Understanding how alcohol and drugs of abuse affect the brain’s neuronal connections is vital to developing treatments for alcohol and drug use disorders. Tiffany Wills, Ph.D., Danny Winder, Ph.D., and colleagues are probing alcohol’s effects in the BNST, a brain region involved in stress-induced relapse.
The investigators studied normal and ethanol-related neuronal activity in the BNST in mice missing a subunit (GluN2B) of the glutamate NMDA receptor in this brain region. Deletion of GluN2B eliminated both a type of synaptic plasticity called long-term potentiation (LTP) and the actions of ethanol on NMDA receptor function. The researchers also showed that chronic ethanol exposure enhances LTP in the BNST, through an action on NMDA receptors in non-synaptic locations.
The studies, reported in the Proceedings of the National Academy of Sciences, demonstrate that the GluN2B subunit plays a key role – and that NMDA receptor localization is important – in plasticity and alcohol-related effects in the BNST. Therefore, therapeutic agents with subunit and/or localization specificity may be effective in preventing relapse in patients with alcohol use disorders.
This research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism and the National Institute of Mental Health.