Activation of the mGlu7 receptor elicits antidepressant-like effects in mice.
BACKGROUND
Broad evidence indicates that modulation of the glutamatergic system could be an efficient way to achieve antidepressant activity. Metabotropic glutamate receptor (mGlu receptor) ligands seem to be promising agents to treat several central nervous system disorders, including psychiatric ones.


OBJECTIVE
The aim of our study was to investigate potential antidepressant-like activity of the first, selective, and bio-available mGlu7 receptor agonist, AMN082 (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride), in wild-type (WT) and mGlu7 receptor knock-out (KO) mice.


METHODS
The forced swim test (FST) and the tail suspension test (TST) in mice were used to assess antidepressant-like activity of AMN082.


RESULTS
We found that AMN082, administered IP, induced a dose-dependent decrease in the immobility time of WT animals in the FST and TST, suggesting antidepressant-like potency of an mGlu7 receptor agonist. Moreover, AMN082 did not change the behaviour of mGlu7 receptor KO mice compared to WT littermates in the TST, while imipramine, used as a reference control, significantly reduced their immobility, indicating an mGlu7 receptor-dependent mechanism of the antidepressant-like activity of AMN082. However, at high doses, AMN082 significantly decreased spontaneous locomotor activity of both mGlu7 receptor KO mice and WT control animals, suggesting off-target activity of AMN082 resulting in hypo-locomotion.


CONCLUSIONS
These results strongly suggest that activation of the mGlu7 receptor elicits antidepressant-like effects.
Palucha
Agnieszka
A
Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343, Krakow, Poland. nfpaluch@cyf-kr.edu.pl
Klak
Kinga
K
Branski
Piotr
P
van der Putten
Herman
H
Flor
Peter J
PJ
Pilc
Andrzej
A
D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D019417:Hindlimb Suspension / Q000379:methods; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D013550:Swimming; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D001559:Benzhydryl Compounds; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D007099:Imipramine