In vitro evidence for increased facilitation of striatal acetylcholine release via pre- and postsynaptic NMDA receptors in hemiparkinsonian rats

The NMDA-evoked acetylcholine release from striatal slices and synaptosomes was investigated in rats subjected to unilateral injection of g-hydroxydop amine into the substantia nigra. In slices prepared from the striatum contr alateral to the lesion, the NMDA-evoked endogenous acetylcholine release wa s not significant at 10 mu M NMDA and maximal at 100 mu M NMDA (124 +/- 19% ). Conversely, in slices taken from the dopamine-depleted striatum, NMDA wa s effective even at 10 mu M (41 +/- 4%), and at 100 mu M (196 +/- 24%) effi cacy was nearly doubted. In synaptosomes prepared from the contralateral st riatum, NMDA maximally stimulated 20 mM KCl-induced endogenous acetylcholin e release at 1 mu M (66 +/- 5.1%), with lower concentrations (0.01-0.1 mu M ) being ineffective. Conversely, in synaptosomes prepared from the dopamine -depleted striatum, NMDA maximally enhanced the K+-evoked acetylcholine rel ease at 0.1 mu M(118 +/- 12.4%). Concentration-response curves of NMDA-evok ed acetylcholine release in sham-operated rats could be superimposed on tho se observed in the contralateral striatum of the 6-hydroxydopamine-lesioned animals. The present data support the view of an increased glutamatergic r egulation of striatal acetylcholine release via pre- and post-synaptic NMDA receptors during Parkinson's disease.