The adenosine A1 receptor agonist N6-cyclopentyladenosine blocks the disruptive effect of phencyclidine on prepulse inhibition of the acoustic startle response in the rat.
Systemic administration of the NMDA receptor antagonist phencyclidine (PCP; 4 mg/kg) produced a profound reduction in prepulse inhibition of the acoustic startle response in rats. Pre-treatment with the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) blocked (0.5 mg/kg) or attenuated (0.1 and 0.2 mg/kg) the disruptive effect of PCP on prepulse inhibition. These findings suggest that adenosine may regulate the inhibitory effect of NMDA receptor blockade on prepulse inhibition, and raise the possibility that adenosine may be a potentially useful target for anti-psychotic medication. Further, 0.5 mg/kg CPA by itself was without effect on prepulse inhibition but did decrease startle amplitude, raising the possibility that adenosine, acting via A1 receptors, may be a component of the neurochemical substrate that modulates the acoustic startle response.
Sills
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Centre for Addiction and Mental Health, Clarke Division, Clarke Institute of Psychiatry, Toronto, Canada. terrence@psych.toronto.edu
Azampanah
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Fletcher
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D000161:Acoustic Stimulation; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013216:Reflex, Startle / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D058906:Purinergic P1 Receptor Agonists; D016194:Receptors, N-Methyl-D-Aspartate; C048599:N(6)-cyclopentyladenosine; D010622:Phencyclidine; D000241:Adenosine