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Dennis D. Rasmussen PhD Research Professor drasmuss@u.washington.edu Fax: (206) 768-5456 Site: VA Puget Sound Health Care System VAPSHCS 1660 S. Columbian Way, (S-116 ATC) Box 358280 Seattle, WA 98108 Link to CV

Bio Alcohol Effects on Opiomelanocortinergic Regulation This investigation addresses the roles that forebrain and pituitary opiomelanocortinergic systems may play in mediating responses to ethanol; the primary focus is the role of the endogenous opioid peptide, beta-endorphin. We use the rat as a model. This investigation is supported by a grant from NIAAA/NIH. Melatonin Replacement During Aging: Effects On Brain Opiomelanocortinergic Regulation Forebrain opiomelanocortinergic activity declines with aging and this decline in brain opioid activity has been suggested to medicate varied aging-associated neuroendocrine changes. Pineal melatonin secretion also declines with aging and melatonin supplementation has been suggested to have a wide variety of beneficial "anti-aging" effects. There is evidence that some of these effects of melatonin replacement may be mediated by increasing forebrain dopaminergic and endogenous opioid activity. We are investigating the effect of nightly melatonin supplementation throughout aging on forebrain dopaminergic and opiomelanocortinergic activity in the rat. Neuroendocrine therapy of alcohol abuse We are using the hormone melatonin to reverse changes in brain and neuroendocrine regulation which occur in response to chronic alcohol and subsequent withdrawal and abstinence. The changes that melatonin reverses have all been suggested to contribute to relapse. We have also demonstrated that melatonin decreases alcohol self-administration by selectively-bred alcohol-preferring rats. We are applying for renewal of the NIH grant that supported this work. Noradrenergic agents as therapy for alcohol abuse We are investigating mechanisms by which excessive CSF noradrenergic activation contributes to alcohol abuse and relapse after alcohol abstinence. Our current focus is on determining the best conditions for using the alpha-1 adrenergic receptor antagonist, prazosin, to decrease alcohol drinking, what subject characteristics determine response to prazosin, and what stages of the alcohol addiction process are most amenable to treatment with prazosin. This work is supported by a grant from NIH/NIAAA. Pharmacologic changes in noradrenergic regulation as a basis for alcohol therapy This is a unit in a P20 Developmental Center, supported by an NIH/NIAAA grant. The goal is to develop new treatments for alcoholism.