Allosteric Modulation of GABAA Receptors in Rat Basolateral Amygdala Blocks Stress-Enhanced Reacquisition of Nicotine Self-Administration
- Burt M. Sharp*
- Qin JiangQin JiangDepartment of Genetics, Genomics and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Qin Jiang
- Xenia SimeoneXenia SimeoneDepartment of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, 1090, AustriaMore by Xenia Simeone
- , and
- Petra Scholze
Stress is a major determinant of relapse to smoked tobacco. In a rat model, repeated stress during abstinence from nicotine self-administration (SA) results in enhanced reacquisition of nicotine SA, which is dependent on the basolateral amygdala (BLA). We postulate that repeated stress during abstinence causes hyperexcitability of the BLA principal output neurons (PNs) due to disinhibition of the PNs from reduced inhibitory regulation by local GABAergic interneurons. To determine if enhanced GABAergic regulation of the BLA PNs can lessen the effects of stress on nicotine intake, positive allosteric modulators (PAMs) of GABAA receptors were infused into the BLA immediately prior to reacquisition of nicotine SA. Three selective PAMs [NS 16085 (binds the benzodiazepine site on α2/α3 GABAA); DCUK-OEt (binds a novel, benzodiazepine site on α1 or α5, β2 or β3, γ2 or δ GABAA); DS2 (binds exclusively to δ GABAA] with varied GABAA subunit specificities abolished the stress-induced amplification of nicotine taking during reacquisition. These studies indicate that highly selective PAMS targeting α3 or δ subunit-containing GABAA in the BLA may be effective in ameliorating the stress-induced relapse to smoked tobacco during abstinence from cigarettes.
Read this article
To access this article, please review the available access options below.
This article is cited by 1 publications.
- Andrew M. Novick, Korrina A. Duffy, Rachel L. Johnson, Mary D. Sammel, Wen Cao, Andrew A. Strasser, Mehmet Sofuoglu, Alexandra Kuzma, James Loughead, A. Leslie Morrow, C. Neill Epperson. Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone. Biology of Sex Differences 2022, 13