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Monoaminergic Changes in Locus Coeruleus and Dorsal Raphe Nucleus Following Noradrenaline Depletion

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Abstract

The goal of our study was to assess the monoaminergic changes in locus coeruleus (LC) and dorsal raphe nucleus (DRN) following noradrenaline (NA) depletion. Seven days after a single N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) intraperitoneal administration in mice, we observed a decrease of NA in both the LC and DRN, as well as in prefrontal cortex (PFC) and hippocampus (HIPP). Moreover, an increase of serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) was detected at LC level, while no change was found in DRN. DSP-4 also caused a significant decrease of dopamine (DA) tissue content in HIPP and DRN, without affecting the LC and the PFC. A decrease of DA metabolite, homovanillic acid (HVA), was found in the DRN of NA-depleted mice. These results highlight that the neurotoxic action of DSP-4 is not restricted to LC terminal projections but also involves NA depletion at the cell body level, where it is paralleled by adaptive changes in both serotonergic and dopaminergic systems.

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Acknowledgments

The authors thank Dr Antonio Petrella at the Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata for his invaluable veterinary assistance.

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Correspondence to Tommaso Cassano.

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T. Cassano and S. Gaetani have contributed equally to the present study.

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Cassano, T., Gaetani, S., Morgese, M.G. et al. Monoaminergic Changes in Locus Coeruleus and Dorsal Raphe Nucleus Following Noradrenaline Depletion. Neurochem Res 34, 1417–1426 (2009). https://doi.org/10.1007/s11064-009-9928-5

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