The adenosine A_2A agonist CGS 21680 reverses the reduction in prepulse inhibition of the acoustic startle response induced by phencyclidine, but not by apomorphine and amphetamine

Abstract.

Systemic administration of the selective adenosine A_2A 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 A_2A 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 A_2A agonists possess antipsychotic-like properties.