Non-cholinergic action of exogenous acetylcholinesterase in the rat substantia nigra. I. Differential effects on motor behaviour.

In the substantia nigra a non-cholinergic action of acetylcholinesterase has been demonstrated on motor behaviour. At the cellular level, electrophysiological studies have shown not only excitatory actions of AChE, but also inhibitory effects in response to larger amounts of the protein. In this study the possible dose-dependent effects of AChE were therefore explored in relation to circling behaviour. Both 'ipsiversive' turning (towards side of infusion and indicative of net decreased activity in the nigrostriatal pathway) and 'contraversive' turning (away from side of infusion and indicative of net increased activity) was observed for at least 2 weeks following a single unilateral AChE infusion. Ipsiversive turning occurred in 15-20% of animals in each group irrespective of dose. However, the actual number of animals exhibiting contraversive turning increased with increasing dose, whilst those not responding decreased. The most critical factor for direction of response appeared to be related not to dose, but cannula placement; infusion of AChE into more posterior regions of the substantia nigra evoked contraversive circling, whereas there appeared to be a discrete site in the anterior nigra in which AChE induced ipsiversive turning. This study thus suggests that subpopulations of nigrostriatal neurons show differential responsiveness to AChE.