Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - The effect of mGlu8 deficiency in animal models of psychiatric diseases
AU - Fendt, M.
AU - Bürki, H.
AU - Imobersteg, S.
AU - van der Putten, H.
AU - McAllister, K.
AU - Leslie, J. C.
AU - Shaw, D.
AU - Hölscher, Christian
PY - 2010/2
Y1 - 2010/2
N2 - The metabotropic glutamate receptor subtype 8 (mGlu(8)) is presynaptically located and regulates the release of the transmitter. Dysfunctions of this mechanism are involved in the pathophysiology of different psychiatric disorders. mGlu(8) deficient mice have been previously investigated in a range of studies, but the results are contradictory and there are still many open questions. Therefore, we tested mGlu(8)-deficient animals in different behavioral tasks that are commonly used in neuropsychiatric research. Our results show a robust contextual fear deficit in mGlu(8)-deficient mice. Furthermore, novel object recognition, chlordiazepoxide-facilitated extinction of operant conditioning and the acoustic startle response were attenuated by mGlu(8) deficiency. We found no changes in sensory processing, locomotor activity, prepulse inhibition, phencyclidine-induced changes in locomotion or prepulse inhibition, operant conditioning, conditioned fear to a discrete cue or in animal models of innate fear and post-traumatic stress disorder. We conclude that mGlu(8) might be a potential target for disorders with pathophysiological changes in brain areas where mGlu(8) modulates glutamate and gamma-amino butyric acid (GABA) transmission. Our data especially point to anxiety disorders involving exaggerated contextual fear, such as generalized anxiety disorders, and to conditions with disturbed declarative memory.
AB - The metabotropic glutamate receptor subtype 8 (mGlu(8)) is presynaptically located and regulates the release of the transmitter. Dysfunctions of this mechanism are involved in the pathophysiology of different psychiatric disorders. mGlu(8) deficient mice have been previously investigated in a range of studies, but the results are contradictory and there are still many open questions. Therefore, we tested mGlu(8)-deficient animals in different behavioral tasks that are commonly used in neuropsychiatric research. Our results show a robust contextual fear deficit in mGlu(8)-deficient mice. Furthermore, novel object recognition, chlordiazepoxide-facilitated extinction of operant conditioning and the acoustic startle response were attenuated by mGlu(8) deficiency. We found no changes in sensory processing, locomotor activity, prepulse inhibition, phencyclidine-induced changes in locomotion or prepulse inhibition, operant conditioning, conditioned fear to a discrete cue or in animal models of innate fear and post-traumatic stress disorder. We conclude that mGlu(8) might be a potential target for disorders with pathophysiological changes in brain areas where mGlu(8) modulates glutamate and gamma-amino butyric acid (GABA) transmission. Our data especially point to anxiety disorders involving exaggerated contextual fear, such as generalized anxiety disorders, and to conditions with disturbed declarative memory.
KW - Animals
KW - Anxiety Disorders
KW - Chlordiazepoxide
KW - Conditioning (Psychology)
KW - Conditioning, Operant
KW - Disease Models, Animal
KW - Extinction, Psychological
KW - Fear
KW - Hyperkinesis
KW - Maze Learning
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Motor Activity
KW - Pattern Recognition, Visual
KW - Phencyclidine
KW - Receptors, Metabotropic Glutamate
KW - Startle Reaction
U2 - 10.1111/j.1601-183X.2009.00532.x
DO - 10.1111/j.1601-183X.2009.00532.x
M3 - Journal article
C2 - 19740090
VL - 9
SP - 33
EP - 44
JO - Genes, Brain and Behavior
JF - Genes, Brain and Behavior
SN - 1601-183X
IS - 1
ER -