The mGlu2/3 receptor agonist LY354740 suppresses immobilization stress-induced increase in rat prefrontal cortical BDNF mRNA expression.
Both a 5-hydroxytryptamine2A (5-HT2A) agonist and immobilization stress previously have been shown to differentially alter brain-derived neurotrophic factor (BDNF) mRNA expression in the neocortex and hippocampus. Both 5-HT2A receptor activation and immobilization stress also increase glutamate release in the rat prefrontal cortex. Given that the metabotropic glutamate2/3 receptor (mGluR2/3) agonist (1S,2S,5R,6S)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylate monohydrate (LY354740) suppressed electrophysiological, behavioral and biochemical effects of 5-HT2A receptor activation in the medial prefrontal cortex (mPFC), we assessed the efficacy of the mGluR2/3 agonist in suppressing the stress-induced increase in BDNF mRNA expression. LY35740 (10 mg/kg, i.p.) attenuated the immobilization stress-induced increase in BDNF mRNA expression in the rat mPFC. This result is consistent with the hypothesis that mGlu2/3 agonists may be an efficacious treatment for stress-induced neuropsychiatric syndromes.
Yale School of Medicine, Department of Psychiatry, Ribicoff Research Facilities of the Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA.
Younglim
Y
Lee
Ronald S
RS
Duman
Gerard J
GJ
Marek
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D007103:Immobilization; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013315:Stress, Psychological / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D001643:Bridged Bicyclo Compounds; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104753:eglumetad