Regulation of sleep after neonatal locus coeruleus lesion: functional evidence of beta-adrenergic supersensitivity.

In the present report we analyzed the long-term effect of neonatal noradrenergic denervation on the regulation of paradoxical sleep in the rat. The locus coeruleus was destroyed bilaterally at 4 days of age by direct infusion of 6-hydroxydopamine into the nuclei. After they reached adulthood, the rats received either i.p. injections of a beta-blocker, propranolol, or the same treatment combined with intraventricular infusion of a beta-agonist, isoproterenol. Several doses of each drug were tested. The effects of propranolol, alone and together with isoproterenol, on paradoxical sleep (a decrease for the former drug and a restoration for the latter combination) were significantly more pronounced in the lesioned group than in age-paired controls. These data illustrate a functional aspect of the denervation supersensitivity phenomenon in beta-receptors.