The adenosine A2A agonist CGS 21680 reverses the reduction in prepulse inhibition of the acoustic startle response induced by phencyclidine, but not by apomorphine and amphetamine.
Systemic administration of the selective adenosine A2A agonist CGS 21680, at the highest dose tested (0.5 mg/kg), selectively reversed the reduction in prepulse inhibition (PPI) of the acoustic startle response induced by the NMDA antagonist phencyclidine (PCP), but not by the dopaminergic agonists apomorphine and amphetamine. CGS 21680 by itself was without effect on PPI, but did reduce the amplitude of the startle response. PCP also reduced startle amplitude, but there was no additive or synergistic effect between PCP and CGS 21680 on the startle response. CGS 21680 (0.5 mg/kg) blocked the locomotor activating effect of amphetamine, but this may have been secondary to a reduction in spontaneous locomotion induced by this compound. Taken together, these results indicate that stimulation of adenosine A2A receptors produce no consequence on dopamine agonist-induced disruption in PPI, but regulate the inhibitory effect of NMDA receptor blockade on PPI. This finding raises the possibility that adenosine A2A agonists possess antipsychotic-like properties.
Sills
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TL
Centre for Addiction and Mental Health, Clarke Division, Institute of Psychiatry, Toronto, Canada. terrence@psych.toronto.edu
Azampanah
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Fletcher
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PJ
D000161:Acoustic Stimulation; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006213:Hallucinogens / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D013216:Reflex, Startle / Q000187:drug effects*
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D006213:Hallucinogens; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000661:Amphetamine; D010622:Phencyclidine; D000241:Adenosine; D001058:Apomorphine