Effect of MK-801 on gene expressions in the amygdala of rats.
Rodents treated with N-methyl-D-aspartate (NMDA) antagonists have been thought to be an animal model of schizophrenia. In this study, we examined gene expression in the amygdala of rats chronically treated with MK-801, as well as behavioral changes, such as social behavior, in these animals. The social interaction test, a measure of social behavior, and locomotor activity was performed in male Wistar rats injected with MK-801 (0.13 mg/kg i.p.) or saline for 14 days. Changes in mRNA levels were analyzed using a GeneChip microarray system. Real-time quantitative PCR (RT-qPCR) assay was subsequently conducted to confirm the results of the microarray analysis. MK-801 decreased social interaction and increased locomotor activity in rats, consistent with previous reports. We found 23 downregulated genes and 16 upregulated genes, with the gene encoding arginine-vasopressin (AVP) being most downregulated, and that for transthyretin (Ttr) most upregulated. mRNA levels, quantified by RT-qPCR assay, were altered for genes related to neuropeptides (AVP, Sstr2), the arachidonic cascade (Ptgds), myelination (Mobp, Enpp2), neurotrophic factors (Igfbp2), and hormonal milieu (Ttr). Downregulation of the AVP gene in the amygdala of MK-801-treated rats may provide a basis for the ability of AVP-analogues to ameliorate the behavioral disturbances caused by blockade of the NMDA receptor. The results of this study provide an insight into the neural substrates responsible for the generation of psychotic symptoms.
Matsuoka
Tadasu
T
Department of Neuropsychiatry, University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Tsunoda
Masahiko
M
Sumiyoshi
Tomiki
T
Takasaki
Ichiro
I
Tabuchi
Yoshiaki
Y
Seo
Tomonori
T
Tanaka
Kodai
K
Uehara
Takashi
T
Itoh
Hiroko
H
Suzuki
Michio
M
Kurachi
Masayoshi
M
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016291:Dizocilpine Maleate