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Abstract
Benzodiazepines are commonly prescribed anxiolytics that pose abuse liability in susceptible individuals. Although it is well established that all drugs of abuse increase brain dopamine levels, and benzodiazepines are allosteric modulators of the GABAA receptor, it remains unclear how they alter dopamine release. Using in vivo fast-scan cyclic voltammetry, we measured diazepam-induced changes in the frequency and amplitude of transient dopamine release events. We found that diazepam concurrently increases the frequency and decreases the amplitude of transient dopamine release events in the awake and freely moving rat. The time course during which diazepam altered the frequency and amplitude of dopamine release events diverged, with the decreased amplitude effect being shorter lived than the increase in frequency, but both showing similar rates of onset. We conclude that diazepam increases the frequency of accumbal dopamine release events by disinhibiting dopamine neurons, but also decreases their amplitude. We speculate that the modest abuse liability of benzodiazepines is due to their ability to decrease the amplitude of dopamine release events in addition to increasing their frequency.
Footnotes
- Received March 29, 2017.
- Accepted October 4, 2017.
Funding for the project was provided by the National Institutes of Health [Grants R01DA031900 and R03DA038734], National Science Foundation [Grant IOS-1557755], a Boettcher Young Investigator Award, and a NARSAD Young Investigator Award.
The authors have no conflicts to disclose.
The work was previously presented as a poster presentation: Benzodiazpines and their dual administration with ethanol increase accumbal transient dopamine release events (2016) RAKOWSKI D R, SCHELP SA, BRODNIK Z, ESPAÑA RA, PULTORAK KJ, OLESON EB. The 2016 Society for Neuroscience Annual Meeting, San Diego, CA.
↵This article has supplemental material available at jpet.aspetjournals.org.
- Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
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