Acetylcholinesterase inhibitors block acetylcholine-evoked release of dopamine in rat striatum, in vivo.

In the rat striatum, acetylcholine (ACh) increases dopamine (DA) release. The role of increased cholinergic activity provoked by acetylcholinesterase inhibitors (AChEi) on DA release is currently under revision after recent papers have shown a blockade of nicotinic transmission by AChEi in vitro. To study the effects of AChEi in vivo, Fasciculin2 (FAS), a peptidergic AChEi, and physostigmine (PHY), a classical carbamate AChEi, were applied through push-pull or microdialysis cannulae respectively, to the striatum of rats, alone or with ACh. Extracellular concentrations of DA were assessed by HPLC with electrochemical detection. Alone, the AChEi studied did not provoke changes in basal extracellular levels of DA, in the different doses studied. ACh (100 microM, 1 and 5 mM) applied through the push-pull cannulae in basal conditions provoked a dose-dependent increase of extracellular DA. This effect was not observed with ACh in concentrations of 100 microM and 1 mM if FAS (0.4 and 4.2 microM) was applied first. Higher concentrations of ACh (5 mM) evoked a partial response after FAS 0.42 microM, an effect still blocked by FAS at 4.2 microM. PHY 50 microM applied through microdialysis completely blocked the increase in DA release provoked by ACh 10, 20 mM, while at ACh 30 mM, PHY 50 microM only partially blocked the evoked increase. A partial blockade was also observed with PHY 20 microM, on the three different concentrations of ACh. On the other hand PHY 10 microM did not block any of the ACh doses perfused. These results showed that AChEi like FAS and PHY interfere with the ACh-evoked DA release in the striatum.