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- Title
Sigma<sub>1</sub> receptor upregulation after chronic methamphetamine self-administration in rats: a study with yoked controls.
- Authors
Stefanski, Roman; Justinova, Zuzana; Hayashi, Teruo; Takebayashi, Minoru; Goldberg, Steven R.; Tsung-Ping Su
- Abstract
Rationale. Sigma1 receptors (Sig-1R) are implicated in behavioral sensitization, conditioned place preference, and cellular restructuring induced by psychostimulants. We previously reported that rats which actively self-administered methamphetamine for 5 weeks and were then withdrawn from methamphetamine for 24 h showed downregulation of dopamine D2 autoreceptors (approximately 30%) in the midbrain and this was not seen in rats that passively received injections of methamphetamine or saline at the same time (yoked controls). Involvement of Sig-1R in the self-administration of psychostimulants, however, has never been reported. Objectives. This study examined neuroadaptive changes in Sig-1R in the brains of rats self-administering methamphetamine. Methods. Three groups of rats were tested simultaneously 5 days per week, for 5 weeks (25 daily sessions). Two groups served as yoked controls and passively received an injection of either 0.1 mg/kg methamphetamine or saline (not contingent on responding) each time a response-contingent injection of 0.1 mg/kg methamphetamine was actively self-administered by the first group of rats. Protein and mRNA levels of Sig-1R were then measured by Western and Northern blottings, respectively. Results. There was a marked upregulation of Sig-1R proteins (50%) in the midbrain and altered levels of Sig-1R mRNA in the frontal cortex and hippocampus of rats that learned to actively self-administer methamphetamine, but not in yoked methamphetamine- or saline-control rats. Conclusions. Neuroadaptive increases in Sig-1R seen in this study may contribute to the reinforcing effects of methamphetamine. This upregulation of Sig-1R may be mediated by increased protein kinase A activity due to downregulation of dopamine D2 autoreceptors.
- Subjects
SIGMA particles; AUTORECEPTORS; CELL physiology; RATS; METHAMPHETAMINE
- Publication
Psychopharmacology, 2004, Vol 175, Issue 1, p68
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-004-1779-9