 5-HT receptors. These data indicate that the suppression of sleep produced by fenfluramine is not mediated through release of 5-HT as brain 5-HT concentrations were not related to the behavioral effects of the drug. The sleep suppressant action of fenfluramine may therefore result from a direct action of the drug on postsynaptic 5-HT receptors.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 225, Issue 3
1 Jun 1983
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Abstract

Sleep suppressant action of fenfluramine in rats. II. Evidence against the involvement of presynaptic serotonergic mechanism.

C Fornal and M Radulovacki
Journal of Pharmacology and Experimental Therapeutics June 1, 1983, 225 (3) 675-681;

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Abstract

Sleep suppressant action of fenfluramine in rats. II. Evidence against the involvement of presynaptic serotonergic mechanism.

C Fornal and M Radulovacki
Journal of Pharmacology and Experimental Therapeutics June 1, 1983, 225 (3) 675-681;
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