A within-subjects microdialysis/behavioural study of the role of striatal acetylcholine in D 1-dependent turning

Abstract

In rats lesioned with 6-hydroxydopamine (6-OHDA) the effect of the noncompetitive N-methyl d-aspartate (NMDA) receptor antagonist, MK-801, the dopamine (DA) D 2 receptor agonist quinpirole and the A 2A adenosine antagonist SCH 58261 was studied on acetylcholine (ACh) release in the lesioned striatum and contralateral turning behaviour stimulated by the administration of the DA D 1 receptor agonist CY 208-243. Administration of CY 208-243 (75, 100 and 200 μg/kg) to 6-OHDA-lesioned rats dose-dependently stimulated ACh release and induced contralateral turning. MK-801 (50 and 100 μg/kg) reduced basal ACh release (max 22%) and did not elicit any turning. MK-801 (50 and 100 μg/kg) potentiated the contralateral turning, but failed to modify the stimulation of ACh release elicited by 100 and 200 μg/kg of CY 208-243. MK-801 (100 μg/kg) prevented the increase in striatal ACh release evoked by the lower dose of CY 208-243 (75 μg/kg) but contralateral turning was not observed. The D 2 receptor agonist quinpirole (30 and 60 μg/kg) elicited low-intensity contralateral turning and decreased basal ACh release. Quinpirole potentiated the D 1-mediated contralateral turning behaviour elicited by CY 208-243 (100 μg/kg), but failed to affect the increase in ACh release elicited by the D 1 agonist. The adenosine A 2A receptor antagonist SCH 58261 (1 mg/kg i.v.) failed per se to elicit contralateral turning behaviour. SCH 58261 potentiated the contraversive turning induced by CY 208-243 but failed to affect the increase of ACh release. The results of the present study indicate that blockade of NMDA receptors by MK-801, stimulation of DA D 2 receptors by quinpirole and blockade of adenosine A 2A receptors by SCH 58261 potentiate the D 1-mediated contralateral turning behaviour in DA denervated rats without affecting the action of the D 1 agonist on ACh release. These observations do not support the hypothesis that the potentiation of D 1-dependent contralateral turning by MK-801, quinpirole or SCH 58261 is mediated by changes in D 1-stimulated release of ACh in the striatum.