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Keywords:

  • Akinesia;
  • group III metabotropic glutamate receptors;
  • globus pallidus;
  • in vivo;
  • substantia nigra pars reticulata;
  • rat;
  • reserpine;
  • Parkinson's disease
  • 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.

  • 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.

  • In reserpine-treated rats, unilateral injection of L-SOP (2000 and 2500 nmol in 2.5 μl) 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 μl) inhibited the response to L-SOP (2000 nmol) by 77%.

  • Unilateral injection of L-SOP (250-1000 nmol in 2.5 μl) 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 μl) inhibited the response to L-SOP (500 nmol) by 78%.

  • Following i.c.v. injection, L-SOP (2000–2500 nmol in 2.5 μl) or L-AP4 (0.5–100 nmol in 2 μl) 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.

  • 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.

British Journal of Pharmacology (2004) 141, 15–22. doi:10.1038/sj.bjp.0705566