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The Journal of Neuroscience, April 1, 1998, 18(7):2729-2739
Importance of the Noradrenaline-Dopamine Coupling in the
Locomotor Activating Effects of D-Amphetamine
Laurent
Darracq,
Gérard
Blanc,
Jacques
Glowinski, and
Jean-Pol
Tassin
Institut National de la Santé et de la Recherche
Médicale U114, Collège de France, 75231 Paris Cedex 05, France
The locomotor hyperactivity induced by systemic or local (nucleus
accumbens) D-amphetamine injections can be blocked by
systemic or local (prefrontal cortex) injections of prazosin, an
 1-adrenergic antagonist (). Microdialysis studies
performed on freely moving animals indicated that prazosin (0.5 mg/kg,
i.p.) does not modify the increase in the extracellular dopamine (DA) levels in the nucleus accumbens that are induced by
D-amphetamine (2.0 mg/kg, i.p.), but it inhibits the
D-amphetamine-induced locomotor hyperactivity ( 63%,
p < 0.0001). No behavioral activation occurred after the bilateral local perfusion of 3 µM
D-amphetamine in the nucleus accumbens, although it led to
a fivefold increase in extracellular DA levels. This increase in
extracellular DA levels was not affected by prazosin (0.5 mg/kg, i.p.).
When an intraperitoneal injection of D-amphetamine (0.5 mg/kg) was superimposed to the continuous local perfusion of 3 µM D-amphetamine, it induced a 64% increase in the extracellular DA levels in the nucleus accumbens, and this response was associated with simultaneous behavioral activation. Both
the increases in extracellular DA levels and in locomotor activity were
completely blocked by a pretreatment with prazosin, injected either
systemically (0.5 mg/kg, i.p.) or locally and bilaterally into the
prefrontal cortex (500 pmol/side). Complementary experiments indicated
that the focal application of D-amphetamine requires at
least a 4.8-fold higher increase in DA output compared with systemic
D-amphetamine for the behavioral effects to be elicited. Altogether, these results suggest that locomotor activating effects of
D-amphetamine are caused by the stimulation of cortical
1-adrenergic receptors by noradrenaline, which increases the release
of a functional part of subcortical DA.
Key words:
NA-DA coupling; D-amphetamine; prazosin; locomotor activity; prefrontal cortex; nucleus accumbens; microdialysis; 1-adrenergic receptors
Copyright © 1998 Society for Neuroscience 0270-6474/98/1872729-11$05.00/0
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