RT Journal Article SR Electronic T1 Importance of the Noradrenaline–Dopamine Coupling in the Locomotor Activating Effects of d-Amphetamine JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 2729 OP 2739 DO 10.1523/JNEUROSCI.18-07-02729.1998 VO 18 IS 7 A1 Laurent Darracq A1 Gérard Blanc A1 Jacques Glowinski A1 Jean-Pol Tassin YR 1998 UL http://www.jneurosci.org/content/18/7/2729.abstract AB 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 α1-adrenergic antagonist (Blanc et al., 1994). 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 byd-amphetamine (2.0 mg/kg, i.p.), but it inhibits thed-amphetamine-induced locomotor hyperactivity (−63%,p < 0.0001). No behavioral activation occurred after the bilateral local perfusion of 3 μmd-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 μmd-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 systemicd-amphetamine for the behavioral effects to be elicited. Altogether, these results suggest that locomotor activating effects ofd-amphetamine are caused by the stimulation of cortical α1-adrenergic receptors by noradrenaline, which increases the release of a functional part of subcortical DA.