AN ATTENUATED ALPHA-1 POTENTIATION OF BETA-ADRENOCEPTOR-STIMULATED CYCLIC-AMP FORMATION AFTER REPEATED SALINE INJECTIONS IN FISCHER-344 STRAIN RATS

We investigated the behavioral and neurochemical features of Fischer 3 44 strain rats in which a depressive state was induced by repeated han dling and saline injections as a mild stressor. The repeated intraperi toneal injections of saline (2 ml/kg, twice a day for 14 days) elicite d 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 exposur e 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-stimulate d cAMP formation between the control and the stress groups was totally abolished. Phenylephrine enhanced isoproterenol-stimulated cAMP forma tion in the control but not in the stress group. From these results, i t is postulated that the alpha-1 potentiation of beta adrenoceptor-sti mulated cAMP formation was attenuated in the stress group. These findi ngs suggest that the manipulation of mild stressor with repeated handl ing and saline injections to Fischer 344 rats elicits a depressive sta te 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.