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Updated: Jun 12, 2026

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System
Published on: April 25, 2012
F15599, a preferential post-synaptic 5-HT1A receptor agonist: activity in models of cognition in comparison with
Ronan Depoortère1, Agnès L Auclair, Laurent Bardin
1Neurobiology 2 Division, Centre de Recherche Pierre Fabre, 17, avenue Jean Moulin, 81106 Castres, France. ronan.depoortere@pierre-fabre.com
Abstract:
We assessed the activity of F15599, a selective and high efficacy 5-HT(1A) agonist that preferentially activates post- versus pre-synaptic receptors, in rat cognition/memory models. F15599 (0.16 mg/kg i.p.) partially alleviated detrimental effects of phencyclidine on working and reference memory deficit in a hole-board model. It also attenuated phencyclidine-induced deficit of cognitive flexibility in a reversal learning task, without effects of its own. F13714 (0.04 mg/kg) a chemical congener of F15599, and 8-OH-DPAT (0.01 or 0.16), were inactive against these phencyclidine-induced deficits, and/or even worsened basal performances. F15599 (0.04-2.5) was less disruptive than F13714 (0.005-0.16) or 8-OH-DPAT (0.01-0.63), on basal performance in models of attention (5-choice serial reaction time task) and working memory (delayed non-matching to position). Finally, unlike either comparator, F15599 reduced PPI with modest potency and only partially. To conclude, F15599, in models of memory/cognition, has a more favourable profile than F13714 and 8-OH-DPAT. This suggests that preferential activation of post-synaptic 5-HT(1A) receptors could prove useful in pathologies characterized by cognitive/memory deficiencies, such as schizophrenia and depression.
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