Antidepressant drug induced alterations in binding to central dopamine transporter sites in the Wistar Kyoto rat strain.
The Wistar Kyoto (WKY) rat has been proposed as an animal model of depressive behavior. Exposing WKY rats to stress stimulation produces symptoms such as anhedonia, psychomotor retardation, ambivalence and negative memory bias. Given the role of the mesolimbic dopamine (DA) system in cognitive, emotional and motivational behaviors, we previously examined the distribution of DA transporter (DAT) sites in the brains of WKY compared to Wistar (WIS) and Sprague-Dawley (S-D) rats. WKY rats exhibited significant differences in DAT binding sites in the cell body as well as mesolimbic areas compared to the other strains. It was reasoned that these differences may lead to altered synaptic levels of DA in specific brain regions thus contributing to the behavioral differences observed in this rat strain. Thus, the present study examined whether repeated treatment with antidepressant drugs that block the uptake of DA (nomifensine and bupropion) would modify [3H]-GBR12935 binding to DAT sites in WKY rats compared to WIS and S-D rats. The results indicate that while nomifensine and bupropion increased the binding of [3H]-GBR12935 to DAT sites in the mesocorticolimbic regions in WKY rats, these drugs increased the binding of [3H]-GBR12935 to DAT sites in the cell body areas in WIS rats but not in S-D and WKY rats. The data from this study suggest that antidepressant induced alterations in DAT sites in the mesocorticolimbic brain regions may play a role in the behavioral improvement seen in WKY rats, as measured by the Open Field Test (OFT) and the Porsolt Forced Swim Test (FST).
Jiao
Xilu
X
University of the Sciences in Philadelphia, Department of Pharmacology and Toxicology (Box 118), 600 South 43rd Street, Philadelphia, PA 19104, USA.
Paré
William P
WP
Tejani-Butt
Shanaz M
SM
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004347:Drug Interactions; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011921:Rats, Inbred WKY / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013045:Species Specificity; D014316:Tritium / Q000493:pharmacokinetics
D000928:Antidepressive Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D010879:Piperazines; D014316:Tritium; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine