title: Opposing effects of ethanol and nicotine on hippocampal calbindin-D28k expression.
abstract: Long-term ethanol exposure produces multiple neuroadaptations that likely contribute to dysregulation of Ca(2+) balance and neurotoxicity during ethanol withdrawal. Conversely, nicotine exposure may reduce the neurotoxic consequences of Ca(2+) dysregulation, putatively through up-regulation of the Ca(2+)-buffering protein calbindin-D(28k). The current studies were designed to examine the extent to which 10-day ethanol exposure and withdrawal altered calbindin-D(28k) expression in rat hippocampus. Further, in these studies, we examined the ability of nicotine, through action at alpha(7)(*)-bearing nicotinic acetylcholine receptors (nAChRs), to antagonize the effects of ethanol exposure on calbindin-D(28k) expression. Organotypic cultures of rat hippocampus were exposed to ethanol (50-100 mM) for 10 days. Additional cultures were exposed to 500 nM (-)-nicotine with or without the addition of 50 mM ethanol, 100 nM methyllycaconitine (an alpha(7)*-bearing nAChR antagonist), or both. Prolonged exposure to ethanol (>/=50 mM) produced significant reductions of calbindin-D(28k) immunolabeling in all regions of the hippocampal formation, even at nontoxic concentrations of ethanol. Calbindin-D(28k) expression levels returned to near-control levels after 72 h of withdrawal from 10-day ethanol exposure. Extended (-)-nicotine exposure produced significant elevations in calbindin-D(28k) expression levels that were prevented by methyllycaconitine co-exposure. Co-exposure of cultures to (-)-nicotine with ethanol resulted in an attenuation of ethanol-induced reductions in calbindin-D(28k) expression levels. These findings support the suggestion that long-term ethanol exposure reduces the neuronal capacity to buffer accumulated Ca(2+) in a reversible manner, an effect that likely contributes to withdrawal-induced neurotoxicity. Further, long-term exposure to (-)-nicotine enhances calbindin-D(28k) expression in an alpha(7)* nAChR-dependent manner and antagonizes the effects of ethanol on calbindin-D(28k) expression.
authors: Department of Psychology, University of Kentucky, 115 Kastle Hall, Lexington, KY 40506-0044, USA.
authors: Patrick J
authors: PJ
authors: Mulholland
authors: Barton R
authors: BR
authors: Harris
authors: Lincoln H
authors: LH
authors: Wilkins
authors: Rachel L
authors: RL
authors: Self
authors: John A
authors: JA
authors: Blanchard
authors: Robert C
authors: RC
authors: Holley
authors: John M
authors: JM
authors: Littleton
authors: Mark A
authors: MA
authors: Prendergast
mesh_terms: D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000032:analysis / Q000096:biosynthesis*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
chemical_list: C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D000431:Ethanol; D009538:Nicotine