• D1-like receptor activation improves PCP-induced cognitive deficits in animal models: Implications for mechanisms of improved cognitive function in schizophrenia

      McLean, Samantha L.; Idris, Nagi F.; Woolley, M.L.; Neill, Joanna C. (2009-06)
      Phencyclidine (PCP) produces cognitive deficits of relevance to schizophrenia in animal models. The aim was to investigate the efficacy of the D1-like receptor agonist, SKF-38393, to improve PCPinduced 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 (Pb0.01) an effect significantly antagonised by SCH-23390 (0.05 mg/kg), a D1-like receptor antagonist (Pb0.01). In the RL task sub-chronic PCP significantly reduced performance in the reversal phase (Pb0.001); SKF-38393 (6.0 mg/kg) improved this PCPinduced deficit, an effect antagonised by SCH-23390 (Pb0.05). These results suggest a role for D1-like receptors in improvement of cognitive function in paradigms of relevance to schizophrenia.