Withdrawal of repeated cocaine decreases autoradiographic [3H]mazindol-labelling of dopamine transporter in rat nucleus accumbens.
The in vitro autoradiographic distribution of desipramine-insensitive specific [3H]mazindol binding sites (labelling the dopamine transporter) was determined in brain sections from rats receiving repeated i.v. infusions of saline or cocaine (1 mg/kg, every 12 min for 2 h/day), for 10 days. Brains were removed either within 15 min of or 10 days after the last treatment. A marked dorsal-to-ventral gradient in [3H]mazindol binding appeared in the striatum with the dorsal caudate putamen showing the greatest binding and the medial shell of the nucleus accumbens the least. Cocaine-associated changes in [3H]mazindol-labelled dopamine uptake sites occurred only in the nucleus accumbens (57 and 66% decrease in the lateral core and medial shell, respectively), of animals 10 days after the last treatment. Down-regulation of the dopamine transporter in the nucleus accumbens by withdrawal of chronic cocaine may be one of the mechanisms involved in cocaine's long-term abstinence effects.
Sharpe
L G
LG
NIDA Addiction Research Center, Baltimore, MD 21224.
Pilotte
N S
NS
Mitchell
W M
WM
De Souza
E B
EB
D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003720:Densitometry; D003891:Desipramine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D008454:Mazindol / Q000378:metabolism*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D008454:Mazindol; D003042:Cocaine; D003891:Desipramine