PMID- 17651730
OWN - NLM
STAT- MEDLINE
DCOM- 20080313
LR  - 20220729
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 573
IP  - 1-3
DP  - 2007 Nov 14
TI  - Deprenyl treatment attenuates long-term pre- and post-synaptic changes evoked by 
      chronic methamphetamine.
PG  - 100-10
AB  - Deprenyl, used clinically in Parkinson's disease, has multiple pharmacological 
      effects which make it a good candidate to treat neurotoxicity. Thus, we 
      investigated deprenyl's ability to attenuate methamphetamine-induced dopamine 
      neurotoxicity. We also examined deprenyl's effect in changing markers associated 
      with psychostimulant sensitization. A potential therapeutic effect on either 
      pathological domain would be a boon in developing novel treatments for 
      methamphetamine abuse. Adult male Sprague-Dawley rats were split into 6 groups. 
      Three groups received a 7-day saline minipump with saline, 0.05 or 0.25 mg/kg SC 
      deprenyl injections given for 10 days before, during and 5 days after the 7-day 
      saline minipump implant. Similarly, 3 groups received methamphetamine pumps (25 
      mg/kg/day) with escalating daily injections of methamphetamine (0-6 mg/kg) in 
      addition to the minipump treatment. These rats also received saline, 0.05 or 0.25 
      mg/kg deprenyl injections given before, during and the 7-day minipump treatment. 
      Rats were killed on day 28 of withdrawal and brain samples taken. HPLC analysis 
      for dopamine and 3,4-Dihydroxy-Phenylacetic Acid (DOPAC) revealed a loss of 
      dopamine in the caudate and accumbens which was partially reversed by high dose 
      deprenyl. Tyrosine hydroxylase immunostaining in the midbrain was unaffected by 
      methamphetamine, suggesting that dopamine neurotoxicity was localized to the 
      caudate. Western blot analysis of the caudate after methamphetamine revealed 
      little change in Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid (AMPA) 
      GluR1 or N-Methyl-d-Aspartate (NMDA) NR2B subunits, or their phosphorylation 
      state. However, methamphetamine increased levels of GluR1 and its phosphorylation 
      state in the prefrontal cortex (PFC), and these increases were attenuated by 
      deprenyl. Methamphetamine also increased levels of PFC NR2B subunit, but these 
      increases were not attenuated by deprenyl. We suggest that deprenyl may be 
      effective in reducing the neurotoxic effects of methamphetamine and may also 
      attenuate changes in prefrontal AMPA receptor function, presumably more 
      associated with addiction rather than neurotoxicity.
FAU - Davidson, Colin
AU  - Davidson C
AD  - Department of Psychiatry and Behavioral Sciences, Box 3870, Duke University 
      Medical Center, Durham, NC 27710, USA. colda@duke.edu
FAU - Chen, Qiang
AU  - Chen Q
FAU - Zhang, Xiuwn
AU  - Zhang X
FAU - Xiong, Xueying
AU  - Xiong X
FAU - Lazarus, Cindy
AU  - Lazarus C
FAU - Lee, Tong H
AU  - Lee TH
FAU - Ellinwood, Everett H
AU  - Ellinwood EH
LA  - eng
GR  - R01 DA012768/DA/NIDA NIH HHS/United States
GR  - DA 10327/DA/NIDA NIH HHS/United States
GR  - DA 14323/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070704
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Receptors, AMPA)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 2K1V7GP655 (Selegiline)
RN  - 44RAL3456C (Methamphetamine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/analysis/metabolism
MH  - Animals
MH  - Antiparkinson Agents/administration & dosage/pharmacology
MH  - Blotting, Western
MH  - Body Weight/drug effects
MH  - Caudate Nucleus/drug effects/metabolism/pathology
MH  - Chromatography, High Pressure Liquid
MH  - Dopamine/analysis/metabolism
MH  - Dopamine Uptake Inhibitors/administration & dosage/toxicity
MH  - Dose-Response Relationship, Drug
MH  - Immunochemistry
MH  - Infusion Pumps, Implantable
MH  - Injections, Subcutaneous
MH  - Male
MH  - Mesencephalon/drug effects/metabolism/pathology
MH  - Methamphetamine/administration & dosage/*toxicity
MH  - Phosphorylation/drug effects
MH  - Prefrontal Cortex/drug effects/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/metabolism
MH  - Selegiline/administration & dosage/*pharmacology
MH  - Substantia Nigra/drug effects/metabolism/pathology
MH  - Synapses/*drug effects/physiology
MH  - Time Factors
MH  - Tyrosine 3-Monooxygenase/analysis/metabolism
EDAT- 2007/07/27 09:00
MHDA- 2008/03/14 09:00
CRDT- 2007/07/27 09:00
PHST- 2006/10/05 00:00 [received]
PHST- 2007/06/13 00:00 [revised]
PHST- 2007/06/21 00:00 [accepted]
PHST- 2007/07/27 09:00 [pubmed]
PHST- 2008/03/14 09:00 [medline]
PHST- 2007/07/27 09:00 [entrez]
AID - S0014-2999(07)00762-5 [pii]
AID - 10.1016/j.ejphar.2007.06.046 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2007 Nov 14;573(1-3):100-10. doi: 10.1016/j.ejphar.2007.06.046. 
      Epub 2007 Jul 4.