SEROTONIN TRANSPORTERS IN THE RAT FRONTAL-CORTEX - LACK OF CIRCADIAN RHYTHMICITY BUT DOWN-REGULATION BY FOOD RESTRICTION

Molecular biological findings have indicated that the affinity and the density of presynaptic serotonin transporters may be subject to adapt ive regulation, but the physiological conditions that may act to trigg er such changes are presently unknown. By means of [H-3]-paroxetine bi nding to rat cortical membranes, we studied the influence of two physi ological variables that are clearly associated with altered serotonerg ic activity-circadian rhythm and semistarvation-on K-D and B-max value s of the serotonin transporter of the rat frontal cortex. No circadian fluctuations of both parameters were observed, Also, semistarvation ( 50% reduction of normal voluntary food intake) for 2 days had no effec t on either K-m or B-max values of cortical [H-3] paroxetine binding. Food restriction for either 7 days or 2 weeks, however, resulted in a significant, similar to 30%, reduction of the density of cortical sero tonin transporters with unchanged transporter affinity. These findings indicate that long-term changes in the density of cortical serotonin transporters can be induced by long-lasting alterations of certain env ironmental variables. Because the duration and the radius of action of presynaptically released serotonin are governed by the efficiency of the reuptake mechanism, such adaptive changes of serotonin transporter density must be expected to cause long-term alterations of the modula tory impact of the central serotonin system on certain brain functions .