1 This study examined whether activation of group II metabotropic glutamate (mGlu) receptors in the substantia nigra pars reticulata (SNr) could reverse akinesia in a rodent model of Parkinson's disease (PD). 2 Male Sprague Dawley rats, stereotaxically cannulated above either the SNr or third ventricle, were rendered akinetic by injection of reserpine (5 mg kg 71 s.c.). Eighteen hours later, the rotational behaviour induced by unilateral injection of the group II mGlu receptor agonist, (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), was examined. 3 Following intranigral injection, DCG-IV (0.125 ± 0.75 nmol in 0.1 ml) produced a dose-dependent increase in net contraversive rotations (n=6 ± 8 animals per dose), reaching a maximum of 395+51 rotations 60 min 71 after 0.75 nmol. The eects of DCG-IV (0.5 nmol) were inhibited by 63.0+9.0% following 30 min pre-treatment with the group II mGlu receptor antagonist, (2S)-a-ethylglutamic acid (EGLU; 100 nmol in 0.2 ml; n=6). 4 Following intraventricular injection, DCG-IV (0.125 ± 1.5 nmol in 2 ml) produced a dosedependent increase in bilateral locomotor activity (n=6 ± 7 animals per dose), reaching a maximum of 180+21 locomotor units 30 min 71 after 0.5 nmol. Pre-treatment with EGLU (200 nmol in 2 ml) inhibited the eects of DCG-IV (0.5 nmol) by 68.2+12.3% (n=5). 5 These data show that activation of group II mGlu receptors in the SNr provides relief of akinesia in the reserpinized rat model of PD. The reversal seen following intraventricular administration supports the likely therapeutic bene®t of systemically-active group II mGlu receptor agonists in PD.
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