Comparison of the behavioural effects of infusion of carbachol and acetylcholinesterase into the rat substantia nigra.

It has been postulated for many years that acetylcholinesterase (AChE) may play a nonclassical role in the substantia nigra, unrelated to its ability to hydrolyse acetylcholine. In this study the behavioural effects of unilateral infusion of AChE and a cholinergic agonist, carbachol, were compared. Carbachol induced ipsiversive circling over a very short time scale (minutes), whereas AChE induced contraversive circling, but over a longer time course-10 days. Both agents showed selectivity of response within the substantia nigra: acetylcholinesterase was only effective when infused into the most rostral region of the substantia nigra and its effects were limited to the pars compacta. In contrast, carbachol had effects in both the pars compacta and reticulata, with a graded sensitivity to carbachol in the rostral/caudal plane; infusions into rostral regions induced high rates of circling compared to more caudal areas, suggesting that the cholinergic input to the substantia nigra is not homogenous, but greater in rostral regions. This disparity between the effects of carbachol and AChE would, therefore, suggest that AChE is not exerting its long-term behavioural actions via a cholinergic mechanism, both in terms of time course of the response and the areas within the substantia nigra sensitive to these agents.