Varenicline and nicotine enhance GABAergic synaptic transmission in rat CA1 hippocampal and medial septum/diagonal band neurons

LIFE SCIENCES

卷:92

Article

DuBois, Dustin W.¹  Damborsky, Joanne C.¹  Fincher, Annette S.¹  Frye, Gerald D.¹  Winzer-Serhan, Ursula H.¹ 

[1] Texas A&M Syst Hlth Sci Ctr, Dept Neurosci & Expt Therapeut, Coll Med, Bryan, TX 77807 USA

关键词: Addiction;    Dependence;    Cognitive function;    GABA release;    mIPSC;    Basal forebrain;    Hippocampus;   

DOI  :  10.1016/j.lfs.2012.12.013

来源: Elsevier

【 摘 要 】

Aims: The FDA approved smoking cessation aid varenicline can effectively attenuate nicotine-stimulated dopamine release. Varenicline may also exert important actions on other transmitter systems that also influence nicotine reinforcement or contribute to the drug's cognitive and affective side effects. In this study, we determined if varenicline, like nicotine, can stimulate presynaptic GABA release. Main methods: Using whole-cell patch-clamp techniques, we measured GABA(A)R-mediated asynchronous, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in acute brain slices from two brain regions important for learning and memory, the hippocampus and basal forebrain. Key findings: Both varenicline (10 mu M) and nicotine (10 mu M) applications alone resulted in small but significant increases in amplitude, as well as robustly enhanced frequency of mIPSCs in hippocampal CA1 pyramidal neurons and medial septum/diagonal band (MS/DB) neurons. A unique subpopulation of MS/DB neurons showed decreases in frequency. In the presence of nicotine, varenicline effectively attenuated the expected enhancement of hippocampal mIPSC frequency like a competitive antagonist. However, in the MS/DB, varenicline only partially attenuated nicotine's effects. Reversing the order of drug application by adding nicotine to varenicline-exposed slices had little effect. Significance: Varenicline, like nicotine, stimulates presynaptic GABA release, and also exerts a partial agonist action by attenuating nicotine-stimulated release in both the hippocampus and basal forebrain. These effects could potentially affect cognitive functions. (c) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

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