The effects of local perfusion of DAMGO on extracellular GABA and glutamate concentrations in the rostral ventromedial medulla |
| |
Authors: | Schepers Raf Jan-Filip Mahoney Janet Lynn Zapata Agustin Chefer Vladimir Shippenberg Toni Shaun |
| |
Affiliation: | University of Maryland School of Medicine, Baltimore, Maryland, USA; Integrative Neuroscience Section, Behavioral Neurosciences Branch, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA |
| |
Abstract: | Electrophysiological data suggest an involvement of rostral ventromedial medulla (RVM) GABA and glutamate (GLU) neurons in morphine analgesia. Direct evidence that extracellular concentrations of GABA or GLU are altered in response to mu opioid receptor (MOP-R) activation is, however, lacking. We used in vivo microdialysis to investigate this issue. Basal GABA overflow increased in response to intra-RVM perfusion of KCl (60 mmol/L). Reverse microdialysis of the MOP-R agonist d -Ala(2),NMePhe(4),Gly-ol(5)]enkephalin (DAMGO) (20–500 μmol/L) produced a concentration-dependent decrease of RVM GABA overflow. Behavioral testing revealed that concentrations that decreased GABA levels increased thermal withdrawal thresholds. A lower agonist concentration that did not increase GABA failed to alter thermal thresholds. DAMGO did not alter GLU concentrations. However, KCl also failed to modify GLU release. Since rapid, transporter-mediated uptake may mask the detection of changes in GLU release, the selective excitatory amino acid transporter inhibitor pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mmol/L) was added to the perfusion medium for subsequent studies. tPDC increased GLU concentrations, confirming transport inhibition. KCl increased GLU dialysate levels in the presence of tPDC, demonstrating that transport inhibition permits detection of depolarization-evoked GLU overflow. In the presence of tPDC, DAMGO increased GLU overflow in a concentration-dependent manner. These data demonstrate that MOP-R activation decreases GABA and increases GLU release in the RVM. We hypothesize that the opposing effects of MOP-R on GLU and GABA transmission contribute to opiate antinociception. |
| |
Keywords: | analgesia GABA glutamate microdialysis rostral ventromedial medulla |
本文献已被 PubMed 等数据库收录! |
|