dcg-04 and 3-4-dihydroxyphenylglycol

The effects of metabotropic glutamate receptor (mGluR) activation on non-dopamine (putative GABAergic) neurons and inhibitory synaptic transmission in the ventral tegmental area were examined using intracellular recordings from rat midbrain slices. Perfusion of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD; agonist for group I and II mGluRs), but not L-amino-4-phosphonobutyric acid (L-AP4; agonist for group III mGluRs), produced membrane depolarization (current clamp) and inward current (voltage clamp) in non-dopamine neurons. The t-ACPD-induced depolarization was concentration-dependent (concentration producing 50% maximal depolarization [EC(50)]=6.1+/-2.5 microM), and was blocked by the antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine, but not by tetrodotoxin and ionotropic glutamate-receptor antagonists. The t-ACPD-evoked responses were mimicked comparably by selective group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG). Furthermore, the DHPG-induced depolarization in non-dopamine neurons was greatly reduced by mGluR1-specific antagonist 7(hydroxyimino)cyclopropachromen-1a-carboxylate ethyl ester. When recorded in dopamine neurons, the frequency of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic potentials was increased by t-ACPD but not L-AP4. However, the amplitude of evoked inhibitory postsynaptic currents in dopamine neurons was reduced by all three group mGluR agonists. These results reveal a dual modulation of mGLuR activation on inhibitory transmission in midbrain ventral tegmental area: enhancing putative GABAergic neuronal excitability and thus potentiating tonic inhibitory synaptic transmission while reducing evoked synaptic transmission at inhibitory terminals.

Topics: Anesthetics, Local; Animals; Bicuculline; Cycloleucine; Dopamine; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Electrophysiology; Enkephalins; Excitatory Amino Acid Antagonists; GABA Antagonists; gamma-Aminobutyric Acid; Glycine; In Vitro Techniques; Leucine; Male; Membrane Potentials; Methoxyhydroxyphenylglycol; Neural Conduction; Neural Inhibition; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate; Synaptic Transmission; Tetrodotoxin; Ventral Tegmental Area