title: Extracellular levels of glutamate and aspartate in the entopeduncular nucleus of the rat determined by microdialysis: regulation by striatal dopamine D2 receptors via the indirect striatal output pathway?
abstract: This study used intracerebral microdialysis to monitor the outputs of excitatory amino acids in the entopeduncular nucleus (EPN) of conscious or halothane-anaesthetized rats, in an attempt to obtain direct biochemical evidence for the theory that neuronal inputs to the EPN by the indirect striatal output pathway are glutamatergic and regulated primarily by dopamine D2 receptors in the striatum. In dopamine-intact animals, both glutamate and asparate were readily detectable in EPN dialysates. Recoveries of both amino acids were increased bilaterally by local perfusion with veratridine (100 microM, given under halothane anaesthesia), pretreatment with reserpine (4 mg/kg, i.p., 24 h beforehand), unilateral pretreatment of the medial forebrain bundle with 6-OHDA (8 microg/4 microl), and by the systemic (1 mg/kg, i.p.) or bilateral intrastriatal (7 microg/0.5 microl under halothane anaesthesia) administration of the dopamine D2 receptor antagonist haloperidol, but not raclopride (2 mg/kg, i.p.). The dopamine D1 receptor antagonist SCH 23390 was ineffective both systemically (0.25 mg/kg, i.p.) and intrastriatally (0.125 microg/0.5 microl/side), as also were control intrastriatal injections of saline (0.5 microl/side). By contrast, the dopamine D2/3 receptor agonist quinpirole (4 mg/kg, i.p.) lowered the outputs of glutamate and aspartate in the EPN of reserpine-treated and normal individuals, whilst the dopamine D1 receptor agonist SKF 38393 (30 mg/kg, i.p.) was inactive; however, both drugs caused behavioural arousal. The dopamine D2/3 receptor agonist RU 24213 reversed reserpine-induced akinesia, yet paradoxically increased glutamate (not aspartate) output in the EPN still further. The combination of benserazide (30 mg/kg, i.p.) and L-DOPA (50 mg/kg, i.p.) evoked intense contraversive circling in unilaterally 6-OHDA-lesioned rats, together with a drop in EPN glutamate (but not aspartate) output in the intact but not lesioned hemisphere. These results offer biochemical support for the hypothesis that excitatory neurones innervating the EPN via the indirect striatal output pathway, may utilise glutamate and/or aspartate as their neurotransmitter. They further endorse the view that the EPN receives information from striatal D2 and not D1 receptors via excitatory synapses, which become hyperactive following dopamine depletion or inactivation, and which are subject to control by the contralateral as well as by the ipsilateral hemisphere. The results obtained with RU 24213 and L-DOPA, however, indicate that dopaminergic behaviours can also occur independently of glutamate or aspartate release in the EPN.
authors.affiliation: Department of Pharmacology, School of Pharmacy, London, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Biggs
authors.forename: L J
authors.initials: LJ
authors.lastname: Fowler
authors.forename: P S
authors.initials: PS
authors.lastname: Whitton
authors.forename: M S
authors.initials: MS
authors.lastname: Starr
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D003342:Corpus Striatum / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001224:Aspartic Acid; D018698:Glutamic Acid; D014701:Veratridine; D012110:Reserpine; D016627:Oxidopamine