AMPA receptor mediates mGlu 2/3 receptor antagonist-induced dopamine release in the rat nucleus accumbens shell.

The role of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor activation in the regulation of dopamine release by the metabotropic glutamate (mGlu) 2/3 receptors in the nucleus accumbens (NAc) shell was investigated using an in vivo microdialysis evaluation. The local application of 10 μM of LY341495, an mGlu 2/3 receptor antagonist, significantly increased extracellular dopamine levels in the NAc shell in freely moving rats. Pretreatment with an AMPA receptor antagonist, NBQX (0.3 mg/kg, i.p.) significantly attenuated the increase in dopamine release induced by LY341495 application to the basal level, while the systemic administration of NBQX alone had no effect on dopamine release in this region of the brain. Moreover, the local application of an AMPA receptor potentiator, CX546, at 100 or 300 μM also enhanced dopamine release in the NAc shell in a concentration-dependent manner. These findings suggest that the activation of the postsynaptic AMPA receptor plays a role in mediating the regulation of dopamine release by the mGlu 2/3 receptor in the NAc shell.