Stimulation of 5‐HT7 receptor during adolescence determines its persistent upregulation in adult rat forebrain areas. Issue 11 (14th September 2015)

• Record Type: Journal Article
• Authors: Nativio, Paola; Zoratto, Francesca; Romano, Emilia; Lacivita, Enza; Leopoldo, Marcello; Pascale, Esterina; Passarelli, Francesca; Laviola, Giovanni; Adriani, Walter
• Is Part Of: Synapse. Volume 69:Issue 11(2015:Nov.)
• Page Start: 533
• Page End: 542
• Publication Date: 2015-09-14
• Subjects: Synapses -- Periodicals; 612
• DOI: 10.1002/syn.21846
• Languages: English
• ISSNs: 0887-4476

Abstract

<abstract abstract-type="main"> <title>ABSTRACT </title> <p>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 (<italic>Canese et al., Psycho‐Pharmacol</italic> 2015;<italic>232:75–89</italic>.) 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. <bold>Synapse 69:533–542, 2015</bold>. © 2015 Wiley Periodicals, Inc.</p> </abstract>