Related functions of mGlu4 and mGlu8.
Metabotropic glutamate receptors modulate glutamatergic and GABAergic neurotransmission. Our previous pharmacological data indicate that metabotropic receptor 4 (mGlu4) and metabotropic receptor 8 (mGlu8) might have related and overlapping functions. We explored this by analyzing the behavioral phenotypes of mice deficient in either (mGlu4(-/-) or mGlu8(-/-)) or both receptors (mGlu4/8(-/-)). Our analysis focused on measures of anxiety in the open field and elevated zero maze, sensorimotor function on the rotarod and fear conditioning, as mGlu4 and/or mGlu8 were shown to affect performance in these tests. mGlu8(-/-) mice weighed more than mGlu4/8(-/-) mice. In the open field, mGlu4(-/-) mice showed lower levels of anxiety than mGlu8(-/-) and mGlu4/8(-/-) mice. In the elevated zero maze, mGlu4(-/-) mice showed lower levels of anxiety than wild-type, mGlu8(-/-) and mGlu4/8(-/-) mice. In the open field, but not elevated zero maze, mGlu4(-/-) mice showed lower activity levels than wild-type, mGlu8(-/-) and mGlu4/8(-/-) mice. mGlu4/8(-/-) female mice showed less contextual freezing than wild-type and mGlu4(-/-) female mice and there was a trend toward less freezing in male mGlu4/8(-/-) than wild-type male mice. There were no genotype differences in cued fear conditioning. There were significant negative correlations between body weight and fall latency on the rotarod in wild-type, mGlu8(-/-) and mGlu4/8(-/-), but not mGlu4(-/-), mice. These data suggest related functions of mGlu4 and mGlu8 in behavioral performance.
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Matthew J
MJ
Davis
Robert M
RM
Duvoisin
Jacob
J
Raber
D000818:Animals; D001522:Behavior, Animal; D005239:Fear; D005260:Female; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*
D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8; C108823:metabotropic glutamate receptor 4
Body weight; Fear conditioning; Open field; Zero maze; mGlu4; mGlu8