Altered hippocampal synaptic function in transgenic mice with increased astrocyte expression of CCL2 after withdrawal from chronic alcohol

NEUROPHARMACOLOGY

卷:135

Article

Bray, Jennifer G.^1,2  Reyes, Kenneth C.¹  Roberts, Amanda J.¹  Gruol, Donna L.¹ 

[1] Scripps Res Inst, Mol & Cellular Neurosci Dept, La Jolla, CA 92037 USA

[2] Univ Wisconsin, Dept Biol, Stevens Point, WI 54481 USA

关键词: Two-bottle choice alcohol drinking;    Chronic intermittent alcohol exposure;    Hippocampus;    Synaptic plasticity;    Synaptic transmission;    Memory and learning;   

DOI  :  10.1016/j.neuropharm.2018.02.031

来源: Elsevier

【 摘 要 】

CNS actions of the chemokine CCL2 are thought to play a role in a variety of conditions that can have detrimental consequences to CNS function, including alcohol use disorders. We used transgenic mice that express elevated levels of CCL2 in the CNS (CCL2-tg) and their non-transgenic (non-tg) littermate control mice to investigate long-term consequences of CCL2/alcohol/withdrawal interactions on hippocampal synaptic function, including excitatory synaptic transmission, somatic excitability, and synaptic plasticity. Two alcohol exposure paradigms were tested, a two-bottle choice alcohol (ethanol) drinking protocol (2BC drinking) and a chronic intermittent alcohol (ethanol) (CIE/2BC) protocol. Electrophysiological measurements of hippocampal function were made ex vivo, starting similar to 0.6 months after termination of alcohol exposure. Both alcohol exposure/withdrawal paradigms resulted in CCL2-dependent interactions that altered the effects of alcohol on synaptic function. The synaptic alterations differed for the two alcohol exposure paradigms. The 2BC drinking/withdrawal treatment had no apparent long-term consequences on synaptic responses and long-term potentiation (LTP) in hippocampal slices from non-tg mice, whereas synaptic transmission was reduced but LTP was enhanced in hippocampal slices from CCL2-tg mice. In contrast, the CIE/2BC/withdrawal treatment enhanced synaptic transmission but reduced LTP in the non-tg hippocampus, whereas there were no apparent long-term consequences to synaptic transmission and LTP in hippocampus from CCL2-tg mice, although somatic excitability was enhanced. These results support the idea that alcohol-induced CCL2 production can modulate the effects of alcohol exposure/withdrawal on synaptic function and indicate that CCL2/alcohol interactions can vary depending on the alcohol exposure/withdrawal protocol used. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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