Effect of stress on norepinephrine-stimulated cyclic AMP formation in brain slices.

Experiments were conducted to determine if stressful procedures, which increase brain norepinephrine (NE) release in rats, lower the responsiveness of central noradrenergic receptors as measured by the catecholamine (CA)-induced cAMP accumulation in hypothalamic and cerebral cortical slices. No conclusive evidence of subsensitivity was found after either acute or chronic electric footshock or continuous restraint. Failure to find a significant reduction after stress may have resulted from several methodological problems. These include (a) the inhibition of phosphodiesterase activity with isobutylmethylxanthine, which may have obscured possible adaptive changes in cAMP degradation and/or adenosine-dependent adrenergic receptors; (b) a low initial responsiveness to NE in these animals as suggested by the greater case in inducing supersensitivity with reserpine than subsensitivity with amphetamine; and (c) the use as a test agent of exogenous NE which may stimulate a far broader population of receptive sites in brain slices than are activated during stress by the local release of endogenous NE.