Decreased striatal dopamine in group II metabotropic glutamate receptor (mGlu2/mGlu3) double knockout mice

BMC Neuroscience

Paul J Harrison³  Trevor Sharp⁴  Elizabeth M Tunbridge³  James NC Kew¹  David M Bannerman²  Thomas Boerner²  Tracy A Lane³ 

[1] Neuroscience CEDD, GlaxoSmithKline, Harlow, UK;Department of Experimental Psychology, University of Oxford, Oxford, UK;Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK;Department of Pharmacology, University of Oxford, Oxford, UK

关键词: Nucleus accumbens;    Striatum;    HPLC;    Grm3;    Grm2;    mGlu3;    mGlu2;   

Others  :  1140083
DOI  :  10.1186/1471-2202-14-102

 received in 2013-04-30, accepted in 2013-09-17,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Lane et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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