Modulation of the striato-pallidal pathway by adenosine A2a receptors depends on dopaminergic striatal input

The modulation of the striato-pallidal pathway by presynaptic adenosine A2a and dopamine D2 receptors has gained attention in the study of Parkinson's disease. Here, we analyzed the effect of presynaptic A2a receptors in the spiking activity of globus pallidus (GP) neurons recorded during electrical stimulation of the striato-pallidal pathway, in both sham and ipsilaterally dopamine-denervated rats. We found that intrapallidal blockade of A2a by 100 pMol KF-17383 in sham and lesioned rats did not modify the spiking rate of GP neurons. Local infusion of 100 pMol CGS-21680, an A2a agonist, did not change the spiking rate in sham rats, whereas the same concentration of NMDA strongly increased the firing frequency of all neurons tested. Moreover, in sham rats, local blockade of A2a receptors by 100 pMol KF-17383 suppressed the inhibition evoked by activation of the striato-pallidal pathway, while in dopamine-denervated rats the same dose of KF-17383 did not modify the inhibition. Our results show that the contribution of A2a receptors to the spiking control of GP by the striato-pallidal pathway depends on the state of the dopaminergic system.