A within-subjects microdialysis/behavioural study of the role of striatal acetylcholine in D1-dependent turning

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-2 receptor agonist CY 208-243. Administration of CY 208-243 (75, 100 and 200 mu g/kg) to 6-OHDA-lesioned rats dose-dependently stimulated ACh release and induced contralateral turning. MK-801 (50 and 100 mu g/kg) reduced basal ACh release (max 22%) and did not elicit any turning. MK-801 (50 and 100 mu g/kg) potentiated the contralateral turning, but failed to modify the stimulation of ACh release elicited by 100 and 200 mu g/kg of CY 208-243. MK-801 (100 mu g/kg) prevented the increase in striatal ACh release evoked by the lower dose of CY 208-243 (75 mu g/kg) but contralateral turning was not observed. The D-2 receptor agonist quinpirole (30 and 60 mu g/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 mu g/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. (C) 1999 Elsevier Science B.V. All rights reserved.