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Persistent behavioral sensitization to chronic L-DOPA requires A2A adenosine receptors
Silva Fredduzzi1, Rosario Moratalla, Angela Monopoli
1Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02129, USA.
Summary
Adenosine A(2A) receptors are crucial for sustained behavioral responses to L-DOPA in Parkinson
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Parkinson's disease involves dopamine deficiency, often treated with L-DOPA.
- Chronic L-DOPA can lead to motor complications like dyskinesia.
- Adenosine A(2A) receptors modulate dopamine system function.
Purpose of the Study:
- To determine the role of adenosine A(2A) receptors in adaptive responses to chronic L-DOPA.
- To investigate the impact of A(2A) receptor knockout on L-DOPA-induced behavioral sensitization.
Main Methods:
- Comparison of behavioral sensitization in wild-type and A(2A) receptor knockout mice after 6-hydroxydopamine lesion.
- Assessment of motor responses (rotation, grooming) and striatal dynorphin mRNA levels.
Main Results:
- A(2A) receptor knockout mice showed transient, not persistent, behavioral sensitization to L-DOPA.
- Sensitized grooming was absent in knockout mice.
- L-DOPA-induced normalization of dynorphin mRNA was impaired in knockout mice.
Conclusions:
- Adenosine A(2A) receptors are critical for the development and persistence of L-DOPA-induced behavioral sensitization.
- Inactivating A(2A) receptors may attenuate L-DOPA-induced dyskinesia in Parkinson's disease.