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 microl) 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 microl) inhibited the response to L-SOP (2000 nmol) by 77%. Unilateral injection of L-SOP (250-1000 nmol in 2.5 microl) 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 microl) inhibited the response to L-SOP (500 nmol) by 78%. 4. Following i.c.v. injection, L-SOP (2000-2500 nmol in 2.5 microl) or L-AP4 (0.5-100 nmol in 2 microl) 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.
Neurodegenerative Disease Research Group, Wolfson Centre for Age-Related Diseases, Hodgkin Building, GKT School of Biomedical Sciences, King's College London, London SE1 1UL.
Nicholas
N
MacInnes
Marcus J
MJ
Messenger
Susan
S
Duty
D000613:Aminobutyrates / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism*; D018698:Glutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D018476:Hypokinesia / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009068:Movement / Q000187:drug effects / Q000502:physiology; D010768:Phosphoserine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000008:administration & dosage / Q000819:agonists* / Q000627:therapeutic use; D012110:Reserpine / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D000613:Aminobutyrates; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; D010768:Phosphoserine; D018698:Glutamic Acid; D012110:Reserpine; C012729:2-amino-4-phosphonobutyric acid