Developmental expression and serotonergic regulation of relaxin 3/INSL7 in the nucleus incertus of rat brain

Miyamoto, Yasumasa; Watanabe, Yoshihisa; Tanaka, Masaki

doi:10.1016/j.regpep.2007.08.010

Cited by 43 publications

(49 citation statements)

References 17 publications

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“…Because serotonin (5-hydroxytryptamine ) has well established roles in cognitive, emotional, and behavioral control (reviewed in Cools et al, 2008) and the NI is located close to the dorsal raphe, a region enriched in 5-HT neurons, studies were carried out on the effects of 5-HT on relaxin-3 expression (Miyamoto et al, 2008); most relaxin-3-containing neurons of the NI were found to coexpress 5-HT 1A receptors. Inhibition of 5-HT synthesis for 3 days increased relaxin-3 mRNA in the NI.…”

Section: Relaxin Family Peptide Receptorsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Halls¹,

Bathgate²,

Sutton³

et al. 2015

Pharmacol Rev

117

118

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Section: Relaxin Family Peptide Receptorsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Halls¹,

Bathgate²,

Sutton³

et al. 2015

Pharmacol Rev

117

118

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“…In addition, pharmacological depletion of 5-HT alters the levels of relaxin-3 mRNA in nucleus incertus neurons, presumably via 5-HT-1A receptors expressed by these cells or their inputs (Miyamoto et al, 2008).…”

Section: Implications For Understanding Medial Septum Functionmentioning

confidence: 99%

Distribution and targets of the relaxin‐3 innervation of the septal area in the rat

Olucha-Bordonau¹,

Otero-García²,

Sánchez-Pérez³

et al. 2012

J of Comparative Neurology

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Neural tracing studies have revealed that the rat medial and lateral septum are targeted by ascending projections from the nucleus incertus, a population of tegmental GABA neurons. These neurons express the relaxin‐family peptide, relaxin‐3, and pharmacological modulation of relaxin‐3 receptors in medial septum alters hippocampal theta rhythm and spatial memory. In an effort to better understand the basis of these interactions, we have characterized the distribution of relaxin‐3 fibers/terminals in relation to different septal neuron populations identified using established protein markers. Dense relaxin‐3 fiber plexuses were observed in regions of medial septum containing hippocampal‐projecting choline acetyltransferase (ChAT)‐, neuronal nitric oxide synthase (nNOS)‐, and parvalbumin (PV)‐positive neurons. In lateral septum (LS), relaxin‐3 fibers were concentrated in the ventrolateral nucleus of rostral LS and the ventral nucleus of caudal LS, with sparse labeling in the dorsolateral and medial nuclei of rostral LS, dorsal nucleus of caudal LS, and ventral portion nuclei. Relaxin‐3 fibers were also observed in the septofimbrial and triangular septal nuclei. In the medial septum, we observed relaxin‐3‐immunoreactive contacts with ChAT‐, PV‐, and glutamate decarboxylase‐67‐positive neurons that projected to hippocampus, and contacts between relaxin‐3 terminals and calbindin‐ and calretinin‐positive neurons. Relaxin‐3 colocalized with synaptophysin in nerve terminals in all septal areas, and ultrastructural analysis revealed these terminals were symmetrical and contacted spines, somata, dendritic shafts, and occasionally other axonal terminals. These data predict that this GABA/peptidergic projection modulates septohippocampal activity and hippocampal theta rhythm related to exploratory navigation, defensive and ingestive behaviors, and responses to neurogenic stressors. J. Comp. Neurol. 520:1903–1939, 2012. © 2011 Wiley Periodicals, Inc.

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“…Experimental 5-HT depletion in rats significantly increased Rln3 mRNA expression in the nucleus incertus [37], a finding suggesting endogenous RLN3 tone may be high in WT mice during METH withdrawal, relative to a complete lack of tone in the KO mice, increasing the potential for observable phenotypic differences. In addition, repeated intermittent METH treatment and subsequent withdrawal is a stressor associated with increased central corticotropin-releasing factor (CRF) expression [1,38,39]; and nucleus incertus RLN3 neurons are activated in response to CRF and stress in rats via CRF 1 receptors [25,26,40].…”

Section: Introductionmentioning

confidence: 98%

Sensitivity to Chronic Methamphetamine Administration and Withdrawal in Mice with Relaxin-3/RXFP3 Deficiency

et al. 2015

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Methamphetamine (METH) is a highly addictive psychostimulant, and cessation of use is associated with reduced monoamine signalling, and increased anxiety/depressive states. Neurons expressing the neuropeptide, relaxin-3 (RLN3), and its cognate receptor, RXFP3, constitute a putative 'ascending arousal system', which shares neuroanatomical and functional similarities with serotonin (5-HT)/dorsal raphe and noradrenaline (NA)/locus coeruleus monoamine systems. In light of possible synergistic roles of RLN3 and 5-HT/NA, endogenous RLN3/RXFP3 signalling may compensate for the temporary reduction in monoamine signalling associated with chronic METH withdrawal, which could alter the profile of 'behavioural despair', bodyweight reductions, and increases in anhedonia and anxiety-like behaviours observed following chronic METH administration. In studies to test this theory, Rln3 and Rxfp3 knockout (KO) mice and their wildtype (WT) littermates were injected once daily with saline or escalating doses of METH (2 mg/kg, i.p. on day 1, 4 mg/kg, i.p. on day 2 and 6 mg/kg, i.p. on day 3-10). WT and Rln3 and Rxfp3 KO mice displayed an equivalent sensitivity to behavioural despair (Porsolt swim) during the 2-day METH withdrawal and similar bodyweight reductions on day 3 of METH treatment. Furthermore, during a 3-week period after the cessation of chronic METH exposure, Rln3 KO, Rxfp3 KO and corresponding WT mice displayed similar behavioural responses in paradigms that measured anxiety (light/dark box, elevated plus maze), anhedonia (saccharin preference), and social interaction. These findings indicate that a whole-of-life deficiency in endogenous RLN3/RXFP3 signalling does not markedly alter behavioural sensitivity to chronic METH treatment or withdrawal, but leave open the possibility of a more significant interaction with global or localised manipulations of this peptide system in the adult brain.

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Developmental expression and serotonergic regulation of relaxin 3/INSL7 in the nucleus incertus of rat brain

Cited by 43 publications

References 17 publications

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Distribution and targets of the relaxin‐3 innervation of the septal area in the rat

Sensitivity to Chronic Methamphetamine Administration and Withdrawal in Mice with Relaxin-3/RXFP3 Deficiency

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