Intrastriatal AP5 differentially affects behaviors induced by local infusions of D1 vs. D2 dopamine agonists

Using bilateral infusions into the rat striatum, the effects of the competitive NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (AP5) on behaviors induced by the dopamine (DA) D1 receptor agonist SKF 82526 (fenoldopam) or the D2 receptor agonist quinpirole were determined. These effects were tested in DA-replete (intact) rats and in rats that were receiving injections of the monoamine-depleting drug reserpine. In both intact and reserpinized rats, fenoldopam induced significant sniffing. This effect was attenuated by simultaneous co-infusion of AP5 in the reserpinized rats. Quinpirole induced locomotion, sniffing, and oral behaviors, all of which were attenuated by AP5 co-infusion in the intact rats. In contrast, AP5 enhanced the quinpirole-induced sniffing of reserpinized rats. These findings suggest that distinct D1/glutamate and D2/glutamate relationships exist in the striatum, and that the nature of the latter is influenced by DA tone.