Depletion and repletion of cortical tissue and dialysate 5-HT after reserpine

Reserpine (5 mg/kg s.c.) was given to rats kept under a reversed light-dark cycle and 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) determined in frontal cortex tissue and dialysate at various times after drug treatment. The decline and return of spontaneous locomotor activity was also measured. Tissue 5-HT was depleted to 16% of control values 24 hr after drug administration and had recovered to 61% of control after 21 days. Locomotion was profoundly reduced by 7 hr after reserpine but had returned to normal at 4 days. Dialysate 5-HT, both basal and its rise on potassium (K+) stimulation, was reduced at 1, 7 and 21 days after reserpine but the K+ stimulated increases (as % of control) did not rise above % tissue repletion, thus providing evidence against increased mobilization of the transmitter from the partially repleted vesicular stores. However, at 1 day after reserpine, basal dialysate 5-HT was proportionately less reduced than tissue 5-HT suggesting that release from a reserpine insensitive (extravesicular) pool was more effective than from the vesicular pool. At this time, the K(+)-stimulated rise of dialysate 5-HT was proportionately more reduced than tissue 5-HT. By 21 days, values converged so that % changes of the 3 compartments were the same suggesting that at this time both basal and K+ stimulated dialysate 5-HT was essentially all derived from the vesicular pool.