In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 20, No. 9 ( 2000-05-01), p. 3504-3511
Abstract:
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 of d -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 of d -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.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.20-09-03504.2000
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2000
detail.hit.zdb_id:
1475274-8
detail.hit.zdb_id:
604637-X
SSG:
12
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