A role for 5-ht6 receptors in retention of spatial learning in the Morris water maze

This study investigates the effect of intracerebroventricular administration of a 5-ht(6) antisense oligonucleotide, (AC) complementary to bases 1-18 of the rat 5-ht(6) cDNA initiation sequence (Mol. Pharmacol. 43 (1993) 320) (1.5 mug twice daily for six days) and i.p. injection of a selective 5-ht(6) receptor antagonist Ro 04-6790 (10 or 30 mg/kg once daily for three days) on acquisition and retention in the Morris water maze. Neither the 5-ht6 AO (which reduced cortical ['H]-LSD binding sites by 10-16%) nor Ro 04C, 6790 affected acquisition, but both enhanced retention of the learned platform position such that rats spent significantly longer searching the trained platform position than any other area during the probe tests. Furthermore, neither AO nor Ro 04-6790 had any effect on the time taken to reach a raised visible platform, indicating that visual acuity was unimpaired. In addition, AO reduced both food consumption and body weight and the later effect was also seen following Ro 04-6790, suggesting a role for the 5-ht(6) receptor in the regulation of feeding. Hence, while the underlying mechanism remains unclear, enhanced retention of spatial learning following both AO and 5-ht(6) antagonist administration strongly indicate a role for this receptor in memory processes. (C) 2001 Elsevier Science Ltd. All rights reserved.