Chronic blockade of opioid receptors alters the binding of [3H]GBR 12935 to dopamine transporter in rat brain regions and spinal cord.
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.
Bhargava
H N
HN
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago 60612, USA.
Gudehithlu
K P
KP
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
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