A metabotropic glutamate 2/3 receptor antagonist, MGS0039, increases extracellular dopamine levels in the nucleus accumbens shell.
(1R,2R,3R,5R,6R)-2-Amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039), a potent and selective metabotropic glutamate 2/3 (mGlu 2/3) receptor antagonist, exhibits antidepressant-like activities in some animal models. In the present study, we examined the effect of MGS0039 on extracellular dopamine levels in the rat nucleus accumbens (NAc) shell using in vivo microdialysis evaluation because accumbal dopamine has been implicated in depression. Local application of MGS0039 into the NAc shell at 10 microM significantly increased extracellular dopamine levels in the NAc shell in freely moving rats. In contrast, local application of 10 microM of LY354740, an mGlu 2/3 receptor agonist, significantly decreased extracellular dopamine levels in the same brain region. These findings suggest that dopamine release in the NAc shell is regulated by mGlu 2/3 receptors, and that the effect on dopamine levels in the NAc shell may partially explain the antidepressant-like properties of mGlu 2/3 receptor antagonists.
Karasawa
Jun-ichi
J
Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama 331-9530, Japan.
Yoshimizu
Takao
T
Chaki
Shigeyuki
S
D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
C483757:2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo(3.1.0)hexane-2,6-dicarboxylic acid; D001643:Bridged Bicyclo Compounds; D003998:Dicarboxylic Acids; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C104753:eglumetad; D004298:Dopamine