TACRINE INCREASES STIMULATION-EVOKED ACETYLCHOLINE-RELEASE FROM RAT HIPPOCAMPAL SLICES

We examined the effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine) on endogenous acetylcholine (ACh) release from rat hippocampal slices. Tacrine (more than 1 mu M) increased the measurable amount of basal ACh release. On the other hand, in the presence of physostigmine (50 mu M; under this condition, cholinesterase activity was inhibited), tacrine did not enhance the basal ACh release. Tacrine at more than 100 mu M increased the submaximal electrical stimulation-evoked release of ACh in both the absence and presence of physostigmine (50 mu M). This effect of tacrine was abolished by a combination of atropine (100 nM) and physostigmine. These results indicate that a high-dose of tacrine increases cholinergic neurotransmission not only by inhibition of cholinesterase but also by increasing ACh release through an atropine-like effect, perhaps by blockade of part of the process of muscarinic autoinhibition.