Grant: CIHR Fellowship

Substance use causes over 180 million deaths and 6.8 million years of life lost annually worldwide. 21.6% of Canadians will suffer from drug addiction in their lifetime. Pharmacological treatment for addiction is a major unmet medical need. The few clinical treatments that exist are ineffective in preventing relapse. Lorcaserin is a drug that binds to, and activates a receptor in the brain (serotonin 2C). Lorcaserin has FDA approval as a treatment for obesity, and also has potential to treat addiction. Previous research has shown that lorcaserin can reduce drug taking and relapse in rats. This effect is likely caused by lorcaserin inhibiting a neurochemical (dopamine) implicated in relapse. Little else is known about the underlying brain areas associated with relapse, along with lorcaserin's ability to prevent it. Here, I propose to investigate the brain areas and activity patterns responsible for the prevention of cocaine use and relapse in rats conferred by lorcaserin. Rats will use levers to take cocaine and then stop drug use. Then, animals will be prompted to relapse by re-exposing them to cocaine. Animals will either be treated with lorcaserin or saline prior to relapse. During relapse I will take rats' brains and examine whether different areas are active during relapse, and when relapse is prevented by lorcaserin. I will use a machine (µPET) to detect where in the brain these neurochemicals are active. Finally I will quantify the neurochemical levels by sampling them from the brain using a method called microdialysis. I predict that relapse will increase activity, and dopamine levels in areas of the brain associated with drug rewards. Treatment with lorcaserin will block these effects and return brain activity to pre-relapse levels. This research is pivotal in understanding the underlying causes of relapse and will provide support for using lorcaserin as a treatment for drug addiction in humans.