NC-1900, an arginine-vasopressin analogue, ameliorates social behavior deficits and hyperlocomotion in MK-801-treated rats: therapeutic implications for schizophrenia.
We previously reported that chronic administration of N-methyl-D-aspartate (NMDA) antagonists reduced the density of vasopressin V1a receptors in several brain regions in rats that demonstrated social interaction deficits and increased locomotor activity. These observations indicate the ability of arginine-vasopressin (AVP), or its analogues, to modulate behavioral abnormalities associated with blockade of NMDA receptors. The present study was performed to investigate the effect of NC-1900, an AVP analogue, on social behavior and locomotor activity in rats treated with MK-801, a non-competitive NMDA receptor antagonist. Male Wistar rats were administered MK-801 (0.13 mg/kg/day ip) or saline for 14 days. Social behavior and locomotor activity were measured 45 min after the injection of NC-1900 (10 ng/kg sc) or saline together with the last MK-801 or vehicle administration. Social interaction was quantified by an automated video-tracking system, and stereotyped behavior and ataxia were manually measured. Acute administration of NC-1900 partially reversed MK-801-induced hyperlocomotion and deficits in social interaction, while NC-1900 itself did not affect these behavioral measures in animals chronically treated with vehicle saline. These results suggest that the central AVP system may interact with glutamatergic and dopaminergic transmissions, and indicate potential therapeutic effects of AVP analogues on positive and negative symptoms of schizophrenia.
Matsuoka
Tadasu
T
Department of Neuropsychiatry, Toyama Medical and Pharmaceutical University School of Medicine, 2630 Sugitani, Toyama 930-0194, Japan.
Sumiyoshi
Tomiki
T
Tanaka
Kodai
K
Tsunoda
Masahiko
M
Uehara
Takashi
T
Itoh
Hiroko
H
Kurachi
Masayoshi
M
D000704:Analysis of Variance; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D001259:Ataxia / Q000503:physiopathology; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000188:drug therapy; D012920:Social Behavior Disorders / Q000188:drug therapy*; D013239:Stereotyped Behavior / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; C115056:NC 1900; D009842:Oligopeptides; D001127:Arginine Vasopressin; D016291:Dizocilpine Maleate; D011761:Pyrrolidonecarboxylic Acid