title: A within-subjects microdialysis/behavioural study of the role of striatal acetylcholine in D1-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) D2 receptor agonist quinpirole and the A2A 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 D1 receptor agonist CY 208-243. Administration of CY 208-243 (75, 100 and 200 microg/kg) to 6-OHDA-lesioned rats dose-dependently stimulated ACh release and induced contralateral turning. MK-801 (50 and 100 microg/kg) reduced basal ACh release (max 22%) and did not elicit any turning. MK-801 (50 and 100 microg/kg) potentiated the contralateral turning, but failed to modify the stimulation of ACh release elicited by 100 and 200 microg/kg of CY 208-243. MK-801 (100 microg/kg) prevented the increase in striatal ACh release evoked by the lower dose of CY 208-243 (75 microg/kg) but contralateral turning was not observed. The D2 receptor agonist quinpirole (30 and 60 microg/kg) elicited low-intensity contralateral turning and decreased basal ACh release. Quinpirole potentiated the D1-mediated contralateral turning behaviour elicited by CY 208-243 (100 microg/kg), but failed to affect the increase in ACh release elicited by the D1 agonist. The adenosine A2A receptor antagonist SCH 58261 (1 microg/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 D2 receptors by quinpirole and blockade of adenosine A2A receptors by SCH 58261 potentiate the D1-mediated contralateral turning behaviour in DA denervated rats without affecting the action of the D1 agonist on ACh release. These observations do not support the hypothesis that the potentiation of D1-dependent contralateral turning by MK-801, quinpirole or SCH 58261 is mediated by changes in D1-stimulated release of ACh in the striatum.
authors.affiliation: Department of Toxicology and CNR-Center for Neuropharmacology, University of Cagliari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Acquas
authors.forename: S
authors.initials: S
authors.lastname: Fenu
authors.forename: P
authors.initials: P
authors.lastname: Loddo
authors.forename: G
authors.initials: G
authors.lastname: Di Chiara
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D017551:Microdialysis; D017072:Neostriatum / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology*; D013563:Sympathectomy, Chemical; D014230:Triazoles / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D000316:Adrenergic alpha-Agonists; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D018696:Neuroprotective Agents; D010617:Phenanthridines; D011743:Pyrimidines; D018341:Receptors, Adrenergic, alpha-2; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014230:Triazoles; C054531:CY 208-243; D019257:Quinpirole; D016291:Dizocilpine Maleate; D001058:Apomorphine; D000109:Acetylcholine