Grant: CIHR Fellowship

Opioid use disorder (OUD) affects over 16 million people over the world and is responsible for over 120,000 deaths yearly. It has become one of the worst public health disasters in Canada and the United States, and despite this, there are no effective long-term treatments available for addiction. A hallmark of drug abuse is continued drug intake despite negative consequences, which underlies repeated drug use and addiction. This can be modelled well in mice by pairing drug intake with a negative consequence (such as a foot shock). While most mice will stop taking opioids when they are punished (punishment-sensitive; PS) a subset will continue despite the foot shock (punishment-resistant; PR). We propose to use these existing differences to discover changes in brain cells that may underlie PS and PR drug use. Long-term changes in a brain area called the ventral pallidum (VP) are responsible for drug use, however, little is known about what exactly these changes are, and what type of brain cells are involved. A specific population of cells in the VP (VPGlu) are known to stop rewarding behaviors, such as drug use, in the face of negative consequences. Therefore, it is possible that these cells could be involved in stopping opioid intake as well. We will first investigate whether VPGlu are activated in mice during opioid intake that is paired with a punishment. Next, we will investigate how VPGlu are different between PS and PR mice. We expect that VPGlu in PS mice function to stop opioid intake when faced with punishment. However, we propose that VPGlu in PR mice are less active, resulting in punishment resistance. Together, these experiments will reveal the role of VPGlu in opioid abuse, and determine how VPGlu are different in mice that are PS and PR. We hope our work will help prevent and treat OUD by identifying new targets for the treatment of OUD, and at the same time, be used to predict if someone will be prone to addiction in the future.