Dopamine autoreceptor antagonists: effects on sleep-wake activity in the rat.

The effects of the putative dopamine (DA) autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, and cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, on sleep-wake activity, EEG, and motor activity in the rat were studied. Both drugs induced a dose-dependent increase in wakefulness (W) and a reduction in non-REM sleep (NREMS). A definite tendency to a suppression of REM sleep (REMS) could also be observed. The results of spectral analysis indicated that EEG slow wave activity, a marker of sleep intensity, was particularly sensitive to the drugs. Slight differences between the two drugs were observed: (+)-AJ 76 seemed to be more efficacious than (+)-UH 232 in stimulating motor activity. (+)-UH 232 tended to suppress slow wave activity more strongly than (+)-AJ 76. It is suggested that the increase in W following administration of (+)-AJ 76 resulted predominantly from locomotor activation, while (+)-UH 232 might also act on dopaminergic mechanisms involved in the regulation of sleep.