Positron Emission Tomography Studies of Dopamine‐Enhancing Drugs

Although PET is technologically complex because the restricted time scale requires that radioisotope production, radiotracer synthesis, and PET imaging be carried out in the same place, the payoff is that compounds labeled with these isotopes can be used to track the distribution and movement of drugs in the brain and also measure drug effects on specific molecular targets in the human brain. Provided that appropriate radiotracers are available, one can determine the amount of a drug that gets into the brain, the minimum effective dose, the duration of action, or the binding site occupancy required to elicit a particular therapeutic or behavioral effect with a relatively small number of PET studies. Because studies are carried out directly in humans, the relationship of these parameters to behavior and to therapeutic efficacy can be evaluated. The possibilities are enormous and are largely driven by advances in PET technology (including radiotracer chemistry and instrumentation) that synergize with advances in neuropharmacology.

[1]  John G. Cull,et al.  REWARD DEFICIENCY SYNDROME , 1996 .

[2]  N. Volkow,et al.  Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers , 1993, Synapse.

[3]  G. Di Chiara,et al.  Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[4]  N. Volkow,et al.  Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging , 1998, Annals of neurology.

[5]  J S Fowler,et al.  Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain. , 1995, Archives of general psychiatry.

[6]  N. Volkow,et al.  Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson's disease , 1993, Neurology.

[7]  J S Fowler,et al.  Decreases in dopamine receptors but not in dopamine transporters in alcoholics. , 1996, Alcoholism, clinical and experimental research.

[8]  S. J. Gatley,et al.  Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects , 1997, Nature.

[9]  R Kieburtz,et al.  Effect of lazabemide on the progression of disability in early Parkinson's disease , 1996, Annals of neurology.

[10]  N. Volkow,et al.  Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. , 1998, The American journal of psychiatry.

[11]  Simon R. Cherry,et al.  The Changing Design of Positron Imaging Systems. , 1998, Clinical positron imaging : official journal of the Institute for Clinical P.E.T.

[12]  A. Wolf,et al.  Working Against Time: Rapid Radiotracer Synthesis and Imaging the Human Brain , 1997 .

[13]  N. Volkow,et al.  Brain monoamine oxidase A inhibition in cigarette smokers. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  N. Volkow,et al.  Inhibition of monoamine oxidase B in the brains of smokers , 1996, Nature.

[15]  N. Volkow,et al.  Slow recovery of human brain MAO B after L‐Deprenyl (Selegeline) withdrawal , 1994, Synapse.

[16]  N. Volkow,et al.  A novel strategy for the treatment of cocaine addiction , 1998, Synapse.

[17]  N. Volkow,et al.  Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. , 1998, The American journal of psychiatry.

[18]  M. Kuhar,et al.  Cocaine receptors on dopamine transporters are related to self-administration of cocaine. , 1987, Science.