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-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide) produced a dose-dependent amnesic effect comparable to that obtained with the well-known amnesic agents scopolamine and dicyclomine. Pretreatment with the 5-HT1A-receptor agonists 8-OH-DPAT ((+/-)-8-hydroxy-dipropylaminotetralin) and 5-CT (5-carboxamidotryptamine) dose-dependently prevented the amnesia induced by 5-HT1A antagonists, scopolamine, dicyclomine and exposure to an hypoxic environment. The antiamnesic effect exerted by 5-HT1A-receptor agonists was comparable to that produced by the nootropic drug piracetam and cholinesterase inhibitor physostigmine. At effective doses, neither 5-HT1A-receptor agonists nor 5-HT1A-receptor antagonists produced any impairment of mouse motor coordination (rota-rod test), spontaneous motility (Animex apparatus) and inspection activity (hole board). These results indicate that modulation of 5-HT1A-receptors appears to play an important role in the regulation of cognitive processes.