GABAergic involvement in motor effects of an adenosine A(2A) receptor agonist in mice.
Adenosine A(2A) agonists are known to induce catalepsy and inhibit dopamine mediated motor hyperactivity. An antagonistic interaction between adenosine A(2A) and dopamine D(2) receptors is known to regulate GABA-mediated neurotransmission in striatopallidal neurons. Stimulation of adenosine A(2A) and dopamine D(2) receptors has been shown to increase and inhibit GABA release respectively in pallidal GABAergic neurons. However, the role of GABAergic neurotransmission in the motor effects of adenosine A(2A) receptors is not yet known. Therefore in the present study the effect of GABAergic agents on adenosine A(2A) receptor agonist (NECA- or CGS 21680) induced catalepsy and inhibition of amphetamine elicited motor hyperactivity was examined. Pretreatment with GABA, the GABA(A) agonist muscimol or the GABA(B) agonist baclofen potentiated whereas the GABA(A) antagonist bicuculline attenuated NECA- or CGS 21680-induced catalepsy. However, the GABA(B) antagonists phaclophen and delta-aminovaleric acid had no effect. Administration of NECA or CGS 21680 not only reduced spontaneous locomotor activity but also antagonized amphetamine elicited motor hyperactivity. These effects of NECA and CGS 21680 were potentiated by GABA or muscimol and antagonized by bicuculline. These findings provide behavioral evidence for the role of GABA in the motor effects of adenosine A(2A) receptor agonists. Activation of adenosine A(2A) receptors increases GABA release which could reduce dopaminergic tone and induce catalepsy or inhibit amphetamine mediated motor hyperactivity.
Khisti
R T
RT
Department of Pharmaceutical Sciences, Nagpur University Campus, Nagpur 440 010, Maharashtra, India.
Chopde
C T
CT
Abraham
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E
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000661:Amphetamine; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D015259:Dopamine Agents; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2 / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015259:Dopamine Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D005680:gamma-Aminobutyric Acid; D000661:Amphetamine; D000241:Adenosine