Group III metabotropic glutamate receptors act as hetero-receptors modulating evoked GABA release in the globus pallidus in vivo

Blunted mGluR Activation Disinhibits Striatopallidal Transmission in Parkinsonian Mice

“…As group II mGluRs at the striatopallidal synapse are tonically active, local glutamate levels at the striatopallidal synapses can be in the submicromolar range based on the affinity of these receptors to glutamate (Schoepp et al, 1999). In contrast, group III mGluRs that are present at striatopallidal synapses and exhibit micromolar affinity for glutamate are not tonically active (Macinnes and Duty, 2008; Matsui and Kita, 2003; Valenti et al, 2003). …”

Rapid analysis of GABA and glutamate in microdialysis samples using high performance liquid chromatography and tandem mass spectrometry

“…To date, the most common method for the detection of GABA and glutamate in microdialysates is HPLC-FD (Kehr, 1998a;Kehr, 1998b;Bianchi et al, 1999;Rea et al, 2005;Ballini et al, 2008) or more rarely HPLC-ECD (Kehr, 1998b;Macinnes and Duty, 2008). Amino acids are polar molecules which offer low affinity for reversed phase columns.…”

“…In vivo microdialysis is a widely used technique to continuously monitor alterations of neurotransmitters in the extracellular fluid of the brain. The analytical standard technique to measure GABA and glutamate in microdialysates is high performance liquid chromatography (HPLC) coupled with fluorescence detection (HPLC-FD) (Kehr, 1998a;Kehr, 1998b;Bianchi et al, 1999;Rea et al, 2005;Ballini et al, 2008) or electrochemical detection (HPLC-ECD) (Kehr, 1998b;Macinnes and Duty, 2008). Especially for the analysis of GABA in microdialysis samples, HPLC conditions are critical (Rea et al, 2005).…”

Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indications

“…The mGlu 4 receptor is highly expressed presynaptically at the first synapse in the indirect pathway (the striatopallidal synapse) (Bradley, Standaert et al 1999), thus providing an exciting alternative approach to rebalance the basal ganglia circuitry for PD treatment. Administration of the group III mGlu agonists L-AP4 or L-SOP, and recently the more mGlu 4 -selective agonists LSP1-2111 and LSP4-2022, has been shown to reduce GABAergic transmission at the striatopallidal synapse and demonstrate efficacy in several rodent PD models, including haloperidol-induced catalepsy and 6-OHDA-induced motor deficits (Wittmann, Marino et al 2001, Matsui and Kita 2003, Valenti, Marino et al 2003, MacInnes, Messenger et al 2004, Macinnes and Duty 2008, Beurrier, Lopez et al 2009, Goudet, Vilar et al 2012). Recently, numerous highly selective mGlu 4 PAMs have been developed from different chemical series and exhibit robust efficacy in preclinical rodent models.…”