| Amphetamine paradoxically augments exocytotic dopamine release and phasic dopamine signals. | |
| | |
MedLine Citation:
|
PMID: 23303926 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Drugs of abuse hijack brain-reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting nonexocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties, which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to 2 h. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration, and frequency of spontaneous dopamine transients, the naturally occurring, nonelectrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sugar reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sugar-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify upregulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. |
| | |
Authors:
|
D P Daberkow; H D Brown; K D Bunner; S A Kraniotis; M A Doellman; M E Ragozzino; P A Garris; M F Roitman |
Related Documents
:
|
9595856 - Composition of the cerebral white matter sterol ester fraction in severe experimental h... 20153736 - Hypoxic preconditioning provides neuroprotection and increases vascular endothelial gro... 10841376 - Hypoxia influences enkephalin release in rats. 20635216 - Prevention of neurodegenerative damage to the brain in rats in experimental alzheimer's... 23463336 - Effects of dried citrus unshiu peels on gastrointestinal motility in rodents. 16980916 - Pneumococcal meningitis threshold model: a potential tool to assess infectious risk of ... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 33 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
|
Languages: eng Pagination: 452-63 Citation Subset: IM |
Affiliation:
|
School of Biological Sciences, Cell Biology, Physiology and Development Section, Illinois State University, Normal, Illinois 61790, and Department of Psychology, University of Illinois at Chicago, Chicago, Illinois 60607. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Synchronization of medial temporal lobe and prefrontal rhythms in human decision making.
Next Document: Melanocortin-4 Receptor Regulates Hippocampal Synaptic Plasticity through a Protein Kinase A-Depende...