TY - JOUR

T1 - Central serotonin depletion affects rat brain areas differently: a qualitative and quantitative comparison between different treatment schemes

AU - Kornum, Birgitte Rahbek

AU - Licht, Cecilie Löe

AU - Weikop, Pia

AU - Knudsen, Gitte Moos

AU - Kleijn, Susana Aznar

PY - 2006/1/9

Y1 - 2006/1/9

N2 - Depletion of rat brain serotonin (5-hydroxytryptamin, 5-HT) has been widely used to study effects of serotonin and its interaction with other transmitter systems. Various treatment regimes for serotonin depletion have been applied, but the efficacy of these seems to vary considerably. So far, no studies have systematically examined and compared different approaches. The present work combines quantitative and qualitative measurements and compares six different treatment schemes for 5-HT depletion. Treatment outcome was evaluated by HPLC measurements of 5-HT and 5-HIAA concentrations, and by 5-HT and tyrosine hydroxylase immunocytochemistry. The schemes included repeated administration of fenfluramine (FEN) and/or p-chlorophenylalanine (pCPA). The most efficient treatment for rat brain 5-HT depletion was the combined treatment with one daily pCPA (200 mg/kg) injection for 3 days followed by one injection of d,l-FEN (20 mg/kg) on the fourth day, causing a 94.9% brain 5-HT depletion. Immunostaining revealed a distinct brain distribution of the remaining 5-HT, with an almost complete depletion of 5-HT in the cerebral cortex, hippocampus and thalamus, while a substantial amount of 5-HT still was left in the raphe nuclei, the medial forebrain bundle, and the medial eminence. FEN or pCPA treatment alone caused from 68.2 to 94.0% decrease in 5-HT levels. While the pattern of 5-HT depletion using pCPA alone was comparable to the one seen with the combined treatment, the 5-HT depletion using FEN alone showed a different pattern with 5-HT distributed in several brain regions.

AB - Depletion of rat brain serotonin (5-hydroxytryptamin, 5-HT) has been widely used to study effects of serotonin and its interaction with other transmitter systems. Various treatment regimes for serotonin depletion have been applied, but the efficacy of these seems to vary considerably. So far, no studies have systematically examined and compared different approaches. The present work combines quantitative and qualitative measurements and compares six different treatment schemes for 5-HT depletion. Treatment outcome was evaluated by HPLC measurements of 5-HT and 5-HIAA concentrations, and by 5-HT and tyrosine hydroxylase immunocytochemistry. The schemes included repeated administration of fenfluramine (FEN) and/or p-chlorophenylalanine (pCPA). The most efficient treatment for rat brain 5-HT depletion was the combined treatment with one daily pCPA (200 mg/kg) injection for 3 days followed by one injection of d,l-FEN (20 mg/kg) on the fourth day, causing a 94.9% brain 5-HT depletion. Immunostaining revealed a distinct brain distribution of the remaining 5-HT, with an almost complete depletion of 5-HT in the cerebral cortex, hippocampus and thalamus, while a substantial amount of 5-HT still was left in the raphe nuclei, the medial forebrain bundle, and the medial eminence. FEN or pCPA treatment alone caused from 68.2 to 94.0% decrease in 5-HT levels. While the pattern of 5-HT depletion using pCPA alone was comparable to the one seen with the combined treatment, the 5-HT depletion using FEN alone showed a different pattern with 5-HT distributed in several brain regions.

U2 - 10.1016/j.neulet.2005.09.013

DO - 10.1016/j.neulet.2005.09.013

M3 - Journal article

C2 - 16213658

VL - 392

SP - 129

EP - 134

JO - Neuroscience letters. Supplement

JF - Neuroscience letters. Supplement

SN - 0167-6253

IS - 1-2

ER -