title: Individual differences in response to novelty predict prefrontal cortex dopamine transporter function and cell surface expression.
abstract: Previous research has shown that individual differences in response to novelty predict self-administration and the locomotor response to psychostimulant drugs of abuse. The aim of the present study was to determine if individual differences in response to novelty based on inescapable or free-choice novelty tests predict dopamine transporter (DAT) function and trafficking as well as nicotine-induced modulation of DAT. Results show that the maximal velocity (Vmax) of [3H]dopamine uptake into prefrontal cortex (PFC) synaptosomes correlated negatively with the locomotor response to inescapable novelty. In contrast, Vmax correlated positively with novelty place preference in the free-choice novelty test. The divergent correlations between DAT and the two behavioral phenotypes suggest a differential contribution of DAT in these phenotypes, which are known not to be isomorphic. Furthermore, rats categorized as high responders to inescapable novelty had lower Vmax values, which were accompanied by less DAT expression at the cell surface in PFC compared with low responders, suggesting that inherent individual differences in DAT cellular localization may underlie the differential response to novelty. Compared with the saline control, nicotine increased Vmax and cell surface DAT immunoreactivity in PFC from high responders but not from low responders. Similarly, nicotine increased Vmax and cell surface DAT in PFC in rats classified as low in novelty place preference but not in rats classified as high in novelty place preference. Thus, despite the different behavioral phenotypes, the pharmacological effect of nicotine to increase DAT function and cell surface expression was apparent, such that rats with inherently lower DAT function show a greater sensitivity to the neurochemical effect of nicotine.
authors.affiliation: College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536-0082, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bardo
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Bruntz
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Stairs
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000378:metabolism; D010641:Phenotype; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes; D014029:Tobacco Use Disorder / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011956:Receptors, Cell Surface; C054634:methyllycaconitine; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D009538:Nicotine; D003042:Cocaine; D004298:Dopamine; D000157:Aconitine