Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons.
Synchronous activation of dopamine neurons, for instance upon presentation of an unexpected rewarding stimulus, results in the release of dopamine from both terminals in projection areas and somatodendritic sites within the ventral midbrain. This report describes an inhibitory postsynaptic current (IPSC) that was elicited by dopamine in slices from mouse midbrain. The IPSC was tetrodotoxin sensitive, calcium dependent, and blocked by a D2 receptor antagonist. Inhibition of monoamine transporters prolonged the IPSC, indicating that the time course of dopamine neurotransmission is tightly regulated by reuptake. Changing the stimulus intensity altered the amplitude but not the time course of the IPSC, whose onset was faster than could be reproduced with iontophoresis. The results indicate a rapid rise in dopamine concentration at the D2 receptors, suggesting that dopamine that is released by a train of action potentials acts in a localized area rather than in a manner consistent with volume transmission.
Beckstead
Michael J
MJ
Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA.
Grandy
David K
DK
Wickman
Kevin
K
Williams
John T
JT
D000200:Action Potentials / Q000187:drug effects; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009943:Organophosphorus Compounds / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050637:Receptors, Dopamine D3; D012110:Reserpine / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D002121:Calcium Channel Blockers; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; C493594:Drd3 protein, mouse; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D007980:Levodopa; D013469:Sulpiride; C066430:CGP 35348; D012110:Reserpine; D003042:Cocaine; D002118:Calcium; D004298:Dopamine