title: Cocaine Decreases Metabotropic Glutamate Receptor mGluR1 Currents in Dopamine Neurons by Activating mGluR5.
abstract: Midbrain dopamine neurons are important mediators of reward and movement and are sensitive to cocaine-induced plasticity. After even a single injection of cocaine, there is an increase in AMPA-dependent synaptic transmission. The present study examines cocaine-induced plasticity of mGluR-dependent currents in dopamine neurons in the substantia nigra. Activation of mGluR1 and mGluR5 resulted in a mixture of inward and outward currents mediated by a nonselective cation conductance and a calcium-activated potassium conductance (SK), respectively. A single injection of cocaine decreased the current activated by mGluR1 in dopamine neurons, and it had no effect on the size of the mGluR5-mediated current. When the injection of cocaine was preceded by treatment of the animals with a blocker of mGluR5 receptors (MPEP), cocaine no longer decreased the mGluR1 current. Thus, the activation of mGluR5 was required for the cocaine-mediated suppression of mGluR1-mediated currents in dopamine neurons. The results support the hypothesis that mGluR5 coordinates a reduction in mGluR1 functional activity after cocaine treatment.
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Paul F
authors.identifier: 0000000200953712
authors.initials: PF
authors.lastname: Kramer
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Williams
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology
chemical_list: D018765:Dopamine Uptake Inhibitors; D018683:Excitatory Amino Acid Agents; D026902:Potassium Channel Blockers; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D051640:Small-Conductance Calcium-Activated Potassium Channels; C104077:metabotropic glutamate receptor type 1; D008734:Methoxyhydroxyphenylglycol; D003042:Cocaine; C010117:3,4-dihydroxyphenylglycol
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