Journal article
Local GABAA Receptor-Mediated Suppression of Dopamine Release within the Nucleus Accumbens
ACS chemical neuroscience, v 10(4), pp 1978-1985
17 Apr 2019
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Benzodiazepines make up a class of psychoactive drugs that act as allosteric co-activators of the inhibitory GABAA receptor. These drugs are useful for the treatment of several psychiatric disorders but also hold considerable abuse liability. Despite the common use and misuse of benzodiazepines, the mechanisms through which these drugs exert their reinforcing effects remain incompletely understood. Transient phasic increases in dopamine levels are believed to play an important role in defining the reinforcing properties of drugs of abuse, and we recently demonstrated that systemic administration of benzodiazepines increased the frequency of these events but concomitantly reduced their amplitude. This observation provides insight into the pharmacological effects of benzodiazepines on dopamine signaling, but the processes through which benzodiazepines drive changes in phasic dopamine signals remain unclear. In these studies, we investigated the mechanisms through which benzodiazepines may reduce the phasic dopamine transient amplitude. We tested the effect of the benzodiazepine diazepam and the GABAA agonist muscimol on evoked dopamine release from nucleus accumbens brain slices using fast scan cyclic voltammetry. We found that both diazepam and muscimol reduce dopamine release and that reductions in dopamine release following GABAA receptor activation can be blocked by co-application of a GABAB receptor antagonist. These results suggest that activation of GABAA receptors in the nucleus accumbens decreases dopamine release by disinhibition of local GABA signaling and subsequent activation of GABAB receptors. Overall, this work provides a putative mechanism through which benzodiazepines reduce the amplitude of phasic dopamine release in vivo.
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Details
- Title
- Local GABAA Receptor-Mediated Suppression of Dopamine Release within the Nucleus Accumbens
- Creators
- Zachary D Brodnik - Drexel UniversityAashita Batra - Drexel UniversityErik B Oleson - University of Colorado DenverRodrigo A España - Drexel University
- Publication Details
- ACS chemical neuroscience, v 10(4), pp 1978-1985
- Publisher
- American Chemical Society; Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000465189200016
- Scopus ID
- 2-s2.0-85054846829
- Other Identifier
- 991019167619204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Medicinal
- Neurosciences