The Journal of Neuroscience, January 1, 2001, 21(1):35-44
Characterization of Extracellular Dopamine Clearance in the
Medial Prefrontal Cortex: Role of Monoamine Uptake and Monoamine
Oxidase Inhibition
Hollie K.
Wayment1,
James O.
Schenk1, 2, 3, and
Barbara A.
Sorg3, 4
Departments of 1 Chemistry and
2 Biochemistry and Biophysics, and 3 Program in
Neuroscience and 4 Department of Veterinary and Comparative
Anatomy, Pharmacology and Physiology, Washington State University,
Pullman, Washington 99164
In vitro rotating disk electrode (RDE) voltammetry
and in vivo microdialysis were used to characterize
dopamine clearance in the rat medial prefrontal cortex (mPFC). RDE
studies indicate that inhibition by cocaine, specific inhibitors of the
dopamine transporter (DAT) and norepinephrine transporter (NET), and
low Na+ produced a 50-70% decrease in the velocity
of dopamine clearance. Addition of the monoamine (MAO) inhibitors,
L-deprenyl, clorgyline, pargyline, or in
vivo nialamide produced 30-50% inhibition. Combined effects
of uptake inhibitors with L-deprenyl on dopamine clearance were additive (up to 99% inhibition), suggesting that at least two
mechanisms may contribute to dopamine clearance. Dopamine measured
extracellularly 5 min after exogenous dopamine addition to incubation
mixtures revealed that most conditions of DAT/NET inhibition did not
produce elevated dopamine levels above controls. Inhibition of MAO
produced elevated dopamine levels only after long-term, but not
short-term, incubation in vitro. Short-term incubation of L-deprenyl combined with DAT and NET uptake
inhibitors increased dopamine above control levels, consistent with
more than one mechanism of dopamine clearance. Local infusion of
pargyline (100 or 300 µM) into the mPFC or striatum via
microdialysis produced more pronounced and immediate increases in mPFC
dopamine levels compared with striatum. Furthermore, dopamine elevation
in the mPFC was not accompanied by a decrease in the dopamine
metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, as
found in the striatum. These findings may have revealed a unique
mechanism of mPFC dopamine clearance and therefore contribute to the
understanding of multiple behaviors that involve mPFC dopamine
transmission, such as schizophrenia, drug abuse, and working memory function.
Key words:
dopamine; cocaine; dopamine transporter; medial
prefrontal cortex; monoamine oxidase; rotating disk electrode
voltammetry
Copyright © 2001 Society for Neuroscience 0270-6474/01/21135-10$05.00/0
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