title: Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment.
abstract: BACKGROUND
  New pharmacological treatments for the cognitive deficits in schizophrenia are needed. Tetrahydroprotoberberines, such as govadine, are one class of compounds with dopaminergic activities that may be useful in treating some aspects of the cognitive symptoms of the disorder.
  
  
  OBJECTIVE
  The objective of the present studies was to test the effects of the D- and L-enantiomers of govadine on the impairment in a paired-associate learning (PAL) task produced by acute MK-801 in rats. We also assessed effects of the typical antipsychotic haloperidol as a comparator compound.
  
  
  METHODS
  MK-801 (0.05, 0.1, 0.15, and 0.2 mg/kg), D- and L-govadine (0.3, 1.0, and 3.0 mg/kg), and haloperidol (0.05, 0.1, and 0.25 mg/kg) were administered acutely to rats well trained on the PAL task in touchscreen-equipped operant conditioning chambers.
  
  
  RESULTS
  Acute MK-801 impaired performance of PAL in a dose-dependent manner by reducing accuracy and increasing correction trials. L-Govadine (1.0 mg/kg), but not D-govadine, blocked the disruptive effects of MK-801 (0.15 mg/kg) on PAL. Haloperidol failed to affect the MK-801-induced disruption of PAL. Higher doses of L-govadine and haloperidol dramatically impaired performance of the task which confounded interpretation of cognitive outcomes.
  
  
  CONCLUSIONS
  L-Govadine appears unique in its ability to improve performance of the MK-801-induced impairment in the PAL task. This behavioral effect may relate the ability of L-govadine to antagonize dopamine D2 receptors while also promoting dopamine efflux. Future research should further characterize the role of the dopamine system in the rodent PAL task to elucidate the mechanisms of its pro-cognitive effects.
authors.affiliation: Department of Physiology, University of Saskatchewan, GB33, Health Sciences Building, 107 Wiggins Rd, Saskatoon, SK, Canada, S7N 5E5.
authors.forename: Brittney R
authors.initials: BR
authors.lastname: Lins
authors.affiliation: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada, V6T 2A1.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Phillips
authors.affiliation: Department of Physiology, University of Saskatchewan, GB33, Health Sciences Building, 107 Wiggins Rd, Saskatoon, SK, Canada, S7N 5E5. john.howland@usask.ca.
authors.forename: John G
authors.initials: JG
authors.lastname: Howland
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001600:Berberine Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D010153:Paired-Associate Learning / Q000187:drug effects* / Q000502:physiology; D010775:Photic Stimulation / Q000379:methods*; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D001600:Berberine Alkaloids; D017448:Receptors, Dopamine D2; C103305:govadine; D016291:Dizocilpine Maleate
keywords: Antipsychotic; Cognition; Dopamine receptor; Haloperidol; NMDA receptor; Schizophrenia