Enhanced dopamine uptake in the striatum following repeated restraint stress.
In mice administered chronic stress--repeated overnight restraint stress for 7 days--there was a prolonged enhancement of dopamine (DA) uptake into synaptosomes. The mRNA for the DA transporter (DAT) was found to be concomitantly increased in the midbrain, as was the binding of the transporter ligand mazindol to DAT in the nucleus accumbens and caudate-putamen. Kinetic analysis showed an increase in Vmax for DA, with little change in Km. No changes in tyrosine hydroxylase activity and tissue DA or 3,4-dihydroxyphenylacetic acid (DOPAC) content were observed. However, homovanillic acid (HVA) was found to be increased in the striatum of the stressed animals. Enhanced DAT activity attributable to chronic stress was still observed in animals treated with the DA D2 receptor antagonist haloperidol or the glucocorticoid receptor antagonist mifepristone. Modulation of DAT activity may be a physiological mechanism for regulating the concentration of DA that reaches receptors, following periods of stress.
Copeland
Benjamin J
BJ
The Neuroscience Program, Division of Molecular Neuropsychopharmacology, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA.
Neff
Norton H
NH
Hadjiconstantinou
Maria
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000315:Adrenalectomy / Q000379:methods; D000818:Animals; D001522:Behavior, Animal; D001679:Biogenic Amines / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics; D004563:Electrochemistry / Q000379:methods; D006220:Haloperidol / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008454:Mazindol / Q000493:pharmacokinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012149:Restraint, Physical / Q000379:methods*; D013312:Stress, Physiological / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D014443:Tyrosine / Q000493:pharmacokinetics
D001679:Biogenic Amines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D006727:Hormone Antagonists; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493215:Slc6a3 protein, mouse; C503848:homovanillamine; D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D015735:Mifepristone; D014443:Tyrosine; D008454:Mazindol; D006220:Haloperidol; D004298:Dopamine; D003345:Corticosterone