Preclinical translation of NE in alcoholism

Noradrenergic stress mechanisms in alcoholism: Preclinical translation and drug repurposing

University of Wisconsin, Office of the Vice Chancellor for Research and Graduate Education
John Curtin (PI)
Direct costs: $36,097
Status: Completed. 07/2015 – 06/2016

Neuroscience evidence suggests that noradrenergic neurotransmission within the central nervous system partially mediates defensive reactivity to stressors. Stressors contribute strongly to drug use and relapse among human drug dependent users. Stress-induced reinstatement is a well-validated animal model of addiction and alpha-1 noradrenergic receptor (NE-α1) antagonists reduce relapse in this model. As such, the use of NE-α1 antagonists to reduce the response to stressors appears to be a very promising form of relapse prevention in addiction.

We propose to conduct a study to implicate NE stress mechanisms in humans via direct pharmacological antagonism of the NE system by doxazosin (an NE-α1 antagonist) in a validated stress task. Furthermore, we will test doxazosin’s ability to ameliorate the exaggerated stress response in alcoholics during early abstinence. This research represents a cost-effective first step to repurpose the use of NE-α1 antagonists to treat alcoholism.