Rat strain differences in peripheral and central serotonin transporter protein expression and function.
Female Fischer 344 (F344) rats have been shown to display increased serotonin transporter (5-HTT) gene expression in the dorsal raphe, compared to female Lewis (LEW) rats. Herein, we explored, by means of synaptosomal preparations and in vivo microdialysis, whether central, but also peripheral, 5-HTT protein expression/function differ between strains. Midbrain and hippocampal [3H]paroxetine binding at the 5-HTT and hippocampal [3H]serotonin (5-HT) reuptake were increased in male and female F344 rats, compared to their LEW counterparts, these strain differences being observed both in rats of commercial origin and in homebred rats. Moreover, in homebred rats, it was found that these strain differences extended to blood platelet 5-HTT protein expression and function. Saturation studies of midbrain and hippocampal [3H]paroxetine binding at the 5-HTT, and hippocampal and blood platelet [3H]5-HT reuptake, also revealed significant strain differences in Bmax and Vmax values. Although F344 and LEW rats differ in the activity of the hypothalamo-pituitary-adrenal (HPA) axis, manipulations of that axis revealed that the strain differences in hippocampal [3H]paroxetine binding at 5-HTTs and [3H]5-HT reuptake were not accounted for by corticosteroids. Hippocampal extracellular 5-HT levels were reduced in F344 rats, compared to LEW rats, with the relative, but not the absolute, increase in extracellular 5-HT elicited by the local administration of citalopram being larger in F344 rats. Because the aforementioned strain differences did not lie in the coding sequences of the 5-HTT gene, our results open the promising hypothesis that F344 and LEW strains model functional polymorphisms in the promoter region of the human 5-HTT gene.
Fernandez
Francesca
F
NeuroGénétique et Stress, INSERM U471-INRA UR502, Institut F. Magendie, Rue Camille Saint Saëns, 33077 Bordeaux Cédex, France.
Sarre
Sophie
S
Launay
Jean-Marie
JM
Aguerre
Sylvie
S
Guyonnet-Dupérat
Véronique
V
Moisan
Marie-Pierre
MP
Ebinger
Guy
G
Michotte
Yvette
Y
Mormède
Pierre
P
Chaouloff
Francis
F
D000315:Adrenalectomy; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D015342:DNA Probes; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology*; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000378:metabolism; D017551:Microdialysis; D009419:Nerve Tissue Proteins; D017933:Peripheral Nervous System / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013045:Species Specificity
D002352:Carrier Proteins; D015283:Citalopram; D003345:Corticosterone; D015342:DNA Probes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493232:Slc6a4 protein, rat