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Review ArticleReview Article

Contrasting Regulation of Catecholamine Neurotransmission in the Behaving Brain: Pharmacological Insights from an Electrochemical Perspective

Megan E. Fox and R. Mark Wightman
Lynette C. Daws, ASSOCIATE EDITOR
Pharmacological Reviews January 2017, 69 (1) 12-32; DOI: https://doi.org/10.1124/pr.116.012948
Megan E. Fox
Department of Chemistry and Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina
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R. Mark Wightman
Department of Chemistry and Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina
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Lynette C. Daws
Department of Chemistry and Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina
Roles: ASSOCIATE EDITOR
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    Fig. 1.

    FSCV for the detection of catecholamines. The most commonly used waveform sweeps from −0.4 to +1.3 V at a scan rate of 400 V/s. The positive-going scan oxidizes dopamine and norepinephrine to their ortho-quinone form, and the negative-going scan reduces them back to dopamine or norepinephrine. Plotting the resultant current versus potential results in identical characteristic cyclic voltammograms (CVs) for both dopamine and norepinephrine.

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    Fig. 2.

    Spatially resolved measurements combined with pharmacology ensure either dopamine or norepinephrine measurements. Brain slice, adapted from the atlas of Paxinos and Watson showing norepinephrine terminals (red) surrounded by dopamine terminals (yellow), highlighting the need for a small sensor. Boxes show mock electrically stimulated response types to different drugs. Red bar denotes stimulation. In the green box, a pure dopamine signal increases with D2 antagonism and remains elevated with α2 antagonism; a pure norepinephrine signal does not increase following D2 antagonism and only responds to α2 antagonism. In the red box, a mixed dopamine/norepinephrine signal responds to both D2 and α2 antagonists. ac, anterior commissure; dBNST, dorsal bed nucleus of the stria terminalis; DS, dorsal striatum; VP, ventral pallidum.

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    TABLE 1

    Opposing catecholamine responses in awake animals

    Upward arrows reflect increases, and downward arrows reflect decreases in phasic release. Superscripted letters correspond to the following references. The literature cited in this table is meant to provide notable examples of contrasting signaling and is by no means comprehensive.

    StimulusNAc DopaminevBNST Norepinephrine
    At rest (transients)PresentaAbsentb
    ICSS
     Stimulation↑c↑d
     ICSS-predictive cue↑cNo effectd
     ICSS-extinction↓d↑d
    Food reward
     Unexpected food↑eNo effectf
     Food-predictive cue↑gUnknown
     Food omission↓hUnknown
    Drugs of abuse
     Drug exposure↑iNo effectj unknown
     Drug-predictive cue↑kUnknown
     Drug withdrawal↓j↑j, Unknown
    Noxious/Aversive
     Quinine↓l↑m
     Fear cues↑↓nUnknown
     Tail pinch↑↓o↑o
    • ↵a Robinson et al., 2001; Wightman et al., 2007; Sombers et al., 2009.

    • ↵b Park et al., 2012, 2013; Fox et al., 2016b.

    • ↵c Garris et al., 1999; Cheer et al., 2007a; Owesson-White et al., 2008.

    • ↵d Park et al., 2013.

    • ↵e Roitman et al., 2004, 2008; Cone et al., 2014.

    • ↵f Park et al., 2012.

    • ↵g Day et al., 2010; Brown et al., 2011; Cacciapaglia et al., 2012; McCutcheon et al., 2012; Saddoris et al., 2015b.

    • ↵h Saddoris et al., 2015a.

    • ↵i Budygin et al., 2001; Cheer et al., 2004; Heien et al., 2005; Aragona et al., 2008; Covey et al., 2014; Vander Weele et al., 2014; Fox et al., 2016b.

    • ↵j Fox et al., 2016b.

    • ↵k Phillips et al., 2003; Stuber et al., 2005; Cameron et al., 2014.

    • ↵l Roitman et al., 2008; Park et al., 2012; Twining et al., 2015.

    • ↵m Park et al., 2012.

    • ↵n Badrinarayan et al., 2012.

    • ↵o Park et al., 2015.

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Pharmacological Reviews: 69 (1)
Pharmacological Reviews
Vol. 69, Issue 1
1 Jan 2017
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Review ArticleReview Article

Contrasting Regulation of Catecholamines

Megan E. Fox and R. Mark Wightman
Pharmacological Reviews January 1, 2017, 69 (1) 12-32; DOI: https://doi.org/10.1124/pr.116.012948

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Review ArticleReview Article

Contrasting Regulation of Catecholamines

Megan E. Fox and R. Mark Wightman
Pharmacological Reviews January 1, 2017, 69 (1) 12-32; DOI: https://doi.org/10.1124/pr.116.012948
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  • Article
    • Abstract
    • I. Introduction
    • II. Building the Foundation for In Vivo Recordings
    • III. In Vivo Recordings in Anesthetized Animals
    • IV. Catecholamine Function in Awake Animals
    • V. Clinical Implications
    • VI. Summary
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