title: Environmental enrichment enhances sensitization to GBR 12935-induced activity and decreases dopamine transporter function in the medial prefrontal cortex.
abstract: Rats raised in an enriched condition (EC) during development display increased hyperactivity to the effect of acute amphetamine compared to rats raised in an impoverished condition (IC). The present study determined whether environmental enrichment differentially alters the effects of GBR 12935 administration, a selective dopamine transporter (DAT) inhibitor. Acutely, EC rats showed a greater, dose-dependent GBR 12935-induced increase in activity compared to IC rats; however, basal activity for EC rats was lower than for IC rats. After repeated GBR 12935, only EC rats exhibited behavioral sensitization. Kinetic analysis of DAT function in medial prefrontal cortex (mPFC) revealed that the maximal velocity of [3H]dopamine ([3H]DA) uptake in EC rats was less than in IC rats (4.9 +/- 0.6 and 7.7 +/- 0.6 pmol/min/mg, respectively), but not in striatum or nucleus accumbens. Furthermore, GBR 12935-induced inhibition of DAT function, [3H]GBR 12935 binding density and DA content in mPFC, striatum and nucleus accumbens were not different between EC and IC rats. However, dihydroxyphenylacetic acid content in mPFC was lower in EC than IC rats, whereas no differences were found in striatum and nucleus accumbens. These results suggest that EC-induced changes in activity may be due to decreased DAT function and decreased DA metabolism in the mPFC.
authors.affiliation: College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Thomas
authors.initials: T
authors.lastname: Green
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bardo
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004777:Environment; D006948:Hyperkinesis / Q000139:chemically induced; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000378:metabolism; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014316:Tritium / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; C493216:Slc6a3 protein, rat; D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D004298:Dopamine