An attenuated alpha-1 potentiation of beta adrenoceptor-stimulated cyclic AMP formation after repeated saline injections in fischer 344 strain rats

Abstract

We investigated the behavioral and neurochemical features of Fischer 344 strain rats in which a depressive state was induced by repeated handling and saline injections as a mild Stressor. The repeated intraperitoneal injections of saline (2 ml/kg, twice a day for 14 days) elicited a moderate suppression of body weight gain, a decrease in their open field activity and a prolonged immobility in the tail suspension test. In the stress-exposed rats, the tissue content of norepinephrine (NE) was increased in the cerebral cortex and hypothalamus, whereas that of dopamine or serotonin was not affected. Although the stress exposure did not affect the binding properties of either the alpha-1 or beta adrenoceptors, it suppressed cAMP formation stimulated by NE, but not by isoproterenol or forskolin, in the cerebral cortical slices. In the presence of prazosin or phorbol ester, the difference in NE-stimulated cAMP formation between the control and the stress groups was totally abolished. Phenylephrine enhanced isoproterenol-stimulated cAMP formation in the control but not in the stress group. From these results, it is postulated that the alpha-1 potentiation of beta adrenoceptor-stimulated cAMP formation was attenuated in the stress group. These findings suggest that the manipulation of mild Stressor with repeated handling and saline injections to Fischer 344 rats elicits a depressive state characterized by the behavioral changes and the attenuated alpha-1 potentiation in the cerebral cortex, and that this manipulation might be available for the study of the stress-induced depressive state as a generally acceptable mild stress model.