Effects of 5,7-dihydroxytryptamine depletion of tissue serotonin levels onextracellular serotonin in the striatum assessed with in vivo microdialysis: Relationship to behavior

Effects of i.c.v. administration of 5,7-dihydroxytryptamine (5,7-DHT) on bi ochemistry and behavior were studied in awake Sprague-Dawley rats. It was f ound that 5,7-DHT depletion of striatal tissue levels of serotonin (5-HT) d oes not diminish extracellular levels until substantial depletions occur. T his finding is similar to those observed after 6-hydroxydopamine lesions of the brain dopamine systems. Although varying amounts of 5,7-DHT produced s erotonin depletions in striatal tissue, decreases in extracellular levels w ere only observed at tissue depletions greater than 60% compared to saline- injected control subjects. Thus, the effects of serotonin lesions which pro duce only moderate depletions may not be the result of decreased extracellu lar serotonin, but instead may be the result of compensatory changes in rem aining neurons which maintain normal extracellular serotonin concentrations . Different degrees of striatal serotonin depletion were associated with op posite behavioral effects. Moderate levels of serotonin depletion (50-75%) produced evidence of increased anxiety, while these effects were no longer seen in rats with more severe 5-HT depletions (>75%). Synapse 33:16-25, 199 9. (C) 1999 Wiley-Liss, Inc.