Contribution of the mGluR7 receptor to antiparkinsonian-like effects in rats: a behavioral study with the selective agonist AMN082

Background: Metabotropic glutamate receptors (mGluRs) have been shown to be potential targets for numerous neurological diseases, including Parkinson's disease (PD). We previously reported that ACPT-1, a non-selective group III mGluRs agonist, injected locally into the globus pallidus, striatum or substantia nigra pars reticulata (SNr), significantly attenuated the haloperidol-induced catalepsy in rats. N,N'-dibenzhydryl-ethane-1,2-diarnine dihydrochloride (AMN082) is a potent, brain penetrating mGluR7 agonist, selective over other mGluRs. Methods: The aim of the present study was to determine whether (1) activation of mGluR7 by systemic administration of AMN082 may produce antiparkinsonian-like effects in the haloperidol-induced catalepsy and resetpine-induced akinesia models in rats; (2) striatal and nigral mGluR7 is likely to contribute to such an effect. Results: We found that AMN082 (1 and 3 mg/kg) decreased the haloperidol (0.25 mg/kg)-induced catalepsy, but was not efficient in attenuating the reserpine (2.5 mg/kg)-induced akinesia. When given locally, AMN082 also significantly diminished catalepsy in rats; however, its effective striatal doses were 10-fold lower than those used in the SNr (2.5 and 7.5 pmo1/0.5 mu l/ side vs. 25 and 75 pmo1/0.5 mu l/side, respectively). Conclusion: The above findings support the idea that the activation of mGluR7 can produce antiparkinsonian-like effects in rats. Furthermore, our results indicate contribution of both striatal and nigral mGluR7 to the anticataleptic effects of AMN082.