Activation of 5-HT7 receptor by administration of its selective agonist, LP-211, modifies explorative-curiosity behavior in rats in two paradigms which differ in visuospatial parameters

Aims: The serotonin 7 receptor (5-HT7R) subtype, coded by Htr7 gene, is broadly expressed in the central nervous system (CNS) with clear involvement in behavioral functions such as learning/memory, regulation of mood, and circadian rhythms. In this study, we assessed effects of 5-HT7R stimulation by administration of its selective agonist, LP-211 (0.25 mg/kg i.p.), in adult Wistar-Han rats. Methods: We used two different explorative-curiosity tests. Drug was administered either before one side-chamber familiarization (CF/V group) or immediately after it, to act on consolidation of familiarization (V/CF group). Results: Exp. 1 for novelty seeking in black/white boxes (BWB), with door opening after 5 minutes in the familiar chamber, showed that (i) time spent in the novel environment (significantly higher than in familiar chamber for controls) is enhanced in V/CF group (potentiated recognition for a “visual” consolidation) and not different in CF/V group; (ii) activity and chamber transitions, made by CF/V rats, are significantly higher than for other groups (interference on recognition for a “spatial” acquisition). Exp. 2 for novelty preference in D- vs L-shaped chambers (D/L), with start from neutral center, gave different results: (i) time spent in the novel environment by CF/V group is significantly higher than other groups (potentiated “cognitive” acquisition); (ii) chamber transitions made by V/CF group are significantly higher than other groups (potentiated “emotional” consolidation). Conclusion: These apparently conflicting results may reflect LP-211 effects on visual vs spatial memory (D/L apparatus has more pronounced hippocampal components than BWB). However, further experiments are needed to analyze more in depth the mechanisms involved.