Increased glutamate release in the substantia nigra pars reticulata (SNr), from overactive subthalamic nucleus efferents, contributes to the akinesia seen in Parkinson’s disease. Our previous studies indicate that activation of two types of group III metabotropic glutamate (mGlu) receptor, mGlu4 and mGlu7, can inhibit glutamate release in slices of rat SN (Austin et al. 2006). The aim of the present study was to establish whether modulation of these same receptors in vivo, using N-phenyl-7-(hydroxyamino) cyclopropa[b]chromen-1a-carboxamide (PHCCC), the positive allosteric modulator of mGlu4, and N’-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), the selective mGlu7 allosteric agonist, could reverse akinesia in the reserpine-treated rat. Male Sprague-Dawley rats were stereotaxically cannulated (under isoflurane inhalation: 4% in 95% O₂-5% CO₂; maintained during surgery with 2% isoflurane in the same O₂-CO₂ mix)) 2 mm above the SNr. 7 days post-surgery they were rendered akinetic using reserpine (4mg kg^-1 s.c.). Once akinetic (~18 h later), rats received a single unilateral intranigral injection (2.5 μl) of either PHCCC (3-75 nmol), AMN082 (3-100 nmol) or vehicle (40% DMSO in PBS). In some cases, the ability of the group III mGlu receptor antagonist, (RS)-cyclopropyl-4-phosphonophenylglycine (CPPG), to reverse these effects was tested by intranigral injection of 75 nmol CPPG 30 min prior to injection of PHCCC (75 nmol) or AMN082 (100nmol). Locomotor activity was recorded for 60 min post-injection and the number of 360^o contraversive rotations quantified as a measure of relief of akinesia. Treatment groups were compared using either a 1-way ANOVA with student Newman-Keuls post hoc test or, for the antagonist study alone, an unpaired t-test (5% level). PHCCC (3-75nmol) produced a dose-dependent reversal of akinesia reaching 141±28 rotations 60 min^-1 (75 nmol PHCCC) compared with vehicle (11±8 rotations 60 min^-1 ;P<0.01). AMN082 (3-100 nmol) also produced a dose-dependent reversal of akinesia reaching 226±75 rotations 60 min^-1 (100 nmol AMN082) compared with vehicle (17±9 rotations 60 min^-1; P<0.05). For both PHCCC (75nmol) and AMN082 (100nmol), pre-treatment with the group III antagonist, CPPG (75nmol), inhibited the response by 71% and 70%, respectively. Both PHCCC and AMN082 were able to reverse reserpine-induced akinesia, an effect blocked by the group III mGlu antagonist, CPPG. These data support a role for both mGlu4 and mGlu7 receptor sub-types in mediating this response. On the basis of our previous in vitro data (Austin et al. 2006), these anti-akinetic effects most likely reflect inhibition of abnormally-elevated glutamate release within the SNr of the reserpine-treated rat.