Striatal NTS₁, dopamine D₂ and NMDA receptor regulation of pallidal GABA and glutamate release – a dual‐probe microdialysis study in the intranigral 6‐hydroxydopamine unilaterally lesioned rat

Abstract

The current microdialysis study elucidates a functional interaction between the striatal neurotensin NTS(1) receptor and the striatal dopamine D(2) and N-methyl-d-aspartic acid (NMDA) receptors in the regulation of striatopallidal gamma-aminobutyric acid (GABA) and glutamate levels after an ipsilateral intranigral 6-hydroxydopamine-induced lesion of the ascending dopamine pathways to the striatum. Lateral globus pallidus GABA levels were higher in the lesioned group while no change was observed in striatal GABA and glutamate levels. The 6-hydroxydopamine-induced lesion did not alter the ability of intrastriatal NT (10 nm) to counteract the decrease in pallidal GABA and glutamate levels induced by the dopamine D(2) -like receptor agonist quinpirole (10 μm). A more pronounced increase in the intrastriatal NMDA- (10 μm) induced increase in pallidal GABA levels was observed in the lesioned group while it attenuated the increase in striatal glutamate levels and amplified the increase in pallidal glutamate levels compared with that observed in the controls. NT enhanced the NMDA-induced increase in pallidal GABA and glutamate and striatal glutamate levels; these effects were counteracted by the NTS(1) antagonist SR48692 (100 nm) in both groups. These findings demonstrate an inhibitory striatal dopamine D(2) and an excitatory striatal NMDA receptor regulation of striatopallidal GABA transmission in both groups. These actions are modulated by NT via antagonistic NTS(1) /D(2) and facilitatory NTS(1) /NMDA receptor-receptor interactions, leading to enhanced glutamate drive of the striatopallidal GABA neurons associated with motor inhibition, effects which all are counteracted by SR48692. Thus, NTS(1) antagonists in combination with conventional treatments may provide a novel therapeutic strategy in Parkinson's disease.

Acute cocaine treatment enhances the antagonistic allosteric adenosine A2A-dopamine D2 receptor–receptor interactions in rat dorsal striatum without increasing significantly extracellular dopamine levels

“…The surgery with the microdialysis probe implantation into the right or left striatum and microdialysis experiments were performed based on the methods described previously [35,36]. A microdialysis probe of concentric design (molecular weight cut-off, 20 kDa; CMA 12; outer diameter, 0.5 mm; length of dialysing membrane, 2 mm; Carnegie Medicine, Stockholm, Sweden) was used.…”

Diverse Roles of Neurotensin Agonists in the Central Nervous System

“…NT increases glutamate release in the striatum, globus pallidus, frontal cortex, and SN (Ferraro et al, 2011, 2012) implicating NT in conditions such as stroke, Alzheimer’s disease, and PD.…”

Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders

“…However, the mechanism behind this effect is unclear since other studies have suggested that NT alone promotes glutamatergic signaling (Ferraro et al, 2011). NTS1 has been shown to functionally interact with glutamatergic NMDA receptors, potentiating NMDA receptor function (Ferraro et al, 2012). Alcohol is a known to inhibit NMDA function (Lovinger et al, 1989).…”