PMID- 10899292
OWN - NLM
STAT- MEDLINE
DCOM- 20001004
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 871
IP  - 2
DP  - 2000 Jul 21
TI  - Recovery from methamphetamine induced long-term nigrostriatal dopaminergic 
      deficits without substantia nigra cell loss.
PG  - 259-70
AB  - After administration of methamphetamine (METH) (2x2 mg/kg, 6 h apart) to vervet 
      monkeys, long term but reversible dopaminergic deficits were observed in both in 
      vivo and post-mortem studies. Longitudinal studies using positron emission 
      tomography (PET) with the dopamine transporter (DAT)-binding ligand, [11C]WIN 
      35,428 (WIN), were used to show decreases in striatal WIN binding of 80% at 1 
      week and only 10% at 1.5 years. A post-mortem characterization of other METH 
      subjects at 1 month showed extensive decreases in immunoreactivity (IR) profiles 
      of tyrosine hydroxylase (TH), DAT and vesicular monoamine transporter-2 (VMAT) in 
      the striatum, medial forebrain bundle and the ventral midbrain dopamine (VMD) 
      cell region. These IR deficits were not associated with a loss of VMD cell number 
      when assessed at 1.5 years by stereological methods. Further, at 1.5 years, IR 
      profiles of METH subjects throughout the nigrostriatal dopamine system appeared 
      similar to controls although some regional deficits persisted. Collectively, the 
      magnitude and extent of the dopaminergic deficits, and the subsequent recovery 
      were not suggestive of extensive axonal degeneration followed by regeneration. 
      Alternatively, this apparent reversibility of the METH-induced neuroadaptations 
      may be related primarily to long-term decreases in expression of VMD-related 
      proteins that recover over time.
FAU - Harvey, D C
AU  - Harvey DC
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los 
      Angeles, CA 90095-1735, USA.
FAU - Lacan, G
AU  - Lacan G
FAU - Tanious, S P
AU  - Tanious SP
FAU - Melega, W P
AU  - Melega WP
LA  - eng
GR  - NIDA-DA11237/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Carrier Proteins)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Vesicular Biogenic Amine Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 44RAL3456C (Methamphetamine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
SB  - IM
MH  - Animals
MH  - Carbon Radioisotopes
MH  - Carrier Proteins/drug effects/metabolism
MH  - Cell Count
MH  - Cercopithecus
MH  - Dopamine Plasma Membrane Transport Proteins
MH  - Male
MH  - Membrane Glycoproteins/drug effects/metabolism
MH  - *Membrane Transport Proteins
MH  - Methamphetamine/*adverse effects
MH  - Neostriatum/*drug effects/metabolism/pathology
MH  - Nerve Degeneration/*chemically induced/pathology/physiopathology
MH  - *Nerve Tissue Proteins
MH  - Neural Pathways/*drug effects/metabolism/pathology
MH  - *Neuropeptides
MH  - Recovery of Function/*drug effects/physiology
MH  - Substantia Nigra/*drug effects/metabolism/pathology
MH  - Time Factors
MH  - Tomography, Emission-Computed
MH  - Tyrosine 3-Monooxygenase/drug effects/metabolism
MH  - Vesicular Biogenic Amine Transport Proteins
MH  - Vesicular Monoamine Transport Proteins
EDAT- 2000/07/19 11:00
MHDA- 2000/10/07 11:01
CRDT- 2000/07/19 11:00
PHST- 2000/07/19 11:00 [pubmed]
PHST- 2000/10/07 11:01 [medline]
PHST- 2000/07/19 11:00 [entrez]
AID - S0006-8993(00)02439-2 [pii]
AID - 10.1016/s0006-8993(00)02439-2 [doi]
PST - ppublish
SO  - Brain Res. 2000 Jul 21;871(2):259-70. doi: 10.1016/s0006-8993(00)02439-2.