Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice
<p>Abstract</p> <p>Background</p> <p>Repeated exposure to methamphetamine (METH) can cause not only neurotoxicity but also addiction. Behavioral sensitization is widely used as an animal model for the study of drug addiction. We previously reported that the μ-opioid rec...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-11-01
|
| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | http://www.jbiomedsci.com/content/18/1/83 |
| _version_ | 1818934781056909312 |
|---|---|
| author | Park Sang Won Shen Xine Tien Lu-Tai Roman Richard Ma Tangeng |
| author_facet | Park Sang Won Shen Xine Tien Lu-Tai Roman Richard Ma Tangeng |
| author_sort | Park Sang Won |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Repeated exposure to methamphetamine (METH) can cause not only neurotoxicity but also addiction. Behavioral sensitization is widely used as an animal model for the study of drug addiction. We previously reported that the μ-opioid receptor knockout mice were resistant to METH-induced behavioral sensitization but the mechanism is unknown.</p> <p>Methods</p> <p>The present study determined whether resistance of the μ-opioid receptor (μ-OR) knockout mice to behavioral sensitization is due to differential expression of the stimulatory G protein α subunit (Gαs) or regulators of G-protein signaling (RGS) coupled to the dopamine D1 receptor. Mice received daily intraperitoneal injections of saline or METH (10 mg/kg) for 7 consecutive days to induce sensitization. On day 11(following 4 abstinent days), mice were either given a test dose of METH (10 mg/kg) for behavioral testing or sacrificed for neurochemical assays without additional METH treatment.</p> <p>Results</p> <p>METH challenge-induced stereotyped behaviors were significantly reduced in the μ-opioid receptor knockout mice when compared with those in wild-type mice. Neurochemical assays indicated that there is a decrease in dopamine D1 receptor ligand binding and an increase in the expression of RGS4 mRNA in the striatum of METH-treated μ-opioid receptor knockout mice but not of METH-treated wild-type mice. METH treatment had no effect on the expression of Gαs and RGS2 mRNA in the striatum of either strain of mice.</p> <p>Conclusions</p> <p>These results indicate that down-regulation of the expression of the dopamine D1 receptor and up-regulation of RGS4 mRNA expression in the striatum may contribute to the reduced response to METH-induced stereotypy behavior in μ-opioid receptor knockout mice. Our results highlight the interactions of the μ-opioid receptor system to METH-induced behavioral responses by influencing the expression of RGS of dopamine D1 receptors.</p> |
| first_indexed | 2024-12-20T05:09:43Z |
| format | Article |
| id | doaj.art-d5db337f6d264c1cb9d63e172ee636e9 |
| institution | Directory Open Access Journal |
| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-12-20T05:09:43Z |
| publishDate | 2011-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-d5db337f6d264c1cb9d63e172ee636e92022-12-21T19:52:17ZengBMCJournal of Biomedical Science1021-77701423-01272011-11-011818310.1186/1423-0127-18-83Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout micePark Sang WonShen XineTien Lu-TaiRoman RichardMa Tangeng<p>Abstract</p> <p>Background</p> <p>Repeated exposure to methamphetamine (METH) can cause not only neurotoxicity but also addiction. Behavioral sensitization is widely used as an animal model for the study of drug addiction. We previously reported that the μ-opioid receptor knockout mice were resistant to METH-induced behavioral sensitization but the mechanism is unknown.</p> <p>Methods</p> <p>The present study determined whether resistance of the μ-opioid receptor (μ-OR) knockout mice to behavioral sensitization is due to differential expression of the stimulatory G protein α subunit (Gαs) or regulators of G-protein signaling (RGS) coupled to the dopamine D1 receptor. Mice received daily intraperitoneal injections of saline or METH (10 mg/kg) for 7 consecutive days to induce sensitization. On day 11(following 4 abstinent days), mice were either given a test dose of METH (10 mg/kg) for behavioral testing or sacrificed for neurochemical assays without additional METH treatment.</p> <p>Results</p> <p>METH challenge-induced stereotyped behaviors were significantly reduced in the μ-opioid receptor knockout mice when compared with those in wild-type mice. Neurochemical assays indicated that there is a decrease in dopamine D1 receptor ligand binding and an increase in the expression of RGS4 mRNA in the striatum of METH-treated μ-opioid receptor knockout mice but not of METH-treated wild-type mice. METH treatment had no effect on the expression of Gαs and RGS2 mRNA in the striatum of either strain of mice.</p> <p>Conclusions</p> <p>These results indicate that down-regulation of the expression of the dopamine D1 receptor and up-regulation of RGS4 mRNA expression in the striatum may contribute to the reduced response to METH-induced stereotypy behavior in μ-opioid receptor knockout mice. Our results highlight the interactions of the μ-opioid receptor system to METH-induced behavioral responses by influencing the expression of RGS of dopamine D1 receptors.</p>http://www.jbiomedsci.com/content/18/1/83Amphetamineμ-opioid receptoraddictiondopamine receptors |
| spellingShingle | Park Sang Won Shen Xine Tien Lu-Tai Roman Richard Ma Tangeng Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice Journal of Biomedical Science Amphetamine μ-opioid receptor addiction dopamine receptors |
| title | Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice |
| title_full | Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice |
| title_fullStr | Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice |
| title_full_unstemmed | Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice |
| title_short | Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice |
| title_sort | methamphetamine induced changes in the striatal dopamine pathway in μ opioid receptor knockout mice |
| topic | Amphetamine μ-opioid receptor addiction dopamine receptors |
| url | http://www.jbiomedsci.com/content/18/1/83 |
| work_keys_str_mv | AT parksangwon methamphetamineinducedchangesinthestriataldopaminepathwayinmopioidreceptorknockoutmice AT shenxine methamphetamineinducedchangesinthestriataldopaminepathwayinmopioidreceptorknockoutmice AT tienlutai methamphetamineinducedchangesinthestriataldopaminepathwayinmopioidreceptorknockoutmice AT romanrichard methamphetamineinducedchangesinthestriataldopaminepathwayinmopioidreceptorknockoutmice AT matangeng methamphetamineinducedchangesinthestriataldopaminepathwayinmopioidreceptorknockoutmice |