title: Cannabidiol and clozapine reverse MK-801-induced deficits in social interaction and hyperactivity in Sprague-Dawley rats.
abstract: Recently, a novel paradigm has been designed to assess social investigative behaviour in pairs of Sprague-Dawley rats, which involves physical separation whilst ensuring they are able to maintain contact through other social cues. We have modified this set-up in order to assess not just social behaviour but also locomotor activity of the rats. Results showed that the MK-801- (0.3 mg/kg) treated rats displayed reduced social investigative behaviour, hyperactivity as well as reduced attention span. Pretreatment with the phytocannabinoid cannabidiol (3 mg/kg) not only normalised social investigative behaviour but increased it beyond control levels. Pretreatment with clozapine (1, 3 mg/kg) also normalised social investigative behaviour. Both cannabidiol and clozapine inhibited MK-801-induced hyperactivity. However, there were no effects of pretreatment on impairments to attention span. Our findings reinforce several aspects of the validity of the MK-801-induced model of social withdrawal and hyperactivity and also support the use of this novel set-up for further investigations to assess the antipsychotic potential of novel compounds.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia. anand.gururajan@monash.edu.au
authors.forename: Anand
authors.initials: A
authors.lastname: Gururajan
authors.forename: David A
authors.initials: DA
authors.lastname: Taylor
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Malone
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D001522:Behavior, Animal / Q000187:drug effects; D002185:Cannabidiol / Q000627:therapeutic use*; D003024:Clozapine / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011595:Psychomotor Agitation / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D011619:Psychotropic Drugs; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D012919:Social Behavior; D012920:Social Behavior Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control
chemical_list: D014150:Antipsychotic Agents; D011619:Psychotropic Drugs; D002185:Cannabidiol; D016291:Dizocilpine Maleate; D003024:Clozapine