Related Experiment Video
Updated: Aug 14, 2026
Single Cell Measurement of Dopamine Release with Simultaneous Voltage-clamp and Amperometry
Published on: November 21, 2012
RGS mRNA expression in rat striatum: modulation by dopamine receptors and effects of repeated amphetamine
S A Burchett1, M J Bannon, J G Granneman
1Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA.
Abstract:
Single injections of cocaine, amphetamine, or methamphetamine increased RGS2 mRNA levels in rat striatum by two- to fourfold. The D1 dopamine receptor-selective antagonist SCH-23390 had no effect by itself but strongly attenuated RGS2 mRNA induction by amphetamine. In contrast, the D2 receptor-selective antagonist raclopride induced RGS2 mRNA when administered alone and greatly enhanced stimulation by amphetamine. To examine the effects of repeated amphetamine on RGS2 expression, rats were treated with escalating doses of amphetamine (1.0-7.5 mg/kg) for 4 days, followed by 8 days of multiple daily injections (7.5 mg/kg/2 h x four injections). Twenty hours after the last injection the animals were challenged with amphetamine (7.5 mg/kg) or vehicle and killed 1 h later. In drug-naive animals, acute amphetamine induced the expression of RGS2, 3, and 5 and the immediate early genes c-fos and zif/268. RGS4 mRNA levels were not affected. Prior repeated treatment with amphetamine strongly suppressed induction of immediate early genes and RGS5 to a challenge dose of amphetamine. In sharp contrast, prior exposure to amphetamine did not reduce the induction of RGS2 and RGS3 mRNAs to a challenge dose of amphetamine, indicating that control of these genes is resistant to amphetamine-induced tolerance. These data establish a role for dopamine receptors in the regulation of RGS2 expression and suggest that RGS2 and 3 might mediate some aspects of amphetamine-induced tolerance.
Insights
Repeated amphetamine use alters dopamine receptor regulation of RGS2 and RGS3 gene expression in rats. This suggests these genes may play a role in developing tolerance to amphetamine effects.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Regulator of G protein signaling (RGS) proteins modulate G protein-coupled receptor activity.
- Dopamine receptors are crucial in mediating the effects of psychostimulants like amphetamine.
- Understanding gene expression changes is key to deciphering drug-induced neuroadaptations.
Purpose of the Study:
- To investigate the role of dopamine receptors in regulating RGS2 mRNA expression following acute and repeated amphetamine administration.
- To determine if amphetamine-induced changes in RGS2 and RGS3 mRNA expression are subject to tolerance.
Main Methods:
- Rats were administered single or repeated doses of amphetamine and dopamine receptor antagonists.
- Quantitative real-time PCR was used to measure RGS2, RGS3, RGS5, RGS4, c-fos, and zif/268 mRNA levels in the striatum.
- Tolerance was assessed by challenging pre-treated rats with amphetamine.
Main Results:
- Acute amphetamine, cocaine, and methamphetamine increased striatal RGS2 mRNA levels.
- D1 and D2 dopamine receptor antagonists differentially modulated amphetamine-induced RGS2 mRNA induction.
- Repeated amphetamine administration induced tolerance to the effects on immediate early genes and RGS5, but not RGS2 and RGS3.
Conclusions:
- Dopamine receptors play a significant role in regulating RGS2 expression in the rat striatum.
- RGS2 and RGS3 mRNA induction by amphetamine is resistant to tolerance, suggesting a role in mediating aspects of amphetamine's effects.
- These findings highlight the differential regulation of RGS gene families in response to psychostimulant exposure.
