title: Dopaminergic modulation of early signs of excitotoxicity in visualized rat neostriatal neurons.
abstract: Cell swelling induced by activation of excitatory amino acid receptors is presumably the first step in a toxic cascade that may ultimately lead to cell death. Previously we showed that bath application of N-methyl-D-aspartate (NMDA) or kainate (KA) produces swelling of neostriatal cells. The present experiments examined modulation of NMDA and KA-induced cell swelling by dopamine (DA) and its receptor agonists. Nomarski optics and infra-red videomicroscopy were utilized to visualize neostriatal medium-sized neurons in thick slices from rat pups (12-18 postnatal days). Increase in somatic cross-sectional area served as the indicator of swelling induced by bath application of glutamate receptor agonists. NMDA induced cell swelling in a dose-dependent manner. Activation of DA receptors in the absence of NMDA did not produce swelling. DA and the D1 receptor agonist SKF 38393, increased the magnitude of swelling produced by NMDA. This effect was reduced in the presence of the D1 receptor antagonist, SCH 23390. In contrast, activation of D2 receptors by quinpirole decreased the magnitude of NMDA-induced cell swelling. DA slightly attenuated cell swelling induced by activation of KA receptors. Quinpirole produced a significant concentration-dependent reduction in KA-induced swelling while SKF38393 increased KA-induced swelling, but only at a low concentration of KA. Together, these results provide additional support for the hypothesis that the direction of DA modulation depends on the glutamate receptor subtype, as well as the DA receptor subtype activated. One possible consequence of these observations is that endogenous DA may be an important contributing factor in the mechanisms of cell death in Huntington's disease.
authors.affiliation: Mental Retardation Research Center, University of California, Los Angeles 90024-1759, USA.
authors.forename: C
authors.initials: C
authors.lastname: Cepeda
authors.forename: C S
authors.initials: CS
authors.lastname: Colwell
authors.forename: J N
authors.initials: JN
authors.lastname: Itri
authors.forename: E
authors.initials: E
authors.lastname: Gruen
authors.forename: M S
authors.initials: MS
authors.lastname: Levine
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000633:toxicity; D018715:Microscopy, Video; D016202:N-Methylaspartate / Q000633:toxicity; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018690:Excitatory Amino Acid Agonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D016202:N-Methylaspartate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D007608:Kainic Acid; D004298:Dopamine