title: Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats.
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.
authors.forename: Emilia
authors.initials: E
authors.lastname: Romano
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Ruocco
authors.forename: Paola
authors.initials: P
authors.lastname: Nativio
authors.forename: Enza
authors.initials: E
authors.lastname: Lacivita
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ajmone-Cat
authors.forename: Giampiero
authors.initials: G
authors.lastname: Boatto
authors.forename: Maria
authors.initials: M
authors.lastname: Nieddu
authors.forename: Angela
authors.initials: A
authors.lastname: Tino
authors.forename: Adolfo G
authors.initials: AG
authors.lastname: Sadile
authors.forename: Luisa
authors.initials: L
authors.lastname: Minghetti
authors.forename: Francesca
authors.initials: F
authors.lastname: Passarelli
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
authors.forename: Walter
authors.initials: W
authors.lastname: Adriani
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
chemical_list: C573815:N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide; D010879:Piperazines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor