Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats

Romano, Emilia; Ruocco, L; Nativio, Paola; Lacivita, Enza; Ajmone‐Cat, Maria Antonietta; Boatto, Gianpiero; Nieddu, Maria; Tino, Angela; Sadile, A.G.; Minghetti, Luisa; Passarelli, Francesca; Leopoldo, Marcello; Laviola, Giovanni; Adriani, Walter

doi:10.1515/revneuro-2014-0007

Cited by 17 publications

(26 citation statements)

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“…In the human brain, the presence of 5-HT 7 receptors was confirmed by post-mortem studies on adult subjects (age range 22–73 years; Martin-Cora and Pazos, 2004; Varnäs et al, 2004). Moreover, systemic administration of 5-HT 7 receptor agonists affected body temperature (Naumenko et al, 2011) and circadian rhythms (Adriani et al, 2012; Monti et al, 2014; Romano et al, 2014) in adult animals and improved learning in young adults (Eriksson et al, 2008; Freret et al, 2014). All these data indicate that 5-HT 7 receptor-mediated effects are still present at adult age and exert an important control on various physiological functions.…”

Section: Characterization Of 5-ht7 Receptorsmentioning

confidence: 99%

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

Ciranna

Catania

2014

Front. Cell. Neurosci.

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Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD.

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Section: Characterization Of 5-ht7 Receptorsmentioning

confidence: 99%

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

Ciranna

Catania

2014

Front. Cell. Neurosci.

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“…In the CNS the receptor is expressed in the diencephalon, forebrain and in the Purkinje neurons of the cerebellum (for reviews see Matthys et al, 2011; Gellynck et al, 2013). The wide distribution of 5-HT7R in the brain reflects the numerous functions in which this receptor is implicated, such as circadian rhythms, sleep-wake cycle, thermoregulation (Leopoldo et al, 2011; Adriani et al, 2012; Monti et al, 2014; Romano et al, 2014) and nociception (Garcia et al, 2011), but also cognitive functions such as learning and memory processing (Roberts and Hedlund, 2012; Freret et al, 2014; Meneses, 2014). Importantly, the putative involvement of 5-HT7R in many neuropathological processes such as anxiety, schizophrenia, epilepsy, migraine, impulsivity and depression, cognitive and mood disturbances (Hedlund, 2009; Cates et al, 2013; Gellynck et al, 2013), makes it a potential target for new therapeutic applications.…”

Section: The Serotonin Receptormentioning

confidence: 99%

The serotonin receptor 7 and the structural plasticity of brain circuits

Volpicelli

Speranza

Porzio

et al. 2014

Front. Behav. Neurosci.

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Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R) in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration.

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“…This profile suggests an increase of tonic DA release. Such a hypothesis is supported by reduction found for D2 receptor levels, which are known to act as auto‐receptors (Romano et al, ).…”

Section: Discussionmentioning

confidence: 89%

“…However, it appeared not to be involved in these network changes. For the sake of neurochemistry, we may add to our picture the notion of a decreased level of D2 receptors in the dorsal and of SERT in the ventral striata (Romano et al, ). Other changes (but with longer LP‐211 treatment at a low dose) include decreased glutamate and NMDA‐R1 levels in the accumbens (Ruocco et al, ).…”

Section: Discussionmentioning

confidence: 95%

“…The last serotonin receptor subtype to be identified, the 5‐HT7‐R (Hoyer et al, ), shows its greatest abundance in the thalamus, hypothalamus (including the suprachiasmatic nucleus), dorsal raphe and hippocampus, whereas lower levels are reported for cerebral cortex, striatum and amygdala (Cifariello et al, ; Leo et al, ; Leopoldo et al, ; Varnäs et al, ). This distribution is highly correlated with its putative function, in the regulation of circadian rhythms and REM sleep, thermoregulation, nociception, sensation‐seeking behavior, impulsivity as well as learning and memory (Matthys et al, ; Romano et al, ). Dysfunction of the brain 5‐HT7‐R system may play a role in pathologies like obsessive–compulsive disorder, anxiety, depression, schizophrenia, epilepsy, migraine; it has also been recently implicated in neuroendocrine regulation (Papageorgiou and Denef, ; Siddiqui et al, ) and neurogenic inflammation (Lieb et al, ; Mahé et al, ).…”

Section: Introductionmentioning

confidence: 99%

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

Nativio

Zoratto

Romano

et al. 2015

Synapse

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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.

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Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats

Cited by 17 publications

References 50 publications

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

The serotonin receptor 7 and the structural plasticity of brain circuits

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

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