Dual Effects of d-Amphetamine on Dopamine Neurons Mediated by Dopamine and Nondopamine Receptors

Journal of Neuroscience - Tập 20 Số 9 - Trang 3504-3511 - 2000
Wei‐Xing Shi1, Chen‐Lun Pun1, Xuexiang Zhang1, M. D. Jones1, Benjamin S. Bunney1
1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510

Tóm tắt

By increasing dopamine (DA) release and activating feedback mechanisms, amphetamine and related psychostimulants are known to inhibit DA cell firing. Here, we report thatd-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, usingin vivosingle-unit recording in rats, we found that the selective D2 antagonist raclopride not only blocked the inhibition induced byd-amphetamine but also enabledd-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 byd-amphetamine and partially blocked the increase in firing rate. The α2 antagonist idazoxan and the β antagonist propranolole, however, failed to preventd-amphetamine from producing the excitation. Thus, revising the traditional concept, this study suggests thatd-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.

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Journal of Neuroscience

Tập 20 Số 9

3504-3511

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