Striatal dopamine nerve terminal markers in human, chronic methamphetamine users.
Methamphetamine is a drug that is significantly abused worldwide, Although long-lasting depletion of dopamine and other dopamine nerve terminal markers has been reported in striatum of nonhuman primates receiving very high doses of the psychostimulant, no information is available for humans. We found reduced levels of three dopamine nerve terminal markers (dopamine, tyrosine hydroxylase and the dopamine transporter) in post-mortem striatum (nucleus accumbens, caudate, putamen) of chronic methamphetamine users. However, levels of DOPA decarboxylase and the vesicular monoamine transporter, known to be reduced in Parkinson's disease, were normal. This suggests that chronic exposure to methamphetamine does not cause permanent degeneration of striatal dopamine nerve terminals at the doses used by the young subjects in our study. However, the dopamine reduction might explain some of the dysphoric effects of the drug, whereas the decreased dopamine transporter could provide the basis for dose escalation occurring in some methamphetamine users.
Wilson
J M
JM
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Kalasinsky
K S
KS
Levey
A I
AI
Bergeron
C
C
Reiber
G
G
Anthony
R M
RM
Schmunk
G A
GA
Shannak
K
K
Haycock
J W
JW
Kish
S J
SJ
D000328:Adult; D001344:Autopsy; D002352:Carrier Proteins / Q000737:chemistry; D002908:Chronic Disease; D003342:Corpus Striatum / Q000737:chemistry* / Q000187:drug effects*; D004296:Dopa Decarboxylase / Q000737:chemistry; D004298:Dopamine / Q000737:chemistry*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry; D026901:Membrane Transport Proteins; D008694:Methamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009714:Nucleus Accumbens / Q000737:chemistry; D011699:Putamen / Q000737:chemistry; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D002352:Carrier Proteins; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D004296:Dopa Decarboxylase; D004298:Dopamine