Effects of neurohumoral and adrenergic agents on cyclic amp levels in various areas of the rat brain in vitro

When norepinephrine (NE) at 10^?5 M was added to slices of various areas of the rat brain in vitro there was a 2–5 fold increase in the level of adenosine 3',5'-monophosphate (cyclic AMP) within 6 min in all areas except the cerebellum. The basal level of cyclic AMP in the cerebellum was higher than in other areas of the rat brain, and the response to NE was smaller. Histamine and serotonin (5-HT) at 10^?5 M had no effect on cyclic AMP in any brain area. However, 5-HT when added simultaneously with NE, prevented the rise in cyclic AMP elicited by NE in the hypothalamus, midbrain and brainstem. Pargyline elevated the basal levels of cyclic AMP in all brain areas but did not potentiate the action of NE. Chronic reserpine pretreatment in the rat caused an enhanced cyclic AMP response to NE. No effect on cyclic AMP in any brain area was observed following dopamine, amphetamine, or prostaglandins E₁ and E₂. Theophylline slightly reduced cyclic AMP levels. In slices of rat hypogthalamus NE, epinephrine, isoproterenol and α-methyl NE, significantly elevated cyclic AMP levels. Phenylephrine and several “false” transmitters were without effect. Further studies in the hypothalamus revealed that both α and β adrenergic blocking agents effectively antagonized the cyclic AMP response to NE. These results are somewhat difficult to interpret because the precise cellular location of the observed changes are unknown.