Sodium dependent [3H]cocaine binding associated with dopamine uptake sites in the rat striatum and human putamen decrease after dopaminergic denervation and in Parkinsons disease

Naunyn Schmiedebergs Arch Pharmacol. 1985 May;329(3):227-35. doi: 10.1007/BF00501873.


The binding of radiolabelled cocaine, an inhibitor of dopamine uptake, to the post-mortem human putamen was studied and compared to that in the rat striatum. Saturation analysis of [3H]cocaine binding to the human putamen revealed the presence of a high affinity component of binding with a Kd of 0.21 mumol/l and a Bmax of 1.47 pmol/mg protein. In addition a low affinity component (Kd = 26.4 mumol/l) was demonstrated, having a Bmax of 42.2 pmol/mg protein. Also in the rat striatum [3H]cocaine binding was both of high affinity (Kd = 0.36 mumol/l, Bmax = 5.56 pmol/mg protein) and low affinity (Kd = 25.9 mumol/l, Bmax = 35.6 pmol/mg protein). A pharmacological characterisation of high affinity [3H]cocaine binding to rat striatal membranes clearly indicates an association with the neuronal dopamine transporter. The IC50 values of 8 selected drugs for inhibition of [3H]cocaine binding in the rat striatum were highly significantly correlated with their potency to inhibit [3H]dopamine uptake into slices of the rat striatum. [3H]Cocaine binding was stereospecifically inhibited by (+)nomifensine and (+)diclofensine which were 50-80-fold more active than their respective (-)isomers. Drugs with dopamine releasing activity were more potent at inhibiting [3H]dopamine uptake than at competing for the high affinity site of [3H]cocaine binding. A highly significant correlation was found between IC50 values for [3H]cocaine binding in the rat striatum and the human putamen. Further evidence in support of an association of [3H]cocaine binding in the rat striatum with the dopamine transporter was obtained from lesion studies. Thus, intranigral 6-hydroxydopamine administration produced a marked (67%) decrease in striatal [3H]cocaine binding.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Binding Sites
  • Biological Transport / drug effects
  • Cocaine / metabolism*
  • Cocaine / pharmacology
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Humans
  • Hydroxydopamines / pharmacology
  • In Vitro Techniques
  • Membrane Transport Proteins / metabolism
  • Oxidopamine
  • Parkinson Disease / metabolism*
  • Putamen / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Sodium / metabolism


  • Hydroxydopamines
  • Membrane Transport Proteins
  • Oxidopamine
  • Sodium
  • Cocaine
  • Dopamine