title: Stimulation of 5-HT7 receptor during adolescence determines its persistent upregulation in adult rat forebrain areas.
abstract: Brain serotonin 7 (5-HT7) receptors play an important functional role in learning and memory, in regulation of mood and motivation, and for circadian rhythms. Recently, we have studied the modulatory effects of a developmental exposure (under subchronic regimen) in rats with LP-211, a brain-penetrant and selective 5-HT7 receptor agonist. We aimed at further deciphering long-term sequelae into adulthood. LP-211 (0.250 mg/kg i.p., once/day) was administered for 5 days during the adolescent phase (postnatal days 43-45 to 47-49). When adult (postnatal days >70), forebrain areas were obtained for ex vivo immunohistochemistry, whose results prompted us to reconsider the brain connectivity maps presented in our previous study (Canese et al., Psycho-Pharmacol 2015;232:75-89.) Significant elevation in levels of 5-HT7 receptors were evidenced due to adolescent LP-211 exposure, in dorsal striatum (which also shows an increase of dopaminergic D2 auto-receptors) and-unexpectedly-in piriform cortex, with no changes in ventral striatum. We observed that functional connectivity from a seed on the right hippocampus was more extended than reported, also including the piriform cortex. As a whole, the cortical loop rearranged by adolescent LP-211 exposure consisted in a hippocampus receiving connections from piriform cortex and dorsal striatum, the latter both directly and through functional control over the 'extended amygdala'. Such results represent a starting point to explore neurophysiology of 5-HT7 receptors. Further investigation is warranted to develop therapies for sleep disorders, for impaired emotional and motivational regulation, for attentive and executive deficit. The 5-HT7 agonist LP-211 (0.250 mg/kg i.p., once/day) was administered for 5 days during adolescence (postnatal days 43-45 to 47-49) in rats. When adult (postnatal days >70), a significant elevation in levels of 5-HT7 receptors were evidenced in dorsal striatum and-unexpectedly-in piriform cortex.
authors.affiliation: Departments of Molecular Medicine and of Medical Surgical Sciences and Biotechnology, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Nativio
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore Di Sanità, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zoratto
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore Di Sanità, Rome, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Romano
authors.affiliation: Department of Pharmacy, Università Degli Studi "a. Moro", Bari, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Lacivita
authors.affiliation: Department of Pharmacy, Università Degli Studi "a. Moro", Bari, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
authors.affiliation: Departments of Molecular Medicine and of Medical Surgical Sciences and Biotechnology, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Esterina
authors.initials: E
authors.lastname: Pascale
authors.affiliation: Departments of Molecular Medicine and of Medical Surgical Sciences and Biotechnology, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Passarelli
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore Di Sanità, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore Di Sanità, Rome, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Adriani
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: C573815:N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor
keywords: D2 receptor; DAT; SERT; dorsal/ventral striata; emotional; immunohistochemisty; motivational and cognitive modulation; network connectivity; piriform cortex