title: Control of extracellular dopamine at dendrite and axon terminals.
abstract: Midbrain dopamine neurons release dopamine from both axons and dendrites. The mechanism underlying release at these different sites has been proposed to differ. This study used electrochemical and electrophysiological methods to compare the time course and calcium dependence of somatodendritic dopamine release in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) to that of axonal dopamine release in the dorsal striatum. The amount of dopamine released in the striatum was approximately 20-fold greater than in cell body regions of the VTA or SNc. However, the calcium dependence and time to peak of the dopamine transients were similar. These results illustrate an unexpected overall similarity in the mechanisms of dopamine release in the striatum and cell body regions. To examine how diffusion regulates the time course of dopamine following release, dextran was added to the extracellular solution to slow diffusion. In the VTA, dextran slowed the rate of rise and fall of the extracellular dopamine transient as measured by fast-scan cyclic voltammetry yet did not alter the kinetics of the dopamine-dependent IPSC. Dextran failed to significantly alter the time course of the rise and fall of the dopamine transient in the striatum, suggesting a more influential role for reuptake in the striatum. The conclusion is that the time course of dopamine within the extracellular space of the VTA is dependent on both diffusion and reuptake, whereas the activation of D(2) receptors on dopamine neurons is primarily limited by reuptake.
authors.affiliation: Vollum Institute, Oregon Health & Science University L474, Portland, Oregon 97239, USA. fordc@ohsu.edu
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Ford
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Gantz
authors.forename: Paul E M
authors.initials: PE
authors.lastname: Phillips
authors.forename: John T
authors.initials: JT
authors.lastname: Williams
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001703:Biophysics / Q000379:methods; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007478:Iontophoresis / Q000379:methods; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000166:cytology
chemical_list: D003911:Dextrans; D018756:GABA Antagonists; D007211:Indoles; D010721:Phosphinic Acids; D011412:Propanolamines; C085075:CGP 55845A; D012701:Serotonin; D002118:Calcium; D004298:Dopamine; C000543:cyclopiazonic acid