Download Does Drug Dependence Require Protein Synthesis

Does Drug Dependence Require Protein Synthesis?
Michael J Kuhar, Ph.D.
Much evidence that drug addiction requires protein synthesis in brain has been
accumulating over the years. Naturally, this is difficult to test in humans. However,
mathematical modeling allows us the opportunity to carry out a virtual experiment. The
approach utilized here is to examine the time course of onset of addiction and test if the
time course follows the same pattern or time course of protein synthesis. The equations
governing the time course of protein synthesis are well known.
In the first part, it will be shown that time courses of protein synthesis have the same
shape as that of the time course for onset of addiction. Moreover, the half lives
demanded by the model are in the range of the half lives of brain proteins. This modeling
approach has been applied to other drugs as well.
In the second part, a very detailed time course of the onset of dependence was generated
in rats. Not only did the time course of chronic dependence have the same properties as
the time course of protein synthesis, it was possible to identify a short term component
which seems to be acute dependence.
In summary, the time course of onset of drug dependence is indistinguishable from the
time course of protein synthesis, and the half lives required are reasonable and the same
as those in brain. A detailed analysis revealed that both acute and chronic dependence
can be resolved by the model, each having distinct properties.