Metabotropic glutamate receptors depress glutamate-mediated synaptic input to rat midbrain dopamine neurones in vitro
Version of Record online: 3 FEB 2009
1998 British Pharmacological Society
British Journal of Pharmacology
Volume 123, Issue 4, pages 667–674, February 1998
How to Cite
Wigmore, M. A. and Lacey, M. G. (1998), Metabotropic glutamate receptors depress glutamate-mediated synaptic input to rat midbrain dopamine neurones in vitro. British Journal of Pharmacology, 123: 667–674. doi: 10.1038/sj.bjp.0701662
- Issue online: 3 FEB 2009
- Version of Record online: 3 FEB 2009
- (Received August 22, 1997, Revised October 21, 1997, Accepted November 10, 1997)
- Dopamine neurones;
- basal ganglia;
- metabotropic glutamate receptors;
- glutamate receptor agonists;
- glutamate receptor antagonists;
- phenylglycine derivatives;
- synaptic potentials;
- intracellular recording;
- brain slices
Glutamate (AMPA receptor-mediated) excitatory postsynaptic potentials (e.p.s.ps.), evoked by electrical stimulation rostral to the recording site, were examined by intracellular microelectrode recording from dopamine neurones in parasagittal slices of rat ventral midbrain.
The e.p.s.p. was depressed by the group III metabotropic glutamate (mGlu) receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP4; 0.01–30 μM) by up to 60% with an EC50 of 0.82 μM. The depression induced by L-AP4 (3 μM) was reversed by the group III preferring mGlu receptor antagonist, α-methyl-4-phosphonophenylglycine (MPPG; 250 μM).
The group I and II mGlu agonist, 1S,3R-aminocyclopentanedicarboxylic acid (ACPD; 3–30 μM) also depressed the e.p.s.p. in a concentration-dependent manner. The effect of ACPD (10 μM) was reversed by (+)-α-methyl-4-carboxyphenylglycine (MCPG; 1 mM; 4 cells). This effect of ACPD was also partially antagonized (by 50.3±15.7%, 4 cells) by MPPG (250 μM).
The selective agonist at group I mGlu receptors, dihydroxyphenylglycine (DHPG; 100 μM), decreased e.p.s.p. amplitude by 27.1±8.2% (7 cells), as did the group II mGlu receptor-selective agonist (1S,1′R,2′R,3′R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 1 μM) by 26.7±4.3% (5 cells).
DHPG (10–100 μM) caused a depolarization of the recorded cell, as did ACPD (3–30 μM), whereas no such postsynaptic effect of either L-AP4 or DCG-IV was observed.
These results provide evidence for the presence of presynaptic inhibitory metabotropic glutamate autoreceptors from the mGlu receptor groups II and III on descending glutamatergic inputs to midbrain dopamine neurones. Group I mGlu receptors mediate a postsynaptic depolarization, and can also depress glutamatergic transmission, but may not necessarily be localized presynaptically. These sites represent novel drug targets for treatment of schizophrenia and movement disorders of basal ganglia origin.
British Journal of Pharmacology (1998) 123, 667–674; doi:10.1038/sj.bjp.0701662