Fast uptake and long-lasting binding of methamphetamine in the human brain: comparison with cocaine.
Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine's uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine's brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine's fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.
Fowler
Joanna S
JS
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. fowler@bnl.gov
Volkow
Nora D
ND
Logan
Jean
J
Alexoff
David
D
Telang
Frank
F
Wang
Gene-Jack
GJ
Wong
Christopher
C
Ma
Yeming
Y
Kriplani
Aarti
A
Pradhan
Kith
K
Schlyer
David
D
Jayne
Millard
M
Hubbard
Barbara
B
Carter
Pauline
P
Warner
Donald
D
King
Payton
P
Shea
Colleen
C
Xu
Youwen
Y
Muench
Lisa
L
Apelskog
Karen
K
D000328:Adult; D001741:Black or African American; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008694:Methamphetamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution; D044465:White People; D055815:Young Adult
D002250:Carbon Radioisotopes; D008694:Methamphetamine; D003042:Cocaine