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Essential role for RGS9 in opiate action
Venetia Zachariou1, Dan Georgescu, Nick Sanchez
1Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Summary
Regulators of G protein signaling (RGS) proteins, like RGS9, modulate opiate effects. Reduced RGS9 levels enhance morphine
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Regulators of G protein signaling (RGS) proteins modulate G protein-coupled receptor (GPCR) signaling.
- RGS9-2, a splice variant of RGS9, is highly expressed in brain regions mediating opiate effects.
- Opiate receptors are GPCRs involved in reward, analgesia, addiction, and dependence.
Purpose of the Study:
- To investigate the role of RGS9 in mediating the acute and chronic effects of morphine.
- To determine how morphine administration affects RGS9-2 expression in the brain.
Main Methods:
- Quantitative analysis of RGS9-2 expression in response to acute and chronic morphine administration.
- Behavioral analysis of morphine responses in RGS9 knockout mice.
Main Results:
- Acute morphine increased RGS9-2 expression, while chronic morphine decreased it.
- Mice lacking RGS9 exhibited heightened behavioral responses to morphine, including increased reward and analgesia, delayed tolerance, and exacerbated dependence and withdrawal.
Conclusions:
- RGS9 acts as a negative modulator of opiate action in vivo.
- Changes in RGS9 levels during chronic morphine exposure contribute to behavioral and neural plasticity associated with addiction and dependence.