D(1)-like receptor activation improves PCP-induced cognitive deficits in animal models: Implications for mechanisms of improved cognitive function in schizophrenia

Eur Neuropsychopharmacol. 2009 Jun;19(6):440-50. doi: 10.1016/j.euroneuro.2009.01.009. Epub 2009 Mar 5.


Phencyclidine (PCP) produces cognitive deficits of relevance to schizophrenia in animal models. The aim was to investigate the efficacy of the D(1)-like receptor agonist, SKF-38393, to improve PCP-induced deficits in the novel object recognition (NOR) and operant reversal learning (RL) tasks. Rats received either sub-chronic PCP (2 mg/kg) or vehicle for 7 days, followed by a 7-day washout. Rats were either tested in NOR or the RL tasks. In NOR, vehicle rats successfully discriminated between novel and familiar objects, an effect abolished in PCP-treated rats. SKF-38393 (6 mg/kg) significantly ameliorated the PCP-induced deficit (P<0.01) an effect significantly antagonised by SCH-23390 (0.05 mg/kg), a D(1)-like receptor antagonist (P<0.01). In the RL task sub-chronic PCP significantly reduced performance in the reversal phase (P<0.001); SKF-38393 (6.0 mg/kg) improved this PCP-induced deficit, an effect antagonised by SCH-23390 (P<0.05). These results suggest a role for D(1)-like receptors in improvement of cognitive function in paradigms of relevance to schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / therapeutic use
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects
  • Benzazepines / pharmacology
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / metabolism*
  • Conditioning, Operant / drug effects
  • Disease Models, Animal
  • Dopamine Agonists / pharmacology
  • Dopamine Agonists / therapeutic use
  • Dopamine Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Neuropsychological Tests
  • Phencyclidine*
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / metabolism*
  • Recognition, Psychology / drug effects*


  • Benzazepines
  • Dopamine Agonists
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • SCH 23390
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Phencyclidine