Dynamics of cholinergic synaptic mechanisms in rat hippocampus after stress

Changes in high affinity [ 3 H]choline uptake, newly synthesized [ 3 H]acetylcholine release and [ 3 H]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 (2 h 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 (B max ) was increased to 135% of control only after chronic stress, with no change in K d values. Following chronic stress the changes observed in cholinergic synaptic mechanisms all persists for up to 2 days. Recovery occurred only by the 7th post-stress day. We conclude: (1) 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; (2) 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 (3) 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.