Dopamine-glutamate reciprocal modulations play a major integrative role in the striatum. Glutamate acts on two types of glutamatergic receptors, ionotropic glutamatergic receptors (NMDA, AMPA and kainate) and metabotropic glutamatergic receptors that are G-protein coupled. Ionotropic NMDA receptors are found postsynaptically on GABA neurons [19]. These receptors are also expressed presynaptically on dopaminergic terminals [20]. NMDA receptor activation has been shown to enhance stimulated dopamine release in slice preparations. This facilitating action was reversed by NMDA receptor antagonists and was resistant to TTX, indicating that the receptors being activated are presynaptically located [21, 22].
In contrast, previous voltammetric studies have shown that the activation of NMDA receptors inhibits dopamine release [23, 24].
Thus it seems that NMDA receptor activation can have both a facilitatory and inhibitory effect on dopaminergic transmission. Conversely dopamine has also been shown to modulate glutamate release. Dopamine D2-like receptors are involved in the presynaptic inhibition of glutamatergic transmission [25]. The general consensus is that the receptors involved in the control of glutamate release throughout the striatum belong to the D2-like [26], but not the D1-like receptor family. The presence and the function of D1-like receptors on corticostriatal terminals is still a matter of some debate.
A1 receptors located on corticostriatal terminals inhibit transmitter release through the blockade of Ca2+ AV-951 currents [27].
As A1 receptors are located on glutamatergic terminals, it has been suggested that the ability of A1 receptors to modulate dopamine release is secondary to their ability Entinostat to decrease glutamate release, resulting in a decrease in the activation of ionotropic glutamate receptors localized in dopaminergic terminals [12]. In the first section of the present study we investigate the role that NMDA receptor activation plays in the modulation of dopamine release and the influence of adenosine A1 receptors in this modulation.GABA plays a central role in the processing of information in the striatum. There are two neuronal sources of GABA in the striatum, spiny projection neurons and intrinsic GABAergic interneurons.
The spiny projection neurons are the prinicipal efferent cells of the striatum. These neurons receive excitatory input from motor cortices and thalamus and dopamine input from midbrain dopamine cells. Dopaminergic input is critical for the control of movement by the basal ganglia; its loss leads to the Site URL List 1|]# motor deficits observed in Parkinson’s disease.