The Neuropharmacology of Serotonin and Sleep: an Evaluation
Depression is often associated with disruption of the normal sleep cycle. In particular, though patients frequently show disturbances in sleep continuity and a reduction in slow wave sleep, the most commonly observed effects are a shortened latency to the first episode of rapid eye movement (REM) sleep after sleep onset (i.e., a reduced REM latency), and an increase in REM density in the first REM periods during the night (Kupfer, 1982). The administration of antidepressant drugs typically suppresses most measures of REM sleep (see Kupfer, 1982), and it is an issue of general interest whether there is a connection between the pharmacologies of REM suppression and of antidepressant treatment. Several of the antidepressants in past, current, and experimental use are active at serotonin (5HT) synapses. The antidepressant action of such drugs is commonly thought to be associated with their ability to enhance transmission across 5HT synapses (see Willner, 1985). If this is the case and if there is a connection between a drug’s effects on sleep and depression, then these agents should have predictable actions on sleep, as should other drugs that affect 5HT synaptic function. The purpose of this review is to evaluate this latter proposition. To this end, a discussion is presented of the effects that each of several classes of agents that modify 5HT transmission has on sleep in mammals. These are broadly classed as agents that decrease or increase synaptic transmission.
KeywordsNREM Sleep NREM Sleep Time Cortical Slow Wave
Unable to display preview. Download preview PDF.
- Aghajanian GK, Wang RY (1978): Physiology and pharmacology of central serotonergic neurons. In: Psychopharmacology: A Generation of Progress, Lipton MA, DiMascio A, Killam KF, eds. New York: Raven Press, pp. 171–183Google Scholar
- Bjorklund A, Baumgarten HG, Nobin A (1974): Chemical lesioning of central monoamine axons by means of 5,6-dihydroxytryptamine and 5,7-dihydroxytryptamine. In: Advances in Biochemical Psychopharmacology, Volume 10, Costa E, Gessa GL, Sandler M, eds. New York: Raven Press, pp. 13–33Google Scholar
- Fornai C, Radulovacki M (1983a): Sleep suppressant action of fenfluramine in rats. I. Relation to postsynaptic serotonergic stimulation. J Pharmacol Exp Ther 225:667–674Google Scholar
- Fornai C, Radulovacki M (1983b): Sleep suppressant action of fenfluramine in rats. H. Evidence against the involvement of presynaptic serotonergic mechanism. J Pharmacol Exp Ther 225:675–681Google Scholar
- Fuxe K, Kiianmaa K (1978): 5-hydroxytryptamine neurons and the sleepwakefulness cycle. Effects of metergoline and zimelidine. Neurosci Lett 8:55–58Google Scholar
- Koe BK, Weissman A (1966): p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther 154:499–516Google Scholar
- Lipton MA, Gordon R, Guroff G, Udenfriend S (1967): p-Chlorophenylalanineinduced chemical manifestations of phenylketonuria in rats. Science 156:248–250Google Scholar
- Lovenberg W, Jequier E, Sjoerdsma A (1968): Tryptophan hydroxylation in mammalian systems. In: Advances in Pharmacology, volume 6A, Garattini S, Shore PA, eds. New York: Academic Press, pp. 21–36Google Scholar
- McCarley RW (1980): Mechanisms and models of behavioral state control. In: The Reticular Formation Revisited, Hobson JA, Brazier MAB, eds. New York: Raven Press, pp. 375–403Google Scholar
- Pujol JF, Keane P, Bobillier P, Renaud B, Jouvet M (1978): 5,6-dihydroxytryptamine as a tool for studying sleep mechanisms and interactions between monoaminergic systems. Ann NY Acad Sci 305:576–589Google Scholar
- Rechtschaffen A, Lovell RA, Freedman DX, Whitehead WE, Aldrich M (1973): The effect of parachlorophenylalanine on sleep in the rat: some implications for the serotonin-sleep hypothesis. In: Serotonin and Behavior, Barchas J, Usdin E, eds. New York, Academic PressGoogle Scholar
- Sallanon M, Buda C, Janin M, Jouvet M (1982): 5-HT antagonists suppress sleep and delay its restoration after 5-HTP in p-chlorophenylalanine-pretreated cats. Eur J Pharmacol 82:29–35Google Scholar