WITHDRAWAL OF REPEATED COCAINE DECREASES AUTORADIOGRAPHIC [H-3] MAZINDOL-LABELING OF DOPAMINE TRANSPORTER IN RAT NUCLEUS-ACCUMBENS

The in vitro autoradiographic distribution of desipramine-insensitive specific [H-3]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 [H-3]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 [H-3]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.