Yes / 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.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/8466 |
| Date | 21 July 2009 |
| Creators | McLean, Samantha L., Woolley, M.L., Thomas, D., Neill, Joanna C. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted Manuscript |
| Rights | The final publication is available at Springer via http://dx.doi.org/10.1007/s00213-009-1618-0 |
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