6-Hydroxydopamine-induced turning behaviour in the rat: the significance of acetylcholinesterase in cerebrospinal fluid.

In the substantia nigra, acetylcholinesterase may have a novel function related not to cholinergic transmission, but to the homeostasis of dopaminergic nigrostriatal neurones. The initial aim of this study was thus to see whether, in the rat, release of the enzyme into cerebrospinal fluid would reflect turning behaviour following unilateral 6-hydroxydopamine lesions of varying severity. It was found that acetylcholinesterase levels, lower than those in the cerebrospinal fluid of control rats, were accompanied by marginal circling behaviour and a small loss of striatal dopamine: on the other hand, elevated acetylcholinesterase activity was observed in the cerebrospinal fluid of rats displaying vigorous turning behaviour and with large depletion of striatal dopamine. It has already been demonstrated that exogenous acetylcholinesterase, applied locally to nigral neurones, has both electrophysiological and behavioural effects reminiscent of dopamine agonists. Hence it is possible that exogenous acetylcholinesterase could modify turning behaviour resulting from unilateral striatal dopamine depletion. Purified acetylcholinesterase, administered by cisternal puncture, attenuated circling behaviour for up to 7 days. The possible mechanisms are discussed by which endogenous acetylcholinesterase in cerebrospinal fluid could serve as an index of dopamine depletion in the nigrostriatal pathway and how exogenous enzymes might alleviate the accompanying motor dysfunction.