title: N-methyl-D-aspartate-R1 receptor antisense oligodeoxynucleotide modulates pre- and postsynaptic expression of D2 dopamine receptors in the rat.
abstract: To elucidate the relationship between glutamatergic and dopaminergic transmissions, the effects of antisense oligodeoxynucleotide (aODN) to mRNA of NR1 subunit of N-methyl-D-aspartate (NMDA) receptors on the expression of dopamine D(2) receptors (DRD(2)) were examined. Rats received continuous intracerebroventricular administration (20 nmol /day, for 7 days) of aODN or sense ODN (sODN), or of the same amount of saline. In vitro receptor autoradiography revealed that NR1 aODN induced a significant decrease in specific [(3)H]YM-09151-2 binding in the substantia nigra as compared to sODN and saline. Non-significant decreases were also seen in the ventral tegmental area. Northern blot analysis demonstrated a significant increase in DRD(2) mRNA expression in the striata of aODN-treated animals. These results suggest that specific inhibition of NMDA receptor expression modulates pre- and post-synaptic expression of DRD(2), possibly via reduced nigrostriatal dopaminergic activity.
authors.affiliation: Department of Neuropsychiatry, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Murata
authors.forename: Michio
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kodai
authors.initials: K
authors.lastname: Tanaka
authors.forename: Koji
authors.initials: K
authors.lastname: Tajiri
authors.forename: Kenji
authors.initials: K
authors.lastname: Emori
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kurachi
mesh_terms: D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000494:pharmacology; D015152:Blotting, Northern; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001549:Benzamides; D018492:Dopamine Antagonists; C409466:NR1 NMDA receptor; D016376:Oligonucleotides, Antisense; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; C030265:nemonapride