Chronic morphine alters dopamine transporter density in the rat brain: possible role in the mechanism of drug addiction.
The effect of acute or chronic morphine treatment on dopamine transporters was studied with the selective transporter blocker [3H]GBR12935. Chronic, but not acute treatment of rats with morphine significantly decreased the Bmax of [3H]GBR12935 binding to membranes from the anterior basal forebrain, that includes the nucleus accumbens, but had no such effect on binding to striatum membranes. No effect on the affinity (Kd) of the radioligand to either one of the two brain regions was observed. The selectivity of morphine interaction with the dopamine system was tested with a ligand that binds selectively to serotonin transporters, [3H]citalopram. Neither acute nor chronic morphine altered [3H]citalopram binding to the anterior basal forebrain, or the striatum membranes. It is suggested, therefore, that chronic morphine treatment has a long-lasting and selective effect on the activity of dopamine transporters in the dopaminergic reward pathway, but not in the striatum.
Simantov
R
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Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015283:Citalopram / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000378:metabolism; D009928:Organ Specificity; D010879:Piperazines / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins; D014316:Tritium
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D015283:Citalopram; D014316:Tritium; D009020:Morphine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D004298:Dopamine