In vitro presynaptic modulation of cholinergic hippocampal activity by pituitary-adrenocortical hormones

In vivo studies have shown that high blood concentrations of pituitary-adrenocortical hormones can activate the hippocampal cholinergic terminals. Incubation of hippocampal synaptosomal preparations with methylprednisolone, or with ACTH at concentrations comparable to stress-induced high concentrations in plasma, did not have any significant effects on the cholinergic parameters measured under unactivated conditions. In the presence of either high K⁺ or of ACh, choline uptake was decreased. This decrease was not affected by methylprednisolone. However, methyl-prednisolone did enhance ACh release both after a previous increase (induced by K⁺) or a decrease (induced by ACh) of ACh release. In contrast, ACTH had no direct effects on either unactivated or K⁺-stimulated synaptosomes. Thus, a differential effect was exerted by methylprednisolone on the two presynaptic regulatory mechanisms: choline uptake (no change) and ACh release (increase). We suggest that the activation, observed in vivo, resulted mainly from indirect action of the hormones on the hippocampal cholinergic terminals, in view of the fact that the direct effect in vitro was partial.