The Journal of Neuroscience, May 15, 1999, 19(10):4123-4131
Opposing Role of Dopamine D1 and D2 Receptors in Modulation of
Rat Nucleus Accumbens Noradrenaline Release
Louk J. M. J.
Vanderschuren,
George
Wardeh,
Taco J.
De Vries,
Arie
H.
Mulder, and
Anton N. M.
Schoffelmeer
Research Institute Neurosciences Vrije Universiteit, Department of
Pharmacology, Medical Faculty, Free University, Amsterdam, The
Netherlands
The role of dopamine receptors in the modulation of nucleus
accumbens noradrenaline release was investigated in superfused rat
brain slices. At concentrations of 
1 µM, dopamine
enhanced, whereas at higher concentrations dopamine inhibited
electrically evoked [3H]noradrenaline
release. The D1 receptor agonist SKF-38393 increased, whereas
the D2 agonist quinpirole inhibited evoked
[3H]noradrenaline release. These effects were
attenuated by the D1 antagonist SCH-23390 and the D2 antagonist
(
)-sulpiride, respectively, indicating that accumbens noradrenaline
release is regulated by stimulatory D1 and inhibitory D2 receptors.
Whereas ()-sulpiride enhanced, SCH-23390 did not reduce evoked
accumbens [3H]noradrenaline release, indicating a
tonic activation of D2 receptors only. Given the similar apparent
affinity of dopamine for D1 and D2 receptors in striatal slices, the
lack of tonic D1 receptor activation suggests that D1, unlike D2,
receptors are extrasynaptically localized. No dopaminergic modulation
of noradrenaline release was observed in rat medial prefrontal cortex
or amygdala slices. To examine the regulation of accumbens
noradrenaline release under conditions of increased dopaminergic
activity, measurements were made using slices of amphetamine-pretreated
rats. In these slices, the electrically evoked release of
[3H]dopamine and
[3H]noradrenaline was enhanced. The increasing
effect of ()-sulpiride on noradrenaline release was augmented, and
SCH-23390 almost completely reversed this enhancement of
[3H]noradrenaline release. These data suggest that
whereas although under a moderate dopaminergic tone, accumbens
noradrenaline release is mainly regulated by inhibitory D2 receptors,
under circumstances of increased dopaminergic activity, recruitment of
extrasynaptic stimulatory D1 receptors contributes to enhancement of
noradrenaline release.
Key words:
noradrenaline release; nucleus accumbens; dopamine
release; dopamine D1 receptor; dopamine D2 receptor; amphetamine
Copyright © 1999 Society for Neuroscience 0270-6474/99/19104123-09$05.00/0
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