title: D(1)-like receptor activation improves PCP-induced cognitive deficits in animal models: Implications for mechanisms of improved cognitive function in schizophrenia.
abstract: 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.
authors.affiliation: Bradford School of Pharmacy, University of Bradford, Bradford, West Yorkshire BD71DP, UK. s.l.mclean@bradford.ac.uk
authors.forename: Samantha L
authors.initials: SL
authors.lastname: McLean
authors.forename: Nagi F
authors.initials: NF
authors.lastname: Idris
authors.forename: Marie L
authors.initials: ML
authors.lastname: Woolley
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Neill
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D009483:Neuropsychological Tests; D010622:Phencyclidine; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects*
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D010622:Phencyclidine