(+)-MK-801 induced social withdrawal in rats; a model for negative symptoms of schizophrenia.
Dopaminergic agonists and NMDA-receptor antagonists form the basis for the dopamine and glutamate models of schizophrenia, respectively. In human subjects dopaminergic agonists evoke a psychosis resembling positive symptoms of schizophrenia, while NMDA-receptor antagonists produce both positive and negative symptoms. Consequently, the glutamate model may be considered the most complete of the two models. Alterations in animal behaviour, in response to amphetamine or NMDA-receptor antagonists, are widely used to model schizophrenia. NMDA-receptor antagonist induced social withdrawal in rat is an established model for negative symptoms of schizophrenia. In this study we have set up an automated method, based on video tracking, to assess social behaviour, motor activity and movement pattern in rats. This method was then used to evaluate the effects of amphetamine and the NMDA-receptor antagonist (+)-MK-801, administered as single intraperitoneal injections, on rat behaviour. Amphetamine caused significantly increased motor activity and a tendency towards stimulation of social interactions. (+)-MK-801 also stimulated motor activity, but induced a significant inhibition of social interactions. These results indicate that a single injection of (+)-MK-801 to rats models both positive and negative symptoms of schizophrenia. Amphetamine, in contrast, reflects only the positive symptoms of schizophrenia in this model.
Rung
Johan P
JP
The Arvid Carlsson Institute for Neuroscience, Institute of Clinical Neuroscience, The Sahlgrenska Academy, Göteborg University, Medicinaregatan 11, SE-405 30 Göteborg, Sweden. johan.rung@psychiat.gu.se
Carlsson
Arvid
A
Rydén Markinhuhta
Katarina
K
Carlsson
Maria L
ML
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012565:Schizophrenic Psychology; D012919:Social Behavior
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D003913:Dextroamphetamine