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Role of α3 subunit‐containing GABA A receptors in benzodiazepine (BZ)‐related anti‐conflict, reinforcing, and cognitive effects
Author(s) -
Meng Zhiqiang,
Sawyer Eileen K,
Poe Michael,
Wang Zhijian,
Cook James M,
Rowlett James K
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.661.1
Subject(s) - anxiolytic , gabaa receptor , benzodiazepine , cognition , alprazolam , receptor , anxiety , pharmacology , effects of sleep deprivation on cognitive performance , neuroscience , psychology , medicine , psychiatry
Benzodiazepine (BZ)‐type drugs are effective in treating many disorders. However, their therapeutic use is limited by unwanted side effects including abuse potential, physical dependence, and cognitive deficits. BZ‐type drugs act by binding to GABA A receptors and facilitate the effects of GABA. As there are multiple subtypes of GABA A receptors, it may be possible to attribute the therapeutic effects and side effects of BZs to different subtypes. Here, we evaluated the behavioral effects of YT‐III‐31, a novel compound which exhibits selective efficacy at α3 subunit‐containing GABA A receptors, in rhesus monkeys. We first evaluated its anti‐anxiety effects using a conflict procedure. Pretreatment of YT‐III‐31 failed to produce robust anxiolytic effects. We then tested the reinforcing effects of YT‐III‐31 by using a progressive ratio self‐administration procedure. Significant reinforcing effects compared to vehicle control were found. Finally, we examined its effects on cognitive tasks. Using an intradimensional/extradimensional attentional set‐shift task, we found that YT‐III‐31 impaired performance similar to the reference BZ, alprazolam. Together, these results suggest that α3‐GABA A receptors play important roles in BZ‐related reinforcing effects and cognitive‐impairing effects, but not the anxiolytic effects. Funding: DA011792 , DA033795 , AG03536, MH046851 , and OD011103