Withdrawal of repeated cocaine decreases autoradiographic [3H]mazindol-labelling of dopamine transporter in rat nucleus accumbens

Eur J Pharmacol. 1991 Oct 2;203(1):141-4. doi: 10.1016/0014-2999(91)90804-y.

Abstract

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.

MeSH terms

  • Animals
  • Autoradiography
  • Carrier Proteins / metabolism*
  • Cocaine / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Densitometry
  • Desipramine / pharmacology
  • Dopamine Plasma Membrane Transport Proteins
  • Down-Regulation / drug effects
  • Male
  • Mazindol / metabolism*
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Nucleus Accumbens / anatomy & histology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Rats
  • Substance Withdrawal Syndrome / metabolism*

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Mazindol
  • Cocaine
  • Desipramine