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Change in down‐stream signaling of striatal dopaminergic transmission in methamphetamine‐sensitized mice
Author(s) -
Tien LuTai,
Lee YihJing
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb456
Subject(s) - methamphetamine , dopaminergic , sensitization , saline , dopamine , behavioral sensitization , pharmacology , phosphorylation , medicine , phosphoprotein , endocrinology , chemistry , psychology , nucleus accumbens , neuroscience , biochemistry
Repeated administration of methamphetamine has been known to produce a progressively enhanced and persistent behavioral response in rodents, a phenomenon called “behavioral sensitization”. The present study was designed to investigate the changes in down‐stream signaling of dopaminergic system after administration of methamphetamine. Mice were injected with saline or methamphetamine (1 mg/kg, i.p.) once a day for 7 consecutive days. The expression of behavioral sensitization was tested on day 11 (after 4‐day drug abstinence). The locomotor activity was increased in methamphetamine treated mice than that of the saline treated group. On day 11, methamphetamine‐induced locomotor activity was significantly higher than those of the same group of mice on day 1, suggesting the development of behavioral sensitization. Repeated injection of saline had no effect on locomotor activity in mice on any given day. The striatal neurons of saline and methamphetamine treated mice were collected after locomotor activity monitoring for DARPP‐32 (a dopamine and cAMP‐regulated phosphoprotein of Mr32) and phosphorylation of DARPP‐32 assay. Two sites of phosphorylation on DARPP‐32: p‐DARPP‐32 (Thr34) and p‐DARPP‐32 (Thr75) were detected. There were no significant differences in the protein levels of DARPP‐32, p‐DARPP‐32 (Thr34) and p‐DARPP‐32 (Thr75) between the saline and methamphetamine treated mice on day 1. The level of p‐DARPP‐32 (Thr75), but not DARPP‐32 and p‐DARPP‐32 (Thr34), is significantly higher than that of the saline treated mice on day 11. These data showed that phosphorylation of DARPP‐32 especially on Thr75 may be related to the expression of methamphetamine‐induced sensitization. (This study is supported by a grant NHRI‐EX99‐9815NC from National Health Research Institutes of Taiwan)