PMID- 19038779
OWN - NLM
STAT- MEDLINE
DCOM- 20090324
LR  - 20220223
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 328
IP  - 3
DP  - 2009 Mar
TI  - Cocaine alters vesicular dopamine sequestration and potassium-stimulated dopamine 
      release: the role of D2 receptor activation.
PG  - 807-12
LID - 10.1124/jpet.108.146159 [doi]
AB  - Cocaine is a psychostimulant that inhibits the inward transport of dopamine (DA) 
      via the neuronal DA transporter, thereby increasing DA concentrations in the 
      synaptic cleft. Cocaine administration also causes a redistribution of striatal 
      vesicular monoamine transporter (VMAT)-2-containing vesicles that co-fractionate 
      with synaptosomal membranes after osmotic lysis (referred to herein as 
      membrane-associated vesicles) to a nonmembrane-associated, cytoplasmic 
      subcellular fraction. Although previous studies from our laboratory have focused 
      on the impact of cocaine on cytoplasmic vesicles, the present report describes 
      the pharmacological effects of cocaine on the membrane-associated vesicle 
      population. Results revealed that the redistribution of VMAT-2 and associated 
      vesicles away from synaptosomal membranes is associated with a decrease in total 
      DA transport and DA content in the membrane-associated VMAT-2-containing 
      subcellular fraction. Cocaine also decreases the velocity and magnitude of 
      K+-stimulated exocytotic DA release from whole striatal suspensions. The 
      cocaine-induced VMAT-2 redistribution, decrease in DA release, and decrease in 
      total DA transport are mediated by D2 receptors as these events were prevented by 
      pretreatment with the D2 receptor antagonist, eticlopride 
      [S-(-)-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxybenzamide 
      hydrochloride]. These data suggest that after cocaine administration, D2 
      receptors are activated because of increased synaptic DA, resulting in a 
      redistribution of DA-containing vesicles away from synaptosomal membranes, thus 
      leading to less DA released after a depolarizing stimulus. These findings provide 
      insight into not only the mechanism of action of cocaine but also mechanisms 
      underlying the regulation of dopaminergic neurons.
FAU - Farnsworth, Sarah J
AU  - Farnsworth SJ
AD  - Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 
      84112, USA.
FAU - Volz, Trent J
AU  - Volz TJ
FAU - Hanson, Glen R
AU  - Hanson GR
FAU - Fleckenstein, Annette E
AU  - Fleckenstein AE
LA  - eng
GR  - R01 DA004222-22/DA/NIDA NIH HHS/United States
GR  - R01 DA004222/DA/NIDA NIH HHS/United States
GR  - K05 DA000378/DA/NIDA NIH HHS/United States
GR  - DA00869/DA/NIDA NIH HHS/United States
GR  - P01 DA013367/DA/NIDA NIH HHS/United States
GR  - DA13367/DA/NIDA NIH HHS/United States
GR  - K05 DA000378-07/DA/NIDA NIH HHS/United States
GR  - DA11389/DA/NIDA NIH HHS/United States
GR  - DA019447/DA/NIDA NIH HHS/United States
GR  - K05 DA000378-08/DA/NIDA NIH HHS/United States
GR  - R01 DA011389/DA/NIDA NIH HHS/United States
GR  - DA04222/DA/NIDA NIH HHS/United States
GR  - P01 DA013367-05/DA/NIDA NIH HHS/United States
GR  - DA00378/DA/NIDA NIH HHS/United States
GR  - R01 DA004222-21/DA/NIDA NIH HHS/United States
GR  - P01 DA013367-06A2/DA/NIDA NIH HHS/United States
GR  - K02 DA019447/DA/NIDA NIH HHS/United States
GR  - R01 DA000869/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081126
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Slc18a2 protein, rat)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - I5Y540LHVR (Cocaine)
RN  - RWP5GA015D (Potassium)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cell Membrane/drug effects/physiology
MH  - Cocaine/*pharmacology
MH  - Corpus Striatum/drug effects/physiology
MH  - Dopamine/*metabolism
MH  - Electric Stimulation
MH  - Male
MH  - Potassium/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D2/drug effects/*physiology
MH  - Synaptic Vesicles/drug effects/physiology
MH  - Vesicular Monoamine Transport Proteins/drug effects/*physiology
PMC - PMC2682259
EDAT- 2008/11/29 09:00
MHDA- 2009/03/25 09:00
PMCR- 2010/03/01
CRDT- 2008/11/29 09:00
PHST- 2008/11/29 09:00 [pubmed]
PHST- 2009/03/25 09:00 [medline]
PHST- 2008/11/29 09:00 [entrez]
PHST- 2010/03/01 00:00 [pmc-release]
AID - jpet.108.146159 [pii]
AID - 0807 [pii]
AID - 10.1124/jpet.108.146159 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2009 Mar;328(3):807-12. doi: 10.1124/jpet.108.146159. Epub 
      2008 Nov 26.