Adrenocortical Steroids Modify Neurotransmitter‐Stimulated Cyclic AMP Accumulation in the Hippocampus and Limbic Brain of the Rat

Abstract: Glucocorticoid hormones are known to affect limbic system structures that have high levels of specific receptors for glucocorticoids, especially the hippocampus (HIPP). To understand how glucocorticoids may affect syn‐aptic transmission, we have tested the effects of adrenal removal and glucocorticoid replacement on neurotransmit‐ter‐stimulated cyclic AMP accumulation in brain slices from the rat limbic system. Adrenalectomy (ADX) caused an enhancement of vasoactive intestinal peptide (VIP)‐stimulated cyclic AMP accumulation in HIPP, amygdala (AMYG), and septum (SEP). In HIPP, ADX increased the cyclic AMP response to isoproterenol (ISOP) and decreased the response to histamine (HIST). In the AMYG and SEP, ADX did not affect significantly the action of ISOP, but ADX did decrease the response to HIST in AMYG. Administration of dexamethasone or corticosterone reversed the effects of ADX on cyclic AMP accumulation in the HIPP. The dexamethasone action on VIP‐stimulated cyclic AMP accumulation takes place within 48 h and is most apparent in the mid‐range of the VIP dose‐response curve. These results demonstrate that glucocorticoids regulate neurotrans‐mitter‐stimulated cyclic AMP generation in a fashion that is specific, both for the neurotransmitter involved and for the brain regions affected.