Relaxin-3 mRNA levels in nucleus incertus correlate with alcohol and sucrose intake in rats.
BACKGROUND
Chronic alcohol intake produces multiple neuroadaptive changes, including up- and down-regulation of neuropeptides 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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
P J
PJ
Ryan
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
E V
EV
Krstew
Drug Discovery Biology, Monash Institute of Pharmaceutical Science, Parkville, Victoria, Australia; Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
M
M
Sarwar
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria, Australia.
A L
AL
Gundlach
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: andrew.lawrence@florey.edu.au.
A J
AJ
Lawrence
D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology; D000818:Animals; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics* / Q000378:metabolism; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology
D012333:RNA, Messenger; C577472:RXFP3 protein, rat; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D013395:Sucrose
Alcohol; Neuropeptides; Nucleus incertus; RXFP3; Relaxin-3; mRNA