Background: Prior studies demonstrate that ethanol (EtOH) exposure induces the release of intracellular calcium (CA2+) in modulation of γ-aminobutyric acid-ergic tone and produces concomitant alterations in sigma (σ)-1 protein expression that may contribute to the development EtOH dependence. However, the influence of CA2+ released from endoplasmic reticulum (ER)-bound inositol triphosphate (IP3) and σ-1 receptors in regulating hippocampal function has yet to be delineated. Methods: Rat hippocampal explants were subjected to chronic intermittent EtOH (CIE) exposure with or without the addition of IP3 inhibitor xestospongin C (0 to 0.5 μM) or σ-1 receptor antagonist BD-1047 (0 to 80 μM). Hippocampal viability was assessed via immunohistochemical labeling of neuron-specific nuclear protein (NeuN)/Fox-3 in CA1, CA3, and dentate gyrus (DG) subregions. Results: Exposure to CIE produced consistent and significant decreases of NeuN/Fox-3 in each primary cell layer of the hippocampal formation. Co-exposure to xestospongin reversed these effects in the CA1 subregion and significantly attenuated these effects in the CA3 and DG regions. Xestospongin application also significantly increased NeuN/Fox-3 immunofluorescence in EtOH-naïve hippocampi. Co-exposure to 20 μM BD-1047 also reversed the loss of NeuN/Fox-3 during CIE exposure in each hippocampal cell layer, whereas exposure to 80 μM BD-1047 did not alter NeuN/Fox-3 in EtOH-treated hippocampi. By contrast, 80 μM BD-1047 application significantly increased NeuN/Fox-3 immunofluorescence in EtOH-naïve hippocampi in each subregion. Conclusions: These data suggest that EtOH stimulates ER IP3 and σ-1 receptors to promote hippocampal loss of NeuN/Fox-3 during CIE.
|Number of pages||8|
|Journal||Alcoholism: Clinical and Experimental Research|
|State||Published - Jul 1 2016|
Bibliographical noteFunding Information:
This research was supported by AA013388 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) awarded to MAP and T32 DA035200 awarded to ARR from the National Institute on Drug Abuse (NIDA). The authors have no conflicts of interest to declare.
Copyright © 2016 by the Research Society on Alcoholism
- Ethanol Withdrawal
- Inositol Triphosphate
- Neuron-Specific Nuclear Protein
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Psychiatry and Mental health