title: Central relaxin-3 receptor (RXFP3) activation decreases anxiety- and depressive-like behaviours in the rat.
abstract: Relaxin-3 is a recently discovered neuropeptide and the results of earlier anatomical and pharmacological studies suggest it plays a physiological role in modulating functions such as arousal, learning and memory, food intake and neuroendocrine homeostasis. Relaxin-3 is also postulated to modulate affective behaviour, based on high densities of the relaxin-3 G-protein coupled receptor (RXFP3) in brain areas involved in stress and mood/anxiety, including the central amygdala, bed nucleus of the stria terminalis and hypothalamic paraventricular nucleus (PVN); and strong activation of relaxin-3 neurons by stressors, via activation of corticotropin-releasing factor receptor-1 (CRF1). This study assessed the effect of central administration of a newly developed RXFP3-selective agonist, on anxiety- and depressive-like behaviour in rats. Adult, male Sprague-Dawley rats administered 5 μg [R3A(11-24,C15→A)B] (referred to as RXFP3-A2), intracerebroventricularly, demonstrated decreased anxiety-like behaviour in the light-dark box and elevated plus maze, but not in the open field. Notably, in the repeat forced swim test, central RXFP3-A2 administration decreased immobility in rats that had been subjected to the 'stress' of former exposure to the anxiety tests, but not in experimentally naïve rats. These data implicate relaxin-3/RXFP3 signalling in the modulation of effects of acute (anxiety) and cumulative (depression) neurogenic stressors on behaviour; and suggest a potential for RXFP3 agonists as anxiolytic and anti-depressant agents. In addition, our results demonstrate that exposure of adult Sprague-Dawley rats to tests of anxiety-like behaviour (∼10-14 days prior) can significantly increase immobility time in the repeat forced swim test.
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia.
authors: Philip J
authors: PJ
authors: Ryan
authors: Elena
authors: E
authors: Büchler
authors: Fazel
authors: F
authors: Shabanpoor
authors: Mohammed Akhter
authors: MA
authors: Hossain
authors: John D
authors: JD
authors: Wade
authors: Andrew J
authors: AJ
authors: Lawrence
authors: Andrew L
authors: AL
authors: Gundlach
mesh_terms: D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D003863:Depression / Q000517:prevention & control*; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009419:Nerve Tissue Proteins / Q000502:physiology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000502:physiology*; D018000:Receptors, Peptide / Q000819:agonists* / Q000502:physiology*; D012065:Relaxin / Q000502:physiology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; C466742:RLN3 protein, rat; C577472:RXFP3 protein, rat; C583617:RXFP3-a2 peptide; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin