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Adenosine A2A receptor knockout mice are partially protected against drug-induced catalepsy
M El Yacoubi1, C Ledent, M Parmentier
1UMR 6036 CNRS, IFRMP 23, UFR de Médecine and Pharmacie, Rouen, France.
Abstract:
Catalepsy assessed using the bar test was measured in both adenosine A2A receptor knockout (A2AR KO) and wild-type (A2AR WT) mice submitted to acute administration of the dopamine D2 receptor antagonist haloperidol (0.5, 2, 4, 6 mg/kg i.p.), the dopamine D1 antagonist SCH 23390 (0.3-3 mg/kg, s.c.), the vesicular monoamine transporter blocker reserpine (3-5 mg/kg, s.c.) or the acetylcholine muscarinic receptor agonist pilocarpine (25-50 mg/kg, i.p.). Except for reserpine, catalepsy scores were significantly lower in A2AR KO mice than in A2AR WT mice following low doses of these cataleptogenic agents. These results suggest that adenosine A2A receptors influence not only dopamine D2 and D1 receptor-mediated neurotransmission but also acetylcholine muscarinic receptor-mediated neurotransmission.
Insights
Adenosine A2A receptors modulate dopamine and acetylcholine pathways. A2A receptor knockout mice showed reduced catalepsy, indicating these receptors influence motor control.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Adenosine A2A receptors are implicated in modulating dopaminergic neurotransmission.
- The precise role of adenosine A2A receptors in other neurotransmitter systems, like cholinergic pathways, remains less understood.
Purpose of the Study:
- To investigate the role of adenosine A2A receptors in catalepsy induced by dopaminergic and cholinergic agents.
- To compare the effects of cataleptogenic drugs in adenosine A2A receptor knockout (A2AR KO) and wild-type (A2AR WT) mice.
Main Methods:
- Catalepsy was assessed using the bar test in A2AR KO and A2AR WT mice.
- Mice were administered haloperidol (D2 antagonist), SCH 23390 (D1 antagonist), reserpine (vesicular monoamine transporter blocker), or pilocarpine (muscarinic agonist).
Main Results:
- A2AR KO mice exhibited significantly lower catalepsy scores compared to A2AR WT mice, except when treated with reserpine.
- This reduction in catalepsy was observed following acute administration of low doses of haloperidol, SCH 23390, and pilocarpine.
Conclusions:
- Adenosine A2A receptors play a significant role in modulating both dopamine D1/D2 receptor-mediated and acetylcholine muscarinic receptor-mediated neurotransmission.
- These findings highlight the broader influence of adenosine A2A receptors on motor control and neurotransmitter systems beyond dopamine.