Grant: Operating Grant

Drugs of abuse, including nicotine from cigarette smoke and recreational or prescribed opioids for pain management (e.g. heroin or morphine) place a serious toll on the Heath Care System. These drugs directly depress the respiratory system which controls breathing and lead to impaired arousal responses, especially during sleep. One adverse effect in the newborn is failure of special cells in the body to detect a fall in blood oxygen or an increase in carbon dioxide leading to impaired arousal. These cells have sites for detecting naturally-occurring chemicals used for normal communication in the body. However, these same sites are targets for nicotine and opioid drugs. Importantly, the offspring of mothers who take these drugs during pregnancy can experience a high degree of morbidity and death, yet little is known about how these drugs work. We are interested in how these drugs affect special cells in the newborn animal, resulting in their inability to detect and respond appropriately to low oxygen and high carbon dioxide. We have developed an attractive model in the rat where these same cells malfunction when exposed to either nicotine or opioid drugs. Understanding the underlying cellular and molecular mechanisms is of central importance for developing effective therapeutic strategies. The goals of the present proposal are to uncover the mechanisms by which opioid exposure causes impaired detection of oxygen and carbon dioxide by these special cells in the newborn.