Lack of increase in dopamine transporter binding or function in rat brain tissue after treatment with blockers of neuronal uptake of dopamine

Neuropharmacology. 1991 Jan;30(1):89-92. doi: 10.1016/0028-3908(91)90047-f.

Abstract

Rats were pretreated daily for 10 days with a dopamine (DA) uptake blocker ([+]amphetamine, benztropine, cocaine, GBR-12909, mazindol, or nomifensine) or control vehicle and, after 1-4 days of no treatment, striatal tissue was fractionated to provide synaptosomes and membranes for assays of transport of 3H-DA or binding of 3H-GBR-12935. There were no significant increases of apparent maxima for uptake (Vmax) or binding (Bmax) or consistent changes in ligand affinity. Pharmacologic characterization of 3H-GBR-12935 binding extended the impression that this ligand has high affinity and selectivity for many agents which block neuronal uptake of DA uptake and much less for those which interact with DA receptors or other amine transporters. The results suggest that dopamine transporters are not regulated in the same way as receptors, nor influenced similarly toward upregulation and supersensitization by repeated treatment with antagonists.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benztropine / pharmacology*
  • Carrier Proteins / metabolism*
  • Cocaine / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine Antagonists
  • Dopamine Plasma Membrane Transport Proteins
  • Kinetics
  • Ligands
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nomifensine / pharmacology*
  • Piperazines / metabolism
  • Rats
  • Rats, Inbred Strains
  • Reference Values

Substances

  • Carrier Proteins
  • Dopamine Antagonists
  • Dopamine Plasma Membrane Transport Proteins
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Piperazines
  • Nomifensine
  • Benztropine
  • 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine
  • Cocaine
  • Dopamine