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• W2893324537 endingPage "1985" @default.
• W2893324537 startingPage "1978" @default.
• W2893324537 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." @default.
• W2893324537 created "2018-10-05" @default.
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• W2893324537 date "2018-09-25" @default.
• W2893324537 modified "2023-10-01" @default.
• W2893324537 title "Local GABA_A Receptor-Mediated Suppression of Dopamine Release within the Nucleus Accumbens" @default.
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• W2893324537 doi "https://doi.org/10.1021/acschemneuro.8b00268" @default.
• W2893324537 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30253088" @default.
• W2893324537 hasPublicationYear "2018" @default.
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