title: Chronic blockade of opioid receptors alters the binding of [3H]GBR 12935 to dopamine transporter in rat brain regions and spinal cord.
abstract: The effect of chronic administration of naltrexone, an opioid receptor antagonist, on the activity of the dopamine transporter in brain regions and spinal cord was determined. Male Sprague-Dawley rats were implanted with a pellet containing 10 mg naltrexone for 7 days. Rats serving as controls were implanted with a placebo pellet. Two groups of rats were used. In one, the pellets were left intact, and in the other they were removed 16 h prior to sacrificing. The dopamine transporter was labeled with [3H]GBR 12935. The binding of [3H]GBR 12935 in rats in which naltrexone pellets were left intact was decreased by 63 and 31% in corpus striatum and spinal cord, respectively, when compared to placebo pellet implanted controls. The decrease in binding in the striatum was due to changes in the Bmax value of [3H]GBR 12935; the Kd values did not differ. In hypothalamus, pons-medulla, hippocampus, midbrain, cortex, and amygdala of naltrexone and placebo pellet implanted rats, the binding of [3H]GBR 12935 did not differ. In naltrexone-treated rats from which pellets had been removed, the binding of [3H]GBR 12935 was decreased in hippocampus, amygdala, and spinal cord by 68, 77, and 61%, respectively, in comparison with tissues from the control rats. The results indicate that chronic blockade of opioid receptors results in downregulation of dopamine transporter in selected brain regions and spinal cord.
authors.affiliation: Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago 60612, USA.
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
authors.forename: K P
authors.initials: KP
authors.lastname: Gudehithlu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; D010879:Piperazines; D014316:Tritium; D009271:Naltrexone; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine