Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats
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Emilia Romano
Abstract
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 subchronic 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 l-glutamate, N-methyl-d-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.
Acknowledgments
We acknowledge ERA-net ‘NeuroGenMRI’ and Under-40 ‘ADHD-sythe’ (local units led by EL and LAR) from the Italian Ministry of Health, both projects coordinated by WA as principal investigator. We warmly thank Nicole Ebert (Germany), Gitte Borges (Belgium) and Francesca Zoratto (Italy) for precious help with the experiments described in Boxes 1 and 2.
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Articles in the same Issue
- Frontmatter
- Guest Editorial
- Special issue: potential therapeutic targets involving 5-HT6 and 5-HT7 receptors
- Reviews
- Serotonergic 5-HT7 receptors and cognition
- Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative
- Molecular imaging of the serotonin 5-HT7 receptors: from autoradiography to positron emission tomography
- The procognitive effects of 5-HT6 receptor ligands in animal models of schizophrenia
- Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats
- Selective agonists for serotonin 7 (5-HT7) receptor and their applications in preclinical models: an overview
- 5-HT6 receptor antagonists as treatment for age-related cognitive decline
- The role of serotonin 5-HT7 receptor in regulating sleep and wakefulness
- Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders
- Computational approaches to the design of novel 5-HT6 R ligands
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Special issue: potential therapeutic targets involving 5-HT6 and 5-HT7 receptors
- Reviews
- Serotonergic 5-HT7 receptors and cognition
- Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative
- Molecular imaging of the serotonin 5-HT7 receptors: from autoradiography to positron emission tomography
- The procognitive effects of 5-HT6 receptor ligands in animal models of schizophrenia
- Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats
- Selective agonists for serotonin 7 (5-HT7) receptor and their applications in preclinical models: an overview
- 5-HT6 receptor antagonists as treatment for age-related cognitive decline
- The role of serotonin 5-HT7 receptor in regulating sleep and wakefulness
- Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders
- Computational approaches to the design of novel 5-HT6 R ligands