Differential Release of Acetylcholinesterase in vivo, from the Guinea Pig Substantia Nigra Compared to the Caudate Putamen Following Dopamine Depletion

Abstract

In the substantia nigra acetylcholinesterase may have a novel role unrelated to acetylcholine but linked instead to dopamine. Using a sensitive chemiluminescent system, we have investigated the effects of dopamine depletion on the in vivo release of acetylcholinesterase in both the substantia nigra and the caudate putamen. Dopamine levels in the caudate putamen were significantly depleted compared to the non-lesioned side, using either of two different toxins for dopaminergic nigrostriatal cells: 6-hydroxydopamine (1 or 3 weeks prior to study) or N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (1 week prior to study). Spontaneous release of acetylcholinesterase from the substantia nigra was significantly reduced following all three pretreatments; however, in the caudate putamen a significant reduction in the spontaneous release of acetylcholinesterase, compared to controls, was only seen in animals studied 1 week after the administration of 6-hydroxydopamine. In all control groups, application of potassium ions (60 mM) evoked a significant release of acetylcholinesterase in the substantia nigra ( p < 0.05) and this effect persisted in the surviving neurones following a partial lesion by neurotoxin pre-treatment. The results from this study are discussed in the light of a regulatory mechanism for acetylcholinesterase release from the striatum, which may come into operation depending on the extent of destruction of dopaminergic nigrostriatal neurones. Copyright © 1996 Elsevier Science Ltd.