DIFFERENTIAL RELEASE OF ACETYLCHOLINESTERASE IN-VIVO, FROM THE GUINEA-PIG SUBSTANTIA-NIGRA COMPARED TO THE CAUDATE-PUTAMEN FOLLOWING DOPAMINE DEPLETION

In the substantia nigra acetylcholinesterase may have a novel role unr elated to acetylcholine but linked instead to dopamine. Using a sensit ive chemiluminescent system, we have investigated the effects of dopam ine depletion on the in vivo release of acetylcholinesterase in both t he substantia nigra and the caudate putamen. Dopamine levels in the ca udate putamen were significantly depleted compared to the non-lesioned side, using either of two different toxins for dopaminergic nigrostri atal cells: 6-hydroxydopamine (1 or 3 weeks prior to study) or N-methy l-4-phenyl-1,2,5,6-tetrahydropyridine (1 week prior to study). Spontan eous release of acetylcholinesterase from the substantia nigra was sig nificantly reduced following ail three pretreatments; however, in the caudate putamen a significant reduction in the spontaneous release of acetylcholinesterase, compared to controls, was only seen in animals s tudied 1 week after the administration of 6-hydroxydopamine. In all co ntrol groups, application of potassium ions (60 mM) evoked a significa nt release of acetylcholinesterase in the substantia nigra (p < 0.05) and this effect persisted in the surviving neurones following a partia l lesion by neurotoxin pre-treatment. The results from this study are discussed in the light of a regulatory mechanism for acetylcholinester ase release from the striatum, which may come into operation depending on the extent of destruction of dopaminergic nigrostriatal neurones. Copyright (C) 1996 Elsevier Science Ltd.