Social Interaction Deficits Caused by Chronic Phencyclidine Administration are Reversed by Oxytocin

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 30; no. 10; pp. 1883 - 1894
• Main Authors: LEE, Paul R, BRADY, Dana L, SHAPIRO, Robert A, DORSA, Daniel M, KOENIG, James I
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01-10-2005; Nature Publishing Group
• Subjects: Adaptation, Physiological - drug effects; Analysis of Variance; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Dose-Response Relationship, Drug; Drug addictions; Drug Administration Schedule; Drug Interactions; Exploratory Behavior - drug effects; Gene Expression Regulation - drug effects; Hallucinogens - administration & dosage; In Situ Hybridization - methods; Interpersonal Relations; Male; Medical sciences; Oxytocin - genetics; Oxytocin - metabolism; Oxytocin - therapeutic use; Phencyclidine - administration & dosage; Radioligand Assay - methods; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Social Behavior Disorders - chemically induced; Social Behavior Disorders - drug therapy; Time Factors; Toxicology; Vasopressins - genetics; Vasopressins - metabolism; Rat; Psychotropic; Toxicity; Central nervous system; Schizophrenia; social interaction; schizophrenia; NMDA receptor; Glutamate receptor; Hypothalamus; Encephalon; Psychosis; Phencyclidine; Neurohypophyseal hormone; Piperidine derivatives; Hallucinogen; Drug of abuse; Antagonist; Amygdaloid nucleus; Oxytocin; Rodentia; Basal ganglion; Neuroprotective agent; Vertebrata; Chronic; Mammalia; Social interaction; Animal; Reversibility; Oxytocin(drug); NMDA receptor; oxytocin; amygdala; rats; hypothalamus
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/sj.npp.1300722

Chronic administration of phencyclidine (PCP) has been advanced as a valid animal model of the social deficit symptoms of schizophrenia. In these studies, the cumulative time that male rats treated once a day for 14 days with PCP actively engaged in social behavior was decreased approximately 75% relative to saline-treated control animals. In addition, these socially impaired rats had an increase in the relative amount of noncontact interactions compared with saline-injected peers. Social behaviors were preferentially affected by PCP treatment because in two anxiety-related behavioral assays, the open field and light/dark emergence tests, there was a failure to differentiate between the PCP-treated rats and saline-injected control rats. Considering the general importance of the neuropeptides oxytocin and vasopressin in male social behaviors, studies of molecular markers related to these neuropeptides were performed. Hypothalamic oxytocin mRNA expression was significantly decreased while oxytocin receptor binding was increased in the central nucleus of the amygdala following chronic PCP treatment. Given the significance of central nucleus of the amygdala in social behavior, oxytocin was infused into the central nucleus of experimental and control male rats, and their postinfusion social interaction and open field behaviors were analyzed. A bilateral infusion of 1 mug of oxytocin into the central amygdala selectively restored the normal quantity and quality of social behavior in chronic PCP-treated male rats without altering open field behaviors. These findings suggest that deficits in the central oxytocinergic system may underlie the social impairment exhibited in this animal model of schizophrenia.