title: Dual modulation of gabaergic transmission by metabotropic glutamate receptors in rat ventral tegmental area.
abstract: 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.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: F
authors.initials: F
authors.lastname: Zheng
authors.forename: S W
authors.initials: SW
authors.lastname: Johnson
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D004594:Electrophysiology / Q000379:methods; D004745:Enkephalins / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009431:Neural Conduction / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000779:Anesthetics, Local; C419228:DCG 04; D004745:Enkephalins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; C474696:methyl-(4-carboxyphenyl)glycine; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D013779:Tetrodotoxin; D008734:Methoxyhydroxyphenylglycol; D005680:gamma-Aminobutyric Acid; D007930:Leucine; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine; D001640:Bicuculline