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.