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

In rats lesioned with 6-hydroxydopamine (6-OHDA) the effect of the noncompe titive N-methyl D-aspartate (NMDA) receptor antagonist, MK-801, the dopamin e (DA) D-2 receptor agonist quinpirole and the A(2A) adenosine antagonist S CH 58261 was studied on acetylcholine (ACh) release in the lesioned striatu m and contralateral turning behaviour stimulated by the administration of t he DA D-2 receptor agonist CY 208-243. Administration of CY 208-243 (75, 10 0 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) redu ced 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 modif y 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 ev oked 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 releas e. 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 antag onist SCH 58261 (1 mg/kg i.v.) failed per se to elicit contralateral turnin g behaviour. SCH 58261 potentiated the contraversive turning induced by CY 208-243 but failed to affect the increase of ACh release. The results of th e present study indicate that blockade of NMDA receptors by MK-801, stimula tion of DA D-2 receptors by quinpirole and blockade of adenosine A(2A) rece ptors by SCH 58261 potentiate the D-1-mediated contralateral turning behavi our in DA denervated rats without affecting the action of the D-1 agonist o n ACh release. These observations do not support the hypothesis that the po tentiation 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 st riatum. (C) 1999 Elsevier Science B.V. All rights reserved.