Grant: Project Grant

Opioid medications and street drugs are widely used and abused and have severe side-effects including respiratory depression that can be lethal with overdose. In Canada, the resulting opioid epidemic is a major health and socio-economic burden with tens of thousands of emergency visits and over 7,000 opioid-related deaths every year. Respiratory depression by opioids is due to abuse of street drugs like heroin, but equally due to abuse of prescription pain killers, which remain the pharmacological cornerstone of modern pain therapy. To identify solutions to the opioid epidemic, it is critical to identify the mechanisms of opioid-induced respiratory depression and analgesia. This research proposal aims to identify the brain circuits regulating respiratory depression and and analgesia by opioid drugs using a combination of neuroscience and respiratory physiology methodologies in rodents. Importantly, we aim to perform most of our experiments in freely-behaving rodents mimicking the complexity of opioid overdose in patients including loss of consciousness, respiratory distress, and analgesia. Our aims are to identify the brainstem circuits regulating opioid-induced respiratory depression in rodents and to pinpoint the midbrain circuits regulating breathing and nociception. Once the identity of these circuits is known, we aim to determine their role in respiratory depression and analgesia by opioid drugs. Our ultimate goal is to determine whether these neural circuits can be activated to prevent respiratory depression without reducing opioid analgesia, which may contribute to the development of new therapeutic solutions to the morbidity and mortality associated with opioid overdose.