Altered hippocampal synaptic function in transgenic mice with increased astrocyte expression of CCL2 after withdrawal from chronic alcohol. (June 2018)

• Record Type: Journal Article
• Authors: Bray, Jennifer G.; Reyes, Kenneth C.; Roberts, Amanda J.; Gruol, Donna L.
• Is Part Of: Neuropharmacology. Volume 135(2018)
• Page Start: 113
• Page End: 125
• Publication Date: 2018-06
• Subjects: Two-bottle choice alcohol drinking -- Chronic intermittent alcohol exposure -- Hippocampus -- Synaptic plasticity -- Synaptic transmission -- Memory and learning; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2018.02.031
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: 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 ∼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. Highlights: CCL2/alcohol interactions alter hippocampal synaptic responses. CCL2/alcohol interactions alter hippocampal synaptic plasticity. CCL2/alcohol interactions vary across alcohol exposure paradigms.