The NMDA-evoked acetylcholine release from striatal slices and synaptosomes was investigated in rats subjected to unilateral injection of 6- hydroxydopamine into the substantia nigra. In slices prepared from the striatum contralateral to the lesion, the NMDA-evoked endogenous acetylcholine release was not significant at 10 μM NMDA and maximal at 100 μM NMDA (124 ± 19%). Conversely, in slices taken from the dopamine-depleted striatum, NMDA was effective even at 10 μM (41 ± 4%), and at 100 μM (196 ± 24%) efficacy was nearly doubled. In synaptosomes prepared from the contralateral striatum, NMDA maximally stimulated 20 mM KCl-induced endogenous acetylcholine release at 1 μM (66 ± 5.1%), with lower concentrations (0.01-0.1 μM) being ineffective. Conversely, in synaptosomes prepared from the dopamine-depleted striatum, NMDA maximally enhanced the K+-evoked acetylcholine release at 0.1 μM (118 ± 12.4%). Concentration- response curves of NMDA-evoked acetylcholine release in sham-operated rats could be superimposed on those observed in the contralateral striatum of the 6-hydroxydopamine-lesioned animals. The present data support the view of an increased glutamatergic regulation of striatal acetylcholine release via pre- and postsynaptic NMDA receptors during Parkinson's disease.
In vitro evidence for increased facilitation of striatal acetylcholine release via pre- and postsynaptic NMDA receptors in hemiparkinsonian rats
MARTI, Matteo;SBRENNA, SIMONE;BIANCHI, Clementina;BEANI, Lorenzo;MORARI, Michele
1999
Abstract
The NMDA-evoked acetylcholine release from striatal slices and synaptosomes was investigated in rats subjected to unilateral injection of 6- hydroxydopamine into the substantia nigra. In slices prepared from the striatum contralateral to the lesion, the NMDA-evoked endogenous acetylcholine release was not significant at 10 μM NMDA and maximal at 100 μM NMDA (124 ± 19%). Conversely, in slices taken from the dopamine-depleted striatum, NMDA was effective even at 10 μM (41 ± 4%), and at 100 μM (196 ± 24%) efficacy was nearly doubled. In synaptosomes prepared from the contralateral striatum, NMDA maximally stimulated 20 mM KCl-induced endogenous acetylcholine release at 1 μM (66 ± 5.1%), with lower concentrations (0.01-0.1 μM) being ineffective. Conversely, in synaptosomes prepared from the dopamine-depleted striatum, NMDA maximally enhanced the K+-evoked acetylcholine release at 0.1 μM (118 ± 12.4%). Concentration- response curves of NMDA-evoked acetylcholine release in sham-operated rats could be superimposed on those observed in the contralateral striatum of the 6-hydroxydopamine-lesioned animals. The present data support the view of an increased glutamatergic regulation of striatal acetylcholine release via pre- and postsynaptic NMDA receptors during Parkinson's disease.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
