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Sensitivity to chronic methamphetamine administration and withdrawal in mice with relaxin-3/RXFP3 deficiency

Haidar, Mouna, Lam, Monica, Chua, Berenice E., Smith, Craig M. and Gundlach, Andrew L. 2016, Sensitivity to chronic methamphetamine administration and withdrawal in mice with relaxin-3/RXFP3 deficiency, Neurochemical research, vol. 41, no. 3, pp. 481-491, doi: 10.1007/s11064-015-1621-2.

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Title Sensitivity to chronic methamphetamine administration and withdrawal in mice with relaxin-3/RXFP3 deficiency
Author(s) Haidar, Mouna
Lam, Monica
Chua, Berenice E.
Smith, Craig M.
Gundlach, Andrew L.
Journal name Neurochemical research
Volume number 41
Issue number 3
Start page 481
End page 491
Total pages 11
Publisher Springer
Place of publication New York, N.Y.
Publication date 2016-03
ISSN 0364-3190
1573-6903
Keyword(s) relaxin-3
Rxfp3
knockout mice
methamphetamine
monoamines
arousal
Summary Methamphetamine (METH) is a highly addictivepsychostimulant, and cessation of use is associatedwith reduced monoamine signalling, and increased anxiety/depressive states. Neurons expressing the neuropeptide,relaxin-3 (RLN3), and its cognate receptor, RXFP3, constitutea putative ‘ascending arousal system’, which sharesneuroanatomical and functional similarities with serotonin(5-HT)/dorsal raphe and noradrenaline (NA)/locus coeruleusmonoamine systems. In light of possible synergisticroles of RLN3 and 5-HT/NA, endogenous RLN3/RXFP3signalling may compensate for the temporary reduction inmonoamine signalling associated with chronic METHwithdrawal, which could alter the profile of ‘behaviouraldespair’, bodyweight reductions, and increases in anhedoniaand anxiety-like behaviours observed following chronicMETH administration. In studies to test this theory, Rln3and Rxfp3 knockout (KO) mice and their wildtype (WT)littermates were injected once daily with saline or escalatingdoses of METH (2 mg/kg, i.p. on day 1, 4 mg/kg,i.p. on day 2 and 6 mg/kg, i.p. on day 3–10). WT and Rln3and Rxfp3 KO mice displayed an equivalent sensitivity tobehavioural despair (Porsolt swim) during the 2-dayMETH withdrawal and similar bodyweight reductions onday 3 of METH treatment. Furthermore, during a 3-weekperiod after the cessation of chronic METH exposure, Rln3KO, Rxfp3 KO and corresponding WT mice displayedsimilar behavioural responses in paradigms that measuredanxiety (light/dark box, elevated plus maze), anhedonia(saccharin preference), and social interaction. These findingsindicate that a whole-of-life deficiency in endogenousRLN3/RXFP3 signalling does not markedly alter behaviouralsensitivity to chronic METH treatment or withdrawal,but leave open the possibility of a more significantinteraction with global or localised manipulations of thispeptide system in the adult brain.
Language eng
DOI 10.1007/s11064-015-1621-2
Field of Research 111502 Clinical Pharmacology and Therapeutics
Socio Economic Objective 0 Not Applicable
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Springer Science + Business Media New York
Persistent URL http://hdl.handle.net/10536/DRO/DU:30091748

Document type: Journal Article
Collection: School of Medicine
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