Mechanism of stress-induced subsensitivity to norepinephrine.

Chronic footshock stress in rats produces a persistent reaction in the sensitivity of the norepinephrine (NE)-cAMP generating system in the cerebral cortex, an effect similar to that reported after chronic antidepressant treatment. The present studies show that footshock-induced subsensitivity is not related to changes in either beta or alpha-1 adrenergic receptors, phosphodiesterase or total adenylate cyclase activity. The stress does not induce a small, selective decrease in binding at high affinity alpha-2 receptor sites but this change does not appear to explain the decreased responsiveness to NE. These data and related findings by others using restraint stress indicate that the mechanism of subsensitivity after chronic stress resembles in part that seen after antidepressants but may also involve additional phenomena which may not occur after the latter agents.