Central relaxin-3 receptor (RXFP3) activation reduces elevated, but not basal, anxiety-like behaviour in C57BL/6J mice

Zhang, Carry, Chua, Berenice E., Yang, Annie, Shabanpoor, Fazel, Hossain, Mohammad Akhter, Wade, John D., Rosengren, K. Johan, Smith, Craig M. and Gundlach A.L. (2015) Central relaxin-3 receptor (RXFP3) activation reduces elevated, but not basal, anxiety-like behaviour in C57BL/6J mice. Behavioural Brain Research, 292 125-132. doi:10.1016/j.bbr.2015.06.010

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Author Zhang, Carry
Chua, Berenice E.
Yang, Annie
Shabanpoor, Fazel
Hossain, Mohammad Akhter
Wade, John D.
Rosengren, K. Johan
Smith, Craig M.
Gundlach A.L.
Title Central relaxin-3 receptor (RXFP3) activation reduces elevated, but not basal, anxiety-like behaviour in C57BL/6J mice
Journal name Behavioural Brain Research   Check publisher's open access policy
ISSN 1872-7549
Publication date 2015-10-01
Sub-type Article (original research)
DOI 10.1016/j.bbr.2015.06.010
Open Access Status File (Author Post-print)
Volume 292
Start page 125
End page 132
Total pages 8
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2016
Language eng
Abstract Anxiety disorders are among the most prevalent neuropsychiatric conditions, but their precise aetiology and underlying pathophysiological processes remain poorly understood. In light of putative anatomical and functional interactions of the relaxin-3/RXFP3 system with anxiety-related neural circuits, we assessed the ability of central administration of the RXFP3 agonist, RXFP3-A2, to alter anxiety-like behaviours in adult C57BL/6J mice. We assessed how RXFP3-A2 altered performance in tests measuring rodent anxiety-like behaviour (large open field (LOF), elevated plus maze (EPM), light/dark (L/D) box, social interaction). We examined effects of RXFP3-A2 on low ‘basal’ anxiety, and on elevated anxiety induced by the anxiogenic benzodiazepine, FG-7142; and explored endogenous relaxin-3/RXFP3 signalling modulation by testing effects of an RXFP3 antagonist, R3(B1-22)R, on these behaviours. Intracerebroventricular (icv) injection of RXFP3-A2 (1 nmol, 15 min pre-test) did not alter anxiety-like behaviour under ‘basal’ conditions in the LOF, EPM or L/D box, but reduced elevated indices of FG-7142-induced (30 mg/kg, ip) anxiety-like behaviour in the L/D box and a single-chamber social interaction test. Furthermore, R3(B1-22)R (4 nmol, icv, 15 min pre-test) increased anxiety-like behaviour in the EPM (reflected by reduced entries into the open arms), but not consistently in the LOF, L/D box or social interaction tests, suggesting endogenous signaling only weakly participates in regulating ‘basal’ anxiety-like behaviour, in line with previous studies of relaxin-3 and RXFP3 gene knockout mice. Overall, these data suggest exogenous RXFP3 agonists can reduce elevated (FG-7142-induced) levels of anxiety in mice; data important for gauging how conserved such effects are, with a view to modelling human pathophysiology and the likely therapeutic potential of RXFP3-targeted drugs.
Keyword Anxiety
Neuropeptide receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
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