Role of 5-HT1A receptors in a mouse passive avoidance paradigm

The effect on memory processes of modulation of 5-HT1A receptor subtype was investigated in the mouse passive avoidance test. The administration of 5- HT1A-receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-2-phthalimmido) butyl]piperazine) and WAY-100635 (N-[2-14-(2-methoxyphenyl)-1-piperazinyl]e thyl]-N-2-pyridinyl-cyclohexanecarboxamide) produced a dose-dependent amnes ic effect comparable to that obtained with the well-known amnesic agents sc opolamine and dicyclomine. Pretreatment with the 5-HT1A-receptor agonists 8 -OH-DPAT ((+/-)-8-hydroxy-dipropylaminotetralin) and 5-CT (5-carboxamidotry ptamine) dose-dependently prevented the amnesia induced by 5-HT1A antagonis ts, scopolamine, dicyclomine and exposure to an hypoxic environment. The an tiamnesic effect exerted by 5-HT1A-receptor agonists was comparable to that produced by the nootropic drug piracetam and cholinesterase inhibitor phys ostigmine. At effective doses, neither 5-HT1A-receptor agonists nor 5-HT1A- receptor antagonists produced any impairment of mouse motor coordination (r ota-rod test), spontaneous motility (Animex apparatus) and inspection activ ity (hole board). These results indicate that modulation of 5-HT1A-receptor s appears to play an important role in the regulation of cognitive processe s.