EFFECT OF A THYROTROPIN-RELEASING-HORMONE ANALOG, RX77368, AN AMPA-INDUCED SEPTAL HIPPOCAMPAL LESIONED RATS IN AN OPERANT DELAYED NONMATCHING TO POSITION TEST

The aim of the present study was to determine the effect of a thyrotro phin-releasing hormone (TRH) analogue, RX77368, on performance of a wo rking memory test, using a delayed non-matching to position (DNMTP) pr ocedure, in lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (A MPA)-induced septal-hippocampal lesioned rats. Following a postsurgery recovery period, pretrained rats were tested once daily on DNMTP, 30 min post-administration of RX77368 (1.0 mg kg(-1), IP) or saline. AMPA -induced lesions significantly reduced percent correct responses durin g the second week of testing. Comparison of percent correct responses between days 1 and 13 of testing showed that sham rats significantly i mproved DNMTP performance, whereas lesioned rats did not. RX77368 sign ificantly reduced general locomotor activity in sham rats in activity boxes, but did not disrupt non-mnemonic measures, such as locomotion a nd motivation, in the DMMTP test. RX77368 increased percent correct re sponses in AMPA-lesioned rats on days 8-10 and 11-13. There was also a significant improvement in percent correct responses achieved between day 1 and 13 in RX77368-treated lesioned and sham rats. These results showed that: (i) septal-hippocampal lesioned rats did not improve ove r the testing period; and (ii) on test days when a significant impairm ent was present, RX77368 partially improved DNMTP performance.