Examining the role of α6β2* nicotinic acetylcholine receptors on ethanol-induced behavioral responses in adolescent C57BL/6J mice
Open Access
- Graduate Program:
- Molecular, Cellular and Integrative Biosciences
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- November 09, 2015
- Committee Members:
- Helen Kamens, Thesis Advisor
- Keywords:
- Ethanol
- nicotinic acetylcholine receptors
- adolescence
- mice
- bPiDI
- consumption
- ataxia
- sedation
- Abstract:
- Alcohol and nicotine are two of the most commonly abused substances. Prior studies have shown that they share common genes and mechanisms that underlie their reinforcing properties in the dopaminergic (DA) neurons of the ventral tegmental area (VTA). The system of interest that modulates reward behavior is the mesolimbic dopamine system, which includes the VTA, the nucleus accumbens (NAc) and DA neurons. The primary targets for nicotine are neuronal nicotinic acetylcholine receptors (nAChRs) which are found throughout the brain. Studies have suggested that alcohol may be interacting with these receptors directly or indirectly along with nicotine, thus giving a possible mechanism for the co-use of these two substances. In particular, the α6β2* nAChRs are highly expressed within the ventral tegmental area on dopaminergic neurons. Due to the localization of these receptors, researchers have begun to isolate this subset for its possible involvement in modulating alcohol-induced behaviors. In this study, we examined the role of α6β2* receptors in ethanol-induced behaviors by using the antagonist N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI), a drug that specifically targets α6β2* receptors. In brief, adolescent age C57BL/6J mice were subjected to treatments of saline, 10, 15, 20 or 25 mg/kg doses of bPiDI before being tested in several behavioral experiments: locomotor activity, ethanol consumption, ataxia and sedation. In our locomotor activity studies, bPiDI significantly decreased locomotor activity for specific doses and times during testing in male and female adolescent mice where female mice had higher locomotor activity throughout the experiment in comparison to males. Male and female adolescent mice had initial decreases in ethanol consumption at the highest dose of bPiDI. Initial decreases in tastant consumption for higher doses of bPiDI in male and female mice revealed that the effects on EtOH were not specific to EtOH-mediated effects. The influence of bPiDI on ataxia and sedation were not observed in the experiments reported here for both sexes. The data presented here provide evidence for the involvement of α6β2* nAChRs in modulating locomotor activity and EtOH consumption.