Cannabidiol and clozapine reverse MK-801-induced deficits in social interaction and hyperactivity in Sprague-Dawley rats

J Psychopharmacol. 2012 Oct;26(10):1317-32. doi: 10.1177/0269881112441865. Epub 2012 Apr 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Attention / drug effects
  • Attention Deficit Disorder with Hyperactivity / chemically induced
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / etiology
  • Attention Deficit Disorder with Hyperactivity / prevention & control
  • Behavior, Animal / drug effects
  • Cannabidiol / therapeutic use*
  • Clozapine / administration & dosage
  • Clozapine / therapeutic use*
  • Disease Models, Animal*
  • Dizocilpine Maleate
  • Dose-Response Relationship, Drug
  • Male
  • Motor Activity / drug effects
  • Psychomotor Agitation / drug therapy
  • Psychomotor Agitation / etiology
  • Psychomotor Agitation / prevention & control
  • Psychotropic Drugs
  • Rats
  • Rats, Sprague-Dawley
  • Schizophrenia / chemically induced
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Schizophrenia / prevention & control
  • Social Behavior
  • Social Behavior Disorders / chemically induced
  • Social Behavior Disorders / drug therapy*
  • Social Behavior Disorders / etiology
  • Social Behavior Disorders / prevention & control

Substances

  • Antipsychotic Agents
  • Psychotropic Drugs
  • Cannabidiol
  • Dizocilpine Maleate
  • Clozapine