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Sensitization of ethanol‐induced place preference as a result of up‐regulation of type 1 inositol 1,4,5‐trisphosphate receptors in mouse nucleus accumbens
Author(s) -
Kurokawa Kazuhiro,
Mizuno Koji,
Ohkuma Seitaro
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12945
Subject(s) - nucleus accumbens , sensitization , receptor , inositol , chemistry , neuroscience , ethanol , biochemistry , biology
This study involved mice that received 4 days of ethanol (Et OH ) vapor inhalation and then were assessed for type 1 inositol 1,4,5‐trisphosphate receptor ( IP 3 Rs‐1) expression and the development of Et OH ‐induced place preference at various time points in withdrawal. IP 3 R‐1 protein was found to be significantly increased in the nucleus accumbens ( NA cc) of mice immediately after 4‐day Et OH vapor inhalation, while it significantly reduced to the control level during the next 3 days of withdrawal from Et OH inhalation. Et OH (2 g/kg, i.p.)‐induced place preference after 3 days of withdrawal from Et OH vapor inhalation increased dose dependently for 4 days, which was significantly inhibited by 2‐aminophenoxyethane‐borate, an antagonist for IP 3 Rs. Et OH conditioning significantly increased, compared to alcohol‐naïve control mice, both IP 3 R‐1 protein and the release of dopamine in the NA cc of mice after 3 days of withdrawal from Et OH vapor inhaled for 4 days, and this increase of IP 3 R‐1 protein was completely abolished by intracerebroventricular injection of FK 506, an inhibitor for calcineurin. These results indicate that the sensitization of Et OH ‐induced place preference is due to up‐regulated IP 3 R‐1 via calcineurin‐mediated pathway after enhanced release of dopamine in the NA cc on Et OH administration during Et OH conditioning.We revealed signal transduction pathways that may promote sensitization of ethanol (EtOH)‐induced place preference. EtOH facilitated the release of dopamine (DA) in the Nucleus accumbens (NAcc), enhancing calcineurin function via dopamine D1‐like and D2‐like receptor activation, which in turn resulted in increased NFATc4 expression. Increase in NFATc4 may further facilitate transcription factor binding to IP 3 R‐1 promoter domain to stimulate IP 3 R‐1 synthesis. Such increased IP 3 R‐1 elevates intracellular Ca 2+ concentration via facilitated mobilization of Ca 2+ from the intracellular Ca 2+ stores to the cytosol.