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    Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

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    McLean_Psychopharmacology.pdf (399.1Kb)
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    Publication date
    2009-10-15
    Author
    McLean, Samantha L.
    Woolley, M.L.
    Thomas, D.
    Neill, Joanna C.
    Keyword
    Reversal learning; 5-HT7; 5-HT1A; 5-HT2C receptors; Phencyclidine; Rat
    Rights
    The final publication is available at Springer via http://dx.doi.org/10.1007/s00213-009-1618-0
    Peer-Reviewed
    Yes
    
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    Abstract
    Rationale: 5-HT receptor mechanisms have been suggested to mediate improvements in cognition in schizophrenia. Aim: To investigate the involvement of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in female rats, a task of relevance to schizophrenia. Methods: Adult female hooded-Lister rats were trained to perform an operant reversal learning task and then received sub-chronic PCP (2 mg/kg) or vehicle i.p. twice daily for seven days, followed by 7-days washout. Rats then received an acute dose of the 5-HT7 receptor antagonist SB-269970A (1.0, 3.0, 10.0 mg/kg; i.p.) or vehicle. In experiment 2, PCP-treated rats received the selective 5-HT2C receptor antagonist, SB-243213A acutely (1.0, 3.0, 10.0 mg/kg; i.p.) or vehicle. In experiment 3, PCP-treated rats received the 5-HT1A receptor partial agonist, buspirone (0.15625, 0.3125, 0.625 mg/kg, i.p.) in combination with the selective 5-HT1A receptor antagonist WAY-100635 (0.3, 1.0 mg/kg). Results: In all experiments sub-chronic PCP significantly impaired reversal phase performance (P<0.01-0.001), with no effect in the initial phase. SB-269970A at 3.0 and 10.0 mg/kg significantly improved the PCP-induced deficit (P<0.05). SB-243213A also significantly attenuated the deficit at 10 mg/kg (P<0.05). In experiment 3, buspirone attenuated the deficit with significant effects at 0.3125 mg/kg and 0.625 mg/kg (P<0.05). WAY-100635 at 0.3 and 1.0 mg/kg produced a partial attenuation of buspirone’s effect as buspirone (0.3125 mg/kg) in the presence of WAY-100635 did not significantly reverse the PCP-induced deficit. Conclusions: These studies implicate the role of 5-HT7, 5-HT2C and 5-HT1A receptors in the improvement of cognitive dysfunction of relevance to schizophrenia.
    URI
    http://hdl.handle.net/10454/8466
    Version
    Accepted Manuscript
    Citation
    McLean SL, Woolley ML, Thomas D and Neill JC (2009) Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat. Psychopharmacology. 206(3): 403-414.
    Link to publisher’s version
    http://dx.doi.org/10.1007/s00213-009-1618-0
    Type
    Article
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    Life Sciences Publications

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