title: N-Methyl-D-aspartate receptors contribute to the maintenance of dopaminergic neurons in rat midbrain slice cultures.
abstract: Excitatory neuronal activity produces beneficial influences on neuronal survival under several circumstances. We show that cultivation of rat midbrain slices in the presence of elevated extracellular Mg(2+) resulted in a marked decrease in the number of dopaminergic neurons. The effect was prominent when Mg(2+) was added to the medium during the first week of cultivation. Chronic treatment with antagonists of N-methyl-D-aspartate receptors such as 2-amino-5-phosphonovaleric acid, MK-801 and ifenprodil also resulted in a marked loss of dopaminergic neurons, whereas nicotinic receptor antagonists showed no effect. The effect of MK-801 was abolished by chronic depolarization by elevated extracellular K(+), or by application of forskolin or dibutyryl cyclic AMP. Thus, tonic activation of N-methyl-D-aspartate receptors driven by neuronal activity may play an important role in the maintenance of dopaminergic neurons.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
authors.forename: Haruki
authors.initials: H
authors.lastname: Shibata
authors.forename: Chikako
authors.initials: C
authors.lastname: Takenaka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaneko
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008274:Magnesium / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D005576:Colforsin; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D012964:Sodium; D014446:Tyrosine 3-Monooxygenase; D008274:Magnesium; C010739:ifenprodil; D011188:Potassium; D004298:Dopamine