Jolanta Konieczny1, Tomasz Lenda. 1. Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. koniecz@if-pan.krakow.pl.
Abstract
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-diamine 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 reserpine-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 pmol/0.5 μl/ side vs. 25 and 75 pmol/0.5 μl/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.
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-diamine 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 reserpine-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 pmol/0.5 μl/ side vs. 25 and 75 pmol/0.5 μl/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.
Authors: Nidhi Jalan-Sakrikar; Julie R Field; Rebecca Klar; Margrith E Mattmann; Karen J Gregory; Rocio Zamorano; Darren W Engers; Sean R Bollinger; C David Weaver; Emily L Days; L Michelle Lewis; Thomas J Utley; Miguel Hurtado; Delphine Rigault; Francine Acher; Adam G Walker; Bruce J Melancon; Michael R Wood; Craig W Lindsley; P Jeffrey Conn; Zixiu Xiang; Corey R Hopkins; Colleen M Niswender Journal: ACS Chem Neurosci Date: 2014-10-09 Impact factor: 4.418