Activation of group III metabotropic glutamate receptors in selected regions of the basal ganglia alleviates akinesia in the reserpine-treated rat

1 This study examined whether group III metabotropic glutamate (mGlu) receptor agonists injected into the globus pallidus (GP), substantia nigra pars reticulata (SNr) or intracerebroventricularly (i.c.v.) could reverse reserpine-induced akinesia in the rat. 2 Male Sprague-Dawley rats, cannulated above the GP, SNr or third ventricle, were rendered akinetic with reserpine (5 mg kg(-1) s.c.). 18 h later, behavioural effects of the group III mGlu receptor agonists L-serine-O-phosphate (L-SOP) or L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) were examined. 3 In reserpine-treated rats, unilateral injection of L-SOP (2000 and 2500 nmol in 2.5 mul) into the GP produced a significant increase in net contraversive rotations compared to vehicle, reaching a maximum of 83 +/- 21 rotations 120 min(-1) (n = 8). Pretreatment with the group III mGlu receptor antagonist methyl-serine-O-phosphate (M-SOP; 250 nmol in 2.5 mul) inhibited the response to L-SOP (2000 nmol) by 77%. 4 Unilateral injection of L-SOP (250-1000 nmol in 2.5 mul) into the SNr of reserpine-treated rats produced a dose-dependent increase in net contraversive rotations, reaching a maximum of 47+/-6 rotations 30 min(-1) (n = 6). M-SOP (50 nmol in 2.5 mul) inhibited the response to L-SOP (500 nmol) by 78%. 5 Following i.c.v. injection, L-SOP (2000-2500 nmol in 2.5 mul) or L-AP4 (0.5-100 nmol in 2 mul) produced a dose-dependent reversal of akinesia, attaining a maximum of 45 +/- 17 (n=8) and 72 +/- 3 (n = 9) arbitrary locomotor units 30 min(-1), respectively. 6 These studies indicate that injection of group III mGlu receptor agonists into the GP, SNr or cerebral ventricles reverses reserpine-induced akinesia, the mechanism for which remains to be established.