Different Hypothalamic Nicotinic [alpha]7 Receptor Expression and Response to Low Nicotine Dose in Alcohol-Preferring and Alcohol-Avoiding Rats

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2016-02, Vol.40 (2), p.329
• Main Authors: Nuutinen, Saara, Panula, Pertti, Salminen, Outi
• Format: Article
• Language: English
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.12960

Background The aim of this study was to examine possible differences in nicotinic acetylcholine receptors and responses in rats with genetic preference or avoidance for alcohol. This was done by using 2 rat lines with high alcohol preference (Alko Alcohol [AA]) or alcohol avoidance (Alko Non-Alcohol [ANA]). Methods Locomotor activity was measured following nicotine and histamine H3 receptor (H3R) antagonist treatment. In situ hybridization and receptor ligand binding experiments were used in drug-naïve animals to examine the expression of different [alpha] nicotinic receptor subunits. Results The AA rats were found to be more sensitive to the stimulatory effect of a low dose of nicotine than ANA rats, which were not significantly activated. Combination of histamine H3R antagonist, JNJ-39220675, and nicotine resulted to similar locomotor activation as nicotine alone. To further understand the mechanism underlying the difference in nicotine response in AA and ANA rats, we studied the expression of [alpha]5, [alpha]6, and [alpha]7 nicotinic receptor subunits in specific brain areas of AA and ANA rats. We found no differences in the expression of [alpha]5 nicotinic receptor subunits in the medial habenula and hippocampus or in [alpha]6 subunit in the ventral tegmental area and substantia nigra. However, the level of [alpha]7 nicotinic receptor subunit mRNA was significantly lower in the tuberomamillary nucleus of posterior hypothalamus of alcohol-preferring AA rats than in alcohol-avoiding ANA rats. Also the hypothalamic [125]I-[alpha]-bungarotoxin binding was lower in AA rats indicating lower levels of [alpha]7 nicotinic receptors. Conclusions The lower expression and receptor binding of [alpha]7 nicotinic receptors in the tuberomamillary nucleus of AA rats suggest a difference in the regulation of brain histamine neurons between the rat lines since the [alpha]7 nicotinic receptors are located in histaminergic neurons. Stronger nicotine-induced locomotor response, mediated partially via [alpha]7 receptors, and previously described high alcohol consumption in AA rats could be explained by the found difference in tuberomamillary [alpha]7 receptor levels.