Short communicationEffects of the potential 5-HT7 receptor agonist AS 19 in an autoshaping learning task
Introduction
A growing body of evidence from snails to humans shows that serotonin (5-hydroxytryptamine, 5-HT) input participates in memory formation [6], [7]. It remains unclear if this 5-HT influence is tonic or phasic, involving different 5-HT receptors (for review, see [7]) and/or multiple cell signaling pathways [12]. Actually, compromised serotonergic function may have an important contribution to cognitive decline related to aging, Alzheimer's disease (AD) [1], [2] and schizophrenia. Serotonergic dysfunction represents a potential target for treatment of memory dysfunctions [6], [7], and opens opportunities for the exploration of 5-HT agonists, antagonists, inverse agonists and mix activity ligands (agonists/antagonists). Recent evidence indicates that the 5-HT1A/7 receptor agonist 8-OH-DPAT facilitated memory formation, and such an effect was blocked by the selective 5-HT1A receptor antagonist WAY 100635 and 5-HT7 antagonist SB-269970 [8]. Until recently there were not selective 5-HT7 receptor agonists. Hence, in this work, we aim to re-evaluate further the role of 5-HT7 receptors during memory formation in an autoshaping Pavlovian/instrumental learning task. Herein, post-training administration of the potentially selective 5-HT7 receptor agonist (2S)-(+)-8-(1,3,5-trimethylpyrazolin-4-yl)-2-(dimethylamino) tetralin (AS 19) (binding IC50 = 0.83 nM; Tocris; see Sanin et al. [13] or the selective 5-HT1A (WAY 100635) or 5-HT7 receptor antagonist (SB-269970) [8] were tested. In addition, AS 19 was also evaluated in the pharmacological models of amnesia induced by scopolamine (cholinergic antagonist) and dizocilpine (NMDA antagonist).
Section snippets
Materials and methods
Male Wistar rats (12-week-old) were collectively housed in a temperature- and light-controlled room under a 12:12 h light/dark cycle (light on at 7:00 a.m.) with water and food provided ad libitum for a week. After that period, body weights were reduced to 85% by gradually reducing food intake. The autoshaping test has been previously described (see [7]). Briefly, male Wistar rats (12-week-old) were collectively housed (12/cage) in a temperature controlled animal room (22 ± 11 °C) and on an
Discussion
The major finding of the present work is that the 5-HT7 receptor agonist AS 19 facilitated memory formation and significantly inhibited the amnesic-induced effects of scopolamine or dizocilpine, which is consistent with previous evidence (see below). These data support the notion that serotonergic, glutamatergic, and cholinergic systems interact in cognitively impaired animals [6], [7]. Since a growing interest in 5-HT7 receptors investigation concerning a number of functions and pathologies,
Acknowledgements
Authors thank GlaxoSmithKline for its generous gifts (see drugs section). This work was partially supported by the CONACYT Scholarship 185583 (G.S.P.G.) and Grant 39534-M (A.M.). We thank Sofia Meneses-Goytia for revised language, and Roberto Gonzalez for his expertise and assistance. Finally, authors want to deeply thank the reviewer's comments, which were very useful and their incorporation significantly improved the original version of our manuscript.
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