Antidepressant and anxiolytic-like effects in mice lacking the group III metabotropic glutamate receptor mGluR7.
Glutamatergic neurotransmission has been strongly implicated in the pathophysiology of affective disorders, such as major depression and anxiety. Of all glutamate receptors, the role of group III metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7, mGluR8) in such disorders is the least investigated because of the lack of specific pharmacological tools. To this end, we examined the behavioural profiles of mice with a targeted deletion of the gene for mGluR7 (mGluR7-/-) in animal models of depression and anxiety. mGluR7-/- mice were compared with wild-type (mGluR7+/+) littermates and showed substantially less behavioural immobility in both the forced swim test and the tail suspension test. Both behavioural paradigms are widely used to predict antidepressant-like activity. Further, mGluR7-/- mice displayed anxiolytic activity in four different behavioural tests, i.e. the light-dark box, the elevated plus maze, the staircase test, and the stress-induced hyperthermia test, while their cognitive performance was normal in the passive avoidance paradigm. Analysis of locomotor activity in a novel environment demonstrated that mGluR7-/- mice were slightly more active in the initial minutes following placement in the chamber only. Together, these data suggest that mGluR7 may play a pivotal role in mechanisms that regulate behavioural responses to aversive states. Therefore, drugs acting at mGluR7 may provide novel treatments for psychiatric disorders such as depression and anxiety.
Cryan
John F
JF
Nervous System Research, Novartis Institutes for BioMedical Sciences, Novartis Pharma AG, Basel, Switzerland. john_f.cryan@pharma.novartis.com
Kelly
Peter H
PH
Neijt
Hans C
HC
Sansig
Gilles
G
Flor
Peter J
PJ
van Der Putten
Herman
H
D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology; D001362:Avoidance Learning / Q000502:physiology; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D005239:Fear; D005260:Female; D019417:Hindlimb Suspension / Q000502:physiology; D007103:Immobilization; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000502:physiology; D011597:Psychomotor Performance; D011930:Reaction Time / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013312:Stress, Physiological
D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7