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

Abstract

BackgroundMetabotropic 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-diamine dihydrochloride (AMN082) is a potent, brain penetrating mGluR7 agonist, selective over other mGluRs. MethodsThe 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 reserpine-induced akinesia models in rats; (2) striatal and nigral mGluR7 is likely to contribute to such an effect. ResultsWe found that AMN082 (1 and 3mg/kg) decreased the haloperidol (0.25mg/kg)-induced catalepsy, but was not efficient in attenuating the reserpine (2.5mg/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 7.5pmol/0.5μl/ side vs. 25 and 75pmol/0.5μl/side, respectively). ConclusionThe 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.