Regional localization of dopamine and ionotropic glutamate receptor subtypes in striatolimbic brain regions

Localization of dopamine (D(1)-, D(2)-like, and D(4)) and ionotropic glutamate (NMDA, AMPA, and KA) receptor subtypes within the striatolimbic forebrain remains incomplete, but basic to understanding the functional organization of this important brain region. We found that frontal cortical ablation supported colocalization of D(4) and NMDA receptors on corticostriatal afferents to caudate-putamen and nucleus accumbens in rat forebrain. Local injection of kainic acid into caudate-putamen, nucleus accumbens, or hippocampus produced massive local postsynaptic losses of D(1)- and D(2)-like, as well as NMDA, AMPA, and KA receptors, and kainic acid ablation of hippocampal-striatal projections indicated the selective expression of presynaptic NMDA and KA autoreceptors. Degeneration of nigrostriatal dopamine projections with 6-hydroxydopamine showed that all three glutamatergic subtypes exist as heteroceptors on nigrostriatal dopaminergic terminals. Our findings suggest common interactions between excitatory glutamatergic and inhibitory dopaminergic receptors in rat forebrain. Further localization of these receptor subtypes in striatolimbic forebrain should help to clarify their contributions to the pathophysiology of neuropsychiatric disorders and their treatment.