BACKGROUND: Group II metabotropic glutamate receptors (mGlu2 and mGlu3, encoded by Grm2 and Grm3) have been the focus of attention as treatment targets for a number of psychiatric conditions. Double knockout mice lacking mGlu2 and mGlu3 (mGlu2/3-/-) show a subtle behavioural phenotype, being hypoactive under basal conditions and in response to amphetamine, and with a spatial memory deficit that depends on the arousal properties of the task. The neurochemical correlates of this profile are unknown. Here, we measured tissue levels of dopamine, 5-HT, noradrenaline and their metabolites in the striatum and frontal cortex of mGlu2/3-/- double knockout mice, using high performance liquid chromatography. We also measured the same parameters in mGlu2-/- and mGlu3-/- single knockout mice. RESULTS: mGlu2/3-/-mice had reduced dopamine levels in the striatum but not in frontal cortex, compared to wild-types. In a separate cohort we replicated this deficit and, using tissue punches, found it was more prominent in the nucleus accumbens than in dorsolateral striatum. Noradrenaline, 5-HT and their metabolites were not altered in the striatum of mGlu2/3-/- mice, although the noradrenaline metabolite MHPG was increased in the cortex. In mGlu2-/- and mGlu3-/- single knockout mice we found no difference in any monoamine or metabolite, in either brain region, compared to their wild-type littermates. CONCLUSIONS: Group II metabotropic glutamate receptors impact upon striatal dopamine. The effect may contribute to the behavioural phenotype of mGlu2/3-/- mice. The lack of dopaminergic alterations in mGlu2-/- and mGlu3-/- single knockout mice reveals a degree of redundancy between the two receptors. The findings support the possibility that interactions between mGlu2/3 and dopamine may be relevant to the pathophysiology and therapy of schizophrenia and other disorders.
Animals, Brain Chemistry, Chromatography, High Pressure Liquid, Corpus Striatum, Dopamine, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Metabotropic Glutamate