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Central relaxin-3 receptor (RXFP3) activation reduces elevated, but not basal, anxiety-like behaviour in C57BL/6J mice
journal contributionposted on 2015-10-01, 00:00 authored by C Zhang, B E Chua, A Yang, F Shabanpoor, M A Hossain, J D Wade, K J Rosengren, Craig SmithCraig Smith, A L Gundlach
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.
JournalBehavioural brain research
Pagination125 - 132
LocationAmsterdam, The Netherlands
Publication classificationC Journal article; C1.1 Refereed article in a scholarly journal
Copyright notice2015, Elsevier B.V.
CategoriesNo categories selected
AnxietyArousalFG-7142Neuropeptide receptorRXFP3Relaxin-3StressAnimalsAnti-Anxiety AgentsBehavior, AnimalCarbolinesMaleMaze LearningMiceMice, Inbred C57BLMice, KnockoutReceptors, G-Protein-CoupledRelaxinScience & TechnologyLife Sciences & BiomedicineBehavioral SciencesNeurosciencesNeurosciences & NeurologyNUCLEUS INCERTUSANIMAL-MODELSNEURONSMOUSERATSINNERVATIONPROJECTIONSDISORDERSCIRCUITS