Long-term food restriction down-regulates the density of serotonin transporters in the rat frontal cortex.
The influence of feeding rats only half the amount of their normal daily intake of a complete rat chow on the affinity and the density of serotonin (5-HT) transporters was measured in membrane preparations of the frontal cortex and the midbrain by a [3H]paroxetine binding assay. In young rats (10 weeks), a significant reduction of about 30% of the Bmax values of [3H]paroxetine binding occurred in the frontal cortex after 1 and 2 weeks of restricted food intake. No starvation-induced decline of the density of 5-HT transporters was seen in the midbrain. When older rats (50 weeks) were subjected to the same 50% reduction of daily food intake for 2 weeks, no such down-regulation of the density of cortical 5-HT transporters was observed. The affinity of the 5-HT transporters, as indicated by the unchanged Kd values of [3H]paroxetine binding, was not affected by semistarvation in both regions and at both ages. The observed decline of [3H]paroxetine binding sites in the frontal cortex of young adult rats is the first demonstration of long-term regulatory phenomena of brain 5-HT transporters triggered by a physiologic stimulus.
Huether
G
G
Department of Psychiatry, University of Göttingen, Germany.
Zhou
D
D
Schmidt
S
S
Wiltfang
J
J
Rüther
E
E
D000375:Aging / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis*; D015536:Down-Regulation / Q000502:physiology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D017374:Paroxetine / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics; D013217:Starvation / Q000378:metabolism*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493232:Slc6a4 protein, rat