The focus of the Behavioral Neurogenetics Laboratory is to understand the genetic basis of complex traits. We are specifically focused on the role of nicotinic acetylcholine receptors in both alcohol and nicotine use. To this end we use a vast array of approaches.
- Determine the effect of adolescent chronic social stress on later drug behaviors and neuronal function.
- Understand the influence of nicotinic acetylcholine receptors on alcohol behaviors.
- Identification of genetic variants in genes that code for nicotinic acetylcholine receptor subunits.
- Identification of genetic variants associated with alcohol and nicotine behaviors using statistical genetics approaches.
18-MC and Alcohol-Related Behaviors
This ongoing project seeks to determine the role of α3β4 nicotinic acetylcholine receptors in alcohol sensitization and stimulation. The project utilizes 18-Methoxycoronaridine (18-MC), an antagonist at α3β4 receptors. 18-MC is a derivative of the naturally occurring psychoactive substance Ibogaine. Ibogaine has been shown to treat opioid, stimulant, alcohol, and nicotine abuse but has been deemed unsafe for clinical use due to its side effects. 18-MC produces similar results with fewer side effects and a greater therapeutic index. We have previously found that 18-MC reduces binge-like ethanol consumption without altering the sedative effects of alcohol or consumption of sweet solutions. In the present study, adult DBA/2J mice receive an acute injection of 18-MC before testing for alcohol behaviors. Testing the effect that 18-MC has on alcohol-related behaviors will lead to a better understanding of how 18-MC reduces alcohol consumption and its ability to treat alcohol addiction.
Chronic Variable Social Stress and Morphine
This ongoing project explores how exposure to chronic variable social stress (CVSS) throughout adolescence affects morphine consumption, morphine sensitization, neuronal function, and gene expression in adulthood. Our working hypothesis is that exposure to adolescent stress will alter both behavior and physiology. Male and female C57BL/6J and BALB/cJ mice undergo CVSS during adolescence which involves repeated isolation and rehousing with novel cage-mates and are tested for morphine behaviors, electrophysiology, or gene expression in adulthood. By understanding how adolescent social stress alters morphine behaviors and gene expression, this may lead us to a greater understanding of what drives morphine dependence.
Varenicline, Alcohol Consumption, and Gene Expression
In recent years, varenicline(Chantix) has been shown to decrease ethanol consumption in adult rodents without affecting consumption of other sweet, rewarding solutions. Varenicline is a partial agonist at α4β2 nicotinic acetylcholine receptors, but has been shown to interact with other receptors at high concentrations. In order to gain a greater understanding of the mechanisms by which varenicline decreases ethanol consumption, we are performing RNA sequencing on striatal tissue from animals treated with varenicline or saline prior to an ethanol or water Drinking-in-the-Dark session. These results could identify novel candidate genes whose expression may contribute to the effects of varenicline on ethanol consumption.