title: Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data.
abstract: The neurotransmitter dopamine is heavily implicated in intracranial self-stimulation (ICSS). Many drugs of abuse that affect ICSS behavior target the dopaminergic system, and optogenetic activation of dopamine neurons is sufficient to support self-stimulation. However, the patterns of phasic dopamine release during ICSS remain unclear. Early ICSS studies using fast-scan cyclic voltammetry (FSCV) rarely observed phasic dopamine release, which led to the surprising conclusion that it is dissociated from ICSS. However, several advances in the sensitivity (i.e., the use of waveforms with extended anodic limits) and analysis (i.e., principal component regression) of FSCV measurements have made it possible to detect smaller, yet physiologically relevant, dopamine release events. Therefore, this study revisits phasic dopamine release during ICSS using these tools. It was found that the anodic limit of the voltammetric waveform has a substantial effect on the patterns of dopamine release observed during continuous ICSS. While data collected with low anodic limits (i.e., +1.0 V) support the disappearance of phasic dopamine release observed in previous investigation, the use of high anodic limits (+1.3 V, +1.4 V) allows for continual detection of dopamine release throughout ICSS. However, the +1.4 V waveform lacks the ability to resolve narrowly spaced events, with the best balance of temporal resolution and sensitivity provided by the +1.3 V waveform. Ultimately, it is revealed that the amplitude of phasic dopamine release decays but does not fully disappear during continuous ICSS.
authors.affiliation: Department of Chemistry and ‡Neuroscience Center and Neurobiology Curriculum, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-3290, United States.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Rodeberg
authors.affiliation: Department of Chemistry and ‡Neuroscience Center and Neurobiology Curriculum, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-3290, United States.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Department of Chemistry and ‡Neuroscience Center and Neurobiology Curriculum, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-3290, United States.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Bucher
authors.affiliation: Department of Chemistry and ‡Neuroscience Center and Neurobiology Curriculum, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-3290, United States.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wightman
mesh_terms: D000818:Animals; D057219:Biofouling; D002408:Catheters, Indwelling; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D058542:Implantable Neurostimulators; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation / Q000502:physiology*; D013997:Time Factors
chemical_list: D004298:Dopamine
keywords: Dopamine; intracranial self-stimulation; kinetics; voltammetry