PMID: 10711353: Akinesia alleviated by glutamate receptor agonist DCG-IV in the rat

[janet paterson <janet313@xxxxxxxxxxx>]

The group II metabotropic glutamate receptor agonist, DCG-IV, alleviates
akinesia following intranigral or intraventricular administration in the
reserpine-treated rat.

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-1 
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 microliter) 
produced a dose-dependent increase in net contraversive rotations (n = 6-8 
animals per dose), reaching a maximum of 395 +/- 51 rotations 60 min-1 after 
0.75 nmol.

The effects 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)-alpha-ethylglutamic acid (EGLU; 100 nmol in 0.2 microliter; n = 6).

4. Following intraventricular injection, DCG-IV (0.125-1.5 nmol in 2 
microliters) produced a dose-dependent increase in bilateral locomotor activity 
(n = 6-7 animals per dose), reaching a maximum of 180 +/- 21 locomotor units 30 
min-1 after 0.5 nmol.

Pre-treatment with EGLU (200 nmol in 2 microliters) inhibited the effects 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 benefit of systemically-active group II mGlu receptor agonists in 
PD.


Br J Pharmacol 2000 Feb;129(3):541-6
Dawson L, Chadha A, Megalou M, Duty S
Neurodegenerative Disease Research Group, Wolfson Centre for Age-Related
Diseases, GKT School of Biomedical Sciences, King's College London.

PMID: 10711353, UI: 20176693



janet paterson
53 now / 41 dx / 37 onset
a new voice: 
613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0