Dynamics of cholinergic synaptic mechanisms in rat hippocampus after stress

Abstract

Changes in high affinity [3H]choline uptake, newly synthesized [3H]acetylcholine release and [3H]quinuclidinylbenzilate (QNB) binding were characterized in crude synaptosomal preparations from rat hippocampus immediately after different intervals of immobilization stress and at different times following chronic intermittent stress (2h once daily for 5 days). Choline uptake was increased to 125% of unhandled controls after 10 min of stress, after 2 h it returned to control levels and after chronic stress uptake was reduced to 75% of control. Acetylcholine release was enhanced after all stress intervals. Maximal muscarinic (QNB) binding capacity (Bmax) was increased to 135% of control only after chronic stress, with no change in Kd values. Following chronic stress the changes observed in cholinergic synaptic mechanisms all persist for up to 2 days. Recovery occurred only by the 7th post-stress day. We conclude: presynaptic hippocampal cholinergic terminals are rapidly activated by stressful stimuli and this is expressed by an increase in choline uptake and newly synthesized acetylcholine release; after prolonged periods of stress adaptive changes in the cholinergic terminals are expressed by a reduction in choline uptake and an elevation in the number of muscarinic binding sites; and the chronic stress-induced changes are slow to recover. The results demonstrate that the septo-hippocampal cholinergic system is an integral part of the adaptive response to stress.