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.

Stimulation of 5-HT7 receptor during adolescence determines its persistent upregulation in adult rat forebrain areas / Nativio, Paola; Zoratto, Francesca; Romano, Emilia; Lacivita, Enza; Leopoldo, Marcello; Pascale, Esterina; Passarelli, Francesca; Laviola, Giovanni; Adriani, Walter. - In: SYNAPSE. - ISSN 0887-4476. - STAMPA. - 69:11(2015), pp. 533-542. [10.1002/syn.21846]

Stimulation of 5-HT7 receptor during adolescence determines its persistent upregulation in adult rat forebrain areas

NATIVIO, PAOLA;PASCALE, ESTERINA;PASSARELLI, Francesca;
2015

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.
2015
D2 receptor; DAT; Dorsal/ventral striata; Emotional; Immunohistochemisty; Motivational and cognitive modulation; Network connectivity; Piriform cortex; SERT; Animals; Immunohistochemistry; Male; Neural Pathways; Piperazines; Prosencephalon; Rats, Wistar; Receptors, Serotonin; Serotonin Receptor Agonists; Up-Regulation; Cellular and Molecular Neuroscience
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Stimulation of 5-HT7 receptor during adolescence determines its persistent upregulation in adult rat forebrain areas / Nativio, Paola; Zoratto, Francesca; Romano, Emilia; Lacivita, Enza; Leopoldo, Marcello; Pascale, Esterina; Passarelli, Francesca; Laviola, Giovanni; Adriani, Walter. - In: SYNAPSE. - ISSN 0887-4476. - STAMPA. - 69:11(2015), pp. 533-542. [10.1002/syn.21846]
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