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Protection of striatal neurons by joint blockade of D1 and D2 receptor subtypes in an in vitro model of cerebral hypoxia

Lookup NU author(s): Dr Sue Davis


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Massive increases in extracellular dopamine have been reported in the ischemic rodent striatum, implicating this neurotransmitter in toxic events. We have examined whether dopamine receptor antagonists are protective against hypoxic insult, using brain slices containing the rostral striatum obtained from adult male C57/BLIcrfat mice. Slices were subjected in vitro to 20 min nitrogen hypoxia, with or without addition of: (i) 50 μM haloperidol (D2 receptor antagonist and sigma ligand), (ii) 10 μM SCH23390 (selective D1 receptor antagonist), (iii) 10 μM eticlopride (selective D2 receptor antagonist), (iv) 10 μM SCH23390 and 10 μM eticlopride in combination, and (v) 10 μM MK-801 (noncompetitive NMDA receptor antagonist). Subsequently, slices were reoxygenated, fixed 2 h postinsult, and processed for light microscopy. Damage was assessed by calculating pyknotic profiles as a percentage of total neuronal profiles present. No pyknotic profiles were detected in normoxic control tissue, but this phenotype predominated in most slices subject to hypoxia alone (60.1 ± 30.6% pyknotic profiles). Marked protection was produced by haloperidol (7.1 ± 7.6%, P = 0.002), MK-801 (8.6 ± 6.9%, P = 0.007), and the combined application of SCH23390 and eticlopride (5.9 ± 9.4%, P = 0.001). No protection was demonstrated for SCH23390 or eticlopride when applied separately. These data suggest that hypoxic damage in the rostral mouse striatum is mediated via NMDA, D1, and D2 receptors. Protection against hypoxic damage by dopamine receptor antagonists requires the combined blockade of both classes of dopamine receptor. © 2002 Elsevier Science (USA).

Publication metadata

Author(s): Davis S, Brotchie J, Davies I

Publication type: Article

Publication status: Published

Journal: Experimental Neurology

Year: 2002

Volume: 176

Issue: 1

Pages: 229-236

ISSN (print): 0014-4886

ISSN (electronic): 1090-2430

Publisher: Academic Press


DOI: 10.1006/exnr.2002.7926

PubMed id: 12093100


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