Chronic alcohol intake produces multiple neuroadaptive changes, including up- and down-regulation of neuro
peptides and
receptors. There are widespread projections of
relaxin-3 containing neurons to, and abundant
relaxin family peptide 3
receptor (RXFP3) expression within, brain regions involved in modulating alcohol intake. Recently we demonstrated the involvement of
relaxin-3/RXFP3 signalling in alcohol-seeking in rats; therefore in this study we examined whether
relaxin-3 and/or RXFP3 expression were altered by chronic alcohol intake in alcohol-preferring iP rats.
4 id="absSec_2">Methods4>
Expression of relaxin-3 mRNA in the hindbrain nucleus incertus and RXFP3 radioligand binding levels in discrete forebrain regions were investigated following voluntary intake of alcohol or sucrose for 12 weeks, with a 2 day washout, using quantitative in situ hybridisation histochemistry and in vitro receptor autoradiography, respectively, in cohorts of adult, male iP rats.
4 id="absSec_3">Results4>
Levels of relaxin-3 mRNA in the hindbrain nucleus incertus were positively correlated with the level of intake of both alcohol (r(12) = 0.59, p = 0.03) and sucrose (r(7) = 0.70, p = 0.04) in iP rats. Dense binding of the RXFP3-selective radioligand, [125]-R3/I5, was detected in hypothalamic and extrahypothalamic sites, but no significant changes in the density of RXFP3 were observed in the brain regions quantified following chronic sucrose or ethanol intake.
4 id="absSec_4">Conclusions4>
Our findings suggest high endogenous relaxin-3 expression may be associated with higher intake of rewarding substances, rather than its expression being regulated in response to their intake, consistent with an active role for the relaxin-3/RXFP3 system in modulating ingestive and alcohol-related behaviours.
