Jpn. J. Pharmacol. 84 (4), 418-424 (2000)

Role of 5-HT_1A Receptors in a Mouse Passive Avoidance Paradigm

Nicoletta Galeotti, Carla Ghelardini* and Alessandro Bartolini

Department of Pharmacology, University of Florence, Viale G. Pieraccini 6, I-50139 Florence, Italy
*Corresponding author.ﾊﾊFAX:+39-55-4271280
E-mail: ghelard@server1.pharm.unifi.it

Abstract: The effect on memory processes of modulation of 5-HT_1A receptor subtype was investigated in the mouse passive avoidance test. The administration of 5-HT_1A-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-HT_1A-receptor agonists 8-OH-DPAT ((ｱ)-8-hydroxy-dipropylaminotetralin) and 5-CT (5-carboxamidotryptamine) dose-dependently prevented the amnesia induced by 5-HT_1A antagonists, scopolamine, dicyclomine and exposure to an hypoxic environment. The antiamnesic effect exerted by 5-HT_1A-receptor agonists was comparable to that produced by the nootropic drug piracetam and cholinesterase inhibitor physostigmine. At effective doses, neither 5-HT_1A-receptor agonists nor 5-HT_1A-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-HT_1A-receptors appears to play an important role in the regulation of cognitive processes.

Keywords: Learning, Memory, 5-HT_1A-receptor, Amnesia, Central serotoninergic system