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.