Reduction of the cyclic adenosine 3',5'-monophosphate response to catecholamines in rat brain slices after repeated restraint stress.

Restraint stress reduces the cyclic AMP (cAMP) response to norepinephrine (NE) in slices of the rat cerebral cortex and hypothalamus. This effect is found after repeated but not single exposure to stress and persists for at least 24 hr poststress. The magnitude of the reduction is dose-dependent in that greater decreases are found after higher frequencies and longer durations of restraint as well as after more disturbance during the stress. Analysis of the NE-cAMP dose-response curve indicates that the stress reduces the maximum cAMP response to NE but does not increase the EC50 value of NE. The cAMP response to isoproterenol is only slightly affected by the stress. No effect is observed on specific [3H]dihydroalprenolol binding in either brain region at 24 hr poststress. These results suggest that repeated restraint stress produces a selective persistent reduction of the function of brain non-beta adrenergic receptors. This effect may be mediated by an increased release of adrenocorticotropic hormone as chronic infusion of the latter hormone mimics the action of stress on cAMP responses to catecholamines. An increased release of brain NE may also be involved as repeated administration of the NE-reuptake inhibiting antidepressant, desmethylimipamine, reduces the function of non-beta as well as beta adrenergic receptors as evidenced by reductions of both the NE- and isoproterenol-cAMP responses.