ADRENERGIC-RECEPTOR SYSTEMS AND UNSCHEDULED DNA-SYNTHESIS IN THE RAT-BRAIN

Two experiments were carried out in the albino rat to investigate the role of brain adrenergic systems in DNA remodeling. Adult male Sprague -Dawley rats were given an intraventricular microinjection of an adren ergic drug or vehicle followed 2 h later by the intraventricular injec tion of 50 mu Ci of [H-3-methyl]thymidine. The rats were sacrificed 0. 5 h after the injection of the radioactive tracer. The rate of DNA syn thesis was determined by measuring the amount of radioactive precursor incorporated into the DNA extracted from homogenates of several brain areas. In Experiment 1, at time 0 rats received the alpha-adrenergic antagonist phentolamine (5 mu g), the beta antagonist propranolol(10 m u g), the alpha agonist phenylephrine (1 mu g), the beta agonist isopr oterenol (12.5 mu g), or the vehicle. The latter decreased UBDS in neo cortex, and increased it in the septum, neostriatum, hypothalamus, cer ebellum, and rest of the brain. The alpha and beta agonists and antago nists induced several significant effects, depending on the brain regi on. In Experiment 2, rats were bilaterally lesioned in the dorsal nora drenergic bundle (DNB) by injection of 6-hydroxydopamine or were sham lesioned. One week later, at time 0 they were given the alpha agonist phenylephrine (1 mu g), the beta agonist isoproterenol (12.5 mu g), or the vehicle. The DNB-lesioned rats showed a higher UBDS in the hippoc ampus, neocortex, and hypothalamus, which was reversed by the alpha or the beta agonist. The results suggest an influence of the DNB, probab ly as a tonic inhibitor of UBDS in the hippocampus and the hypothalamu s which, in turn, are likely to be mediated by beta- and alpha-adrener gic receptors. In addition, a phasic inhibitory effect seems to be med iated by beta and alpha receptors in the neocortex, and by beta recept ors in the cerebellum. A modulatory role of central adrenergic systems on unscheduled brain DNA synthesis may be inferred from these finding s.