Letter from Eric J. Nestler to Marshall W. Nirenberg
Nestler shares findings from Yale University School of Medicine's work on neuroblastoma cells. They found that chronic
morphine treatment increases the levels of specific enzymes and proteins in the brain. Nestler sees this work as a support
and an extension of Nirenberg's novel proposal for a role for cyclic AMP in mediating opiate addiction in the 1970s.
Based on your earlier work on neuroblastoma cells, we have been studying the involvement of the cyclic AMP system in opiate
addiction in the rat locus coeruleus. Similar to your earlier findings, we have found that chronic morphine treatment increases
levels of certain G-proteins, adenylate cyclase activity, cyclic AMP-dependent protein kinase activity, and certain phosphoprotein
substrates for the protein kinase in this brain region. Interestingly, these effects were all specific to the locus coeruleus,
as they were not observed in the other brain regions examined. Enclosed please find reprints that describe some of our work
on opiate action in the locus coeruleus. I thought you might be interested in them, as they support and extend your novel
proposal of a role for the cyclic AMP system in mediating opiate addiction elaborated over ten years ago.
Eric J. Nestler, M.D., Ph.D.
Assistant Professor of Psychiatry and Pharmacology