Selective activation of metabotropic G-protein-coupled glutamate 7 receptor elicits anxiolytic-like effects in mice by modulating GABAergic neurotransmission.
We describe the anxiolytic-like effects of the first, selective metabotropic G-protein-coupled glutamate 7 (mGlu7) receptor agonist, N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), as measured in the modified stress-induced hyperthermia (SIH) and the four-plate tests. Administration of AMN082 (3-6 mg/kg intraperitoneally) to Swiss mice produced anxiolytic-like effects in the modified SIH and four-plate tests. Moreover, it was ineffective as an anxiolytic in the SIH test in mGlu7 receptor knockout mice as compared with wild-type C57BL/6J littermate controls. In contrast, diazepam (1.25-5 mg/kg) significantly reduced SIH in both the wild-type and knockout animals. The anxiolytic-like effect of AMN082 in the SIH paradigm was abolished by pretreatment with flumazenil (10 mg/kg intraperitoneally). This indicates an involvement of gamma-aminobutyric acid-ergic neurotransmission in AMN's anxiolytic actions. The results indicate that activation of the mGlu7 receptor produces anxiolytic-like effects via the modulation of the gamma-aminobutyric acid system.
Stachowicz
Katarzyna
K
Institute of Pharmacology, Polish Academy of Sciences, Smêtna, Kraków, Poland.
Brañski
Piotr
P
Kłak
Kinga
K
van der Putten
Herman
H
Cryan
John F
JF
Flor
Peter J
PJ
Andrzej
Pilc
P
D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000235:genetics*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001833:Body Temperature Regulation / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000235:genetics*; D013315:Stress, Psychological / Q000150:complications; D009435:Synaptic Transmission / Q000187:drug effects* / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001559:Benzhydryl Compounds; D018757:GABA Modulators; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid