PT  - JOURNAL ARTICLE
AU  - Scott A. Schelp
AU  - Zachary D. Brodnik
AU  - Dylan R. Rakowski
AU  - Katherine J. Pultorak
AU  - Asha T. Sambells
AU  - Rodrigo A. España
AU  - Erik B. Oleson
TI  - Diazepam Concurrently Increases the Frequency and Decreases the Amplitude of Transient Dopamine Release Events in the Nucleus Accumbens
AID  - 10.1124/jpet.117.241802
DP  - 2018 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 145--155
VI  - 364
IP  - 1
4099  - http://jpet.aspetjournals.org/content/364/1/145.short
4100  - http://jpet.aspetjournals.org/content/364/1/145.full
SO  - J Pharmacol Exp Ther2018 Jan 01; 364
AB  - 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.