Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats

The serotonin receptor 7 (5-HT7-R) plays important functional roles in learning and memory, in regulation
of mood and circadian rhythmicity. LP 211 is a new selective agonist, belonging to 1-arylpiperazine category.
We report studies aimed to evaluate the modulatory effect of a sub chronic regimen on behavioral/molecular parameters. At low dose [0.25 mg/kg intraperitoneally (i.p.)], LP-211 induced a 6-h anticipated wake up in adult mice
(with no temporal landmark by constant light), acting as nonphotic stimulus for ‘internal clock’ resetting. In standard
12:12-h light/dark cycle, a subchronic effect (5–6!days at 0.25 mg/kg, once per day) was observed: delayed wake up, reduced peak of locomotor activity and no evidence for brain cellular proliferation after ex vivo analysis. Other
studies in rats were aimed to investigate long-term effects of developmental LP-211 administration into adulthood.
Subchronic LP-211 (0.125 mg/kg i.p. once per day during the prepuberal phase) reduced "-glutamate, N-methyl-
#-aspartate receptor 1 and dopamine transporter within the ventral striatum. With LP-211 (0.25 mg/kg i.p. once per
day during the postpuberal phase), clear reductions were observed in the immunoreactivity of serotonin transporter and dopaminergic D2 receptors in the ventral and dorsal
striatum, respectively. Subchronic LP-211 in rats and mice appears to be a suitable tool for studying the role of
5-HT7-R in sleep disorders, emotional/motivational regulations,
attentive processes and executive functions.