PT  - JOURNAL ARTICLE
AU  - Wei-Xing Shi
AU  - Chen-Lun Pun
AU  - Xue-Xiang Zhang
AU  - Michelle D. Jones
AU  - Benjamin S. Bunney
TI  - Dual Effects of <span class="sc">d</span>-Amphetamine on Dopamine Neurons Mediated by Dopamine and Nondopamine Receptors
AID  - 10.1523/JNEUROSCI.20-09-03504.2000
DP  - 2000 May 01
TA  - The Journal of Neuroscience
PG  - 3504--3511
VI  - 20
IP  - 9
4099  - http://www.jneurosci.org/content/20/9/3504.short
4100  - http://www.jneurosci.org/content/20/9/3504.full
SO  - J. Neurosci.2000 May 01; 20
AB  - By increasing dopamine (DA) release and activating feedback mechanisms, amphetamine and related psychostimulants are known to inhibit DA cell firing. Here, we report that d-amphetamine also has an excitatory effect on DA cells, which under control conditions, is masked by the inhibitory effect ofd-amphetamine and is revealed when D2-like receptors are blocked. Thus, using in vivo single-unit recording in rats, we found that the selective D2 antagonist raclopride not only blocked the inhibition induced by d-amphetamine but also enabled d-amphetamine to excite DA cells. The excitation, expressed as an increase in both firing rate and bursting, persisted when both D1- and D2-like receptors were blocked by SCH23390 and eticlopride, suggesting that it is not mediated by DA receptors. The norepinephrine uptake blocker nisoxetine mimicked the effect ofd-amphetamine, especially the increase in bursting, whereas the 5-HT uptake blocker fluoxetine produced no significant effect. Adrenergic α1 antagonists prazosin and WB4101 and the nonselective α antagonist phenoxybenzamine completely blocked increase in bursting induced by d-amphetamine and partially blocked the increase in firing rate. The α2 antagonist idazoxan and the β antagonist propranolole, however, failed to prevent d-amphetamine from producing the excitation. Thus, revising the traditional concept, this study suggests that d-amphetamine has two effects on DA cells, a DA-mediated inhibition and a non-DA-mediated excitation. The latter is mediated in part through adrenergic α1 receptors.