The mGlu2/3 receptor agonist, LY354740, blocks immobilization-induced increases in noradrenaline and dopamine release in the rat medial prefrontal cortex.
The metabotropic glutamate (mGlu2/3) receptor agonist, LY354740, exhibits anxiolytic-like properties in a number of rodent models. The present study utilized in vivo microdialysis to examine the effects of LY354740 on extracellular monoamine levels in the medial prefrontal cortex (mPFC) of animals subjected to 30 min immobilization stress. Immobilization stress significantly elevated extracellular levels of noradrenaline (NA) and dopamine (DA) in the mPFC, while systemic administration of LY354740 (30 mg/kg, s.c.) significantly attenuated immobilization-induced increases in both NA and DA. Reverse-dialysis of LY354740 (30 microm) into the mPFC significantly attenuated immobilization-induced increases in NA, but not DA without affecting basal levels of either amine. In separate studies in the presence of citalopram (1 microm; reverse dialysis into the mPFC), systemic administration of LY354740 attenuated immobilization-induced increases in NA and DA, but had no effect on serotonin (5-HT) levels. Co-administration of the selective mGlu2/3 receptor antagonist, LY341495, partially or fully reversed the attenuation in NA and DA levels produced by LY354740, respectively. Taken together, these data suggest that LY354740 may produce anti-stress actions, in part, by blocking stress-related increases in catecholamines in the mPFC via mGlu2/3 receptor stimulation.
Swanson
Chad J
CJ
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Perry
Kenneth W
KW
Schoepp
Darryle D
DD
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism; D012149:Restraint, Physical; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D002395:Catecholamines; D015283:Citalopram; D004298:Dopamine; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009638:Norepinephrine; D018094:Receptors, Metabotropic Glutamate; D017367:Selective Serotonin Reuptake Inhibitors; D014966:Xanthenes; C114624:LY 341495; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104753:eglumetad