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Defective motor behavior and neural gene expression in RIIbeta-protein kinase A mutant mice
E P Brandon1, S F Logue, M R Adams
1Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195, USA.
Summary
The RIIbeta subunit of protein kinase A (PKA) is crucial for motor learning and gene regulation in the striatum. Its absence affects experience-dependent behaviors but not acute responses to dopamine drugs.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Dopamine signaling in the striatum modulates motor behavior.
- G-protein-coupled pathways, including cAMP-dependent protein kinase (PKA), are involved.
- The RIIbeta isoform of PKA is highly expressed in the striatum.
Purpose of the Study:
- To investigate the role of the RIIbeta isoform of PKA in motor behavior and neuronal gene expression.
- To determine the necessity of RIIbeta PKA for experience-dependent motor learning and drug responses.
Main Methods:
- Targeted gene disruption of RIIbeta in mice.
- Assessment of locomotor responses to dopaminergic drugs.
- Evaluation of rotarod task performance and amphetamine sensitization.
- Measurement of fos and dynorphin mRNA expression in the striatum.
Main Results:
- RIIbeta knockout mice showed normal acute responses to dopaminergic drugs.
- Mutant mice exhibited deficits in rotarod training and amphetamine sensitization.
- Amphetamine-induced fos expression was absent in mutant mice.
- Basal dynorphin mRNA expression was reduced in the striatum of RIIbeta knockout mice.
Conclusions:
- RIIbeta PKA is essential for motor learning and experience-dependent behaviors.
- RIIbeta PKA plays a critical role in the regulation of neuronal gene expression.
- Acute locomotor effects of dopaminergic drugs are largely independent of RIIbeta PKA.