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Modulation of sleep and waking states by D-1 receptors

Research Laboratories, Schering-Plough S.p.A., I-20060 Comazzo, Milan, Italy

Maria Trampus

Research Laboratories, Schering-Plough S.p.A., I-20060 Comazzo, Milan, Italy

This review describes pharmacological studies showing that the dopamine D-1 receptor subtype is involved in the modulation of states of sleep and wakefulness. Stimulation of D-1 receptors by SKF 38393 produces electro encephalographic (EEG) arousal, enhances duration of wakefulness and markedly reduces the stage of rapid eye movement sleep (REM). Importantly, all these effects occur in the absence of the most typical dopamine- mediated behaviours such as stereotyped movements or hyperactivity. On the contrary, studies with the selective D-1 receptor antagonists, especially with the drug SCH 23390, have shown that these compounds increase duration of total sleep including both components, non-REM and REM. Likewise, they produce sedation in different animal species. An important distinguishing feature of the action of D-1 antagonists, compared with non-selective or D-2-selective antagonists, is their ability to enhance the amount of REM. The effect appears to be specifically mediated by D-1 receptors, whereas the interaction of SCH 23390 or its derivatives with the serotonin receptor subtype 5-HT₂ may contribute to an increase of total sleep, but does not seem to influence REM changes. The overall findings indicate that D-1 receptors are involved in mediating the sedation-arousal continuum and the states of sleep-wakefulness. The REM-enhancing action of D-1 antagonists appears to be a unique response, which, considering that sleep disorder is a prominent feature in psychiatric illness, may have clinical relevance. The involvement of D-1 receptors in the modulation of REM stimulates further research aimed at gaining insights into both the complex process of sleep and the function of the D-1 receptor within the central nervous system.

Key Words: neuroleptics • dopamine receptors • D-1 antagonists • D-2 antagonists • sleep stages • REM sleep

Journal of Psychopharmacology, Vol. 6, No. 1, 61-67 (1992)
DOI: 10.1177/026988119200600112


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