RATIONALE: Metabotropic glutamate mGlu receptors 5 (mGluR5) receptors are abundant in corticolimbic circuitry where they modulate glutamate and dopamine signal transduction. OBJECTIVES: In this study, we explored the hypothesis that mGluR5 antagonist, (2-methyl-6-(phenylethynyl)pyridine hydrochloride) (MPEP), facilitates dopamine-dependent effects on memory and motor functions. METHODS: To this aim, we examined the effects of different doses (from 0 to 24 mg/kg) of the mGluR5 antagonist, MPEP, on the modulation of amphetamine-dependent behaviors, namely passive avoidance, locomotor activity, and rotation behavior in intact and dopamine-depleted CD1 male mice. RESULTS: We demonstrated that a low dose (3 mg/kg) of MPEP, which is void of behavioral effects on its own, facilitates amphetamine-induced effects independently on the behavior measured both in naïve and in dopamine-lesioned mice; this synergistic effect is lost when higher doses of MPEP are used. CONCLUSION: The results are discussed in terms of possible balance between dopamine and glutamate activity in regulating the proper fine tuning of information processing.
RATIONALE: Metabotropic glutamate mGlu receptors 5 (mGluR5) receptors are abundant in corticolimbic circuitry where they modulate glutamate and dopamine signal transduction. OBJECTIVES: In this study, we explored the hypothesis that mGluR5 antagonist, (2-methyl-6-(phenylethynyl)pyridine hydrochloride) (MPEP), facilitates dopamine-dependent effects on memory and motor functions. METHODS: To this aim, we examined the effects of different doses (from 0 to 24 mg/kg) of the mGluR5 antagonist, MPEP, on the modulation of amphetamine-dependent behaviors, namely passive avoidance, locomotor activity, and rotation behavior in intact and dopamine-depleted CD1 male mice. RESULTS: We demonstrated that a low dose (3 mg/kg) of MPEP, which is void of behavioral effects on its own, facilitates amphetamine-induced effects independently on the behavior measured both in naïve and in dopamine-lesioned mice; this synergistic effect is lost when higher doses of MPEP are used. CONCLUSION: The results are discussed in terms of possible balance between dopamine and glutamate activity in regulating the proper fine tuning of information processing.
Authors: F Gasparini; K Lingenhöhl; N Stoehr; P J Flor; M Heinrich; I Vranesic; M Biollaz; H Allgeier; R Heckendorn; S Urwyler; M A Varney; E C Johnson; S D Hess; S P Rao; A I Sacaan; E M Santori; G Veliçelebi; R Kuhn Journal: Neuropharmacology Date: 1999-10 Impact factor: 5.250
Authors: Jeffery J Anderson; Sara P Rao; Blake Rowe; Darlene R Giracello; Greg Holtz; Deborah F Chapman; Lida Tehrani; Margaret J Bradbury; Nicholas D P Cosford; Mark A Varney Journal: J Pharmacol Exp Ther Date: 2002-12 Impact factor: 4.030
Authors: Gert R J Christoffersen; Agnes Simonyi; Todd R Schachtman; Bettina Clausen; David Clement; Vicky K Bjerre; Louise T Mark; Mette Reinholdt; Kati Schmith-Rasmussen; Lena V B Zink Journal: Behav Brain Res Date: 2008-04-01 Impact factor: 3.332