Opposing effects of ethanol and nicotine on hippocampal calbindin-D28k expression

• Published in: Alcohol (Fayetteville, N.Y.) Vol. 31; no. 1-2; pp. 1 - 10
• Main Authors: MULHOLLAND, Patrick J, HARRIS, Barton R, WILKINS, Lincoln H, SELF, Rachel L, BLANCHARD, John A, HOLLEY, Robert C, LITTLETON, John M, PRENDERGAST, Mark A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01.08.2003
• Subjects: Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Calbindin 1; Calbindins; Dose-Response Relationship, Drug; Ethanol - pharmacology; Female; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Hippocampus - chemistry; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medical sciences; Nicotine - pharmacology; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein G - analysis; S100 Calcium Binding Protein G - biosynthesis; Substance Withdrawal Syndrome - metabolism; Tobacco, tobacco smoking; Toxicology; Poison withdrawal; Calcium; Ethanol; Rat; Withdrawal; Alcoholism; Rodentia; Neuroloxicity; Vertebrata; Mammalia; Animal; Calbindin-D28k; Disintoxication; Nicotine
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2003.09.001

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.