ReviewNeurotoxicity research2015
DSP4, a selective neurotoxin for the locus coeruleus noradrenergic system. A review of its mode of action.
Review in Neurotoxicity research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 107 citations in OpenAlex.
- Renovating the Barnes maze for mouse models of dementia with STARR FIELD: A 4-day protocol for learning rate, retention, and cognitive flexibility.Methods (San Diego, Calif.) · 2026Article
- The role of the locus coeruleus in giant migrating contractions of colonic motility in Suncus murinus.Experimental brain research · 2026Article
- Synergetic effect of a DSP4-induced locus coeruleus lesion and systemic LPS exacerbates substantia nigra dopaminergic neuron loss.Scientific reports · 2025Article
- Astrocytic CaNature neuroscience · 2025Article
- A rat model of volitional mutual social interactions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Chronic voluntary exercise induces plasticity of noradrenaline-activated dopamine DMolecular brain · 2025Article
- Long-term exposure to excessive norepinephrine in the brain induces tau aggregation, neuronal death, and cognitive deficits in early tau transgenic mice.Aging cell · 2025Article
- The locus coeruleus, a blue spot for early diagnosis and prognosis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
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- LC-derived excitatory synaptic transmission to dorsal raphe serotonin neurons is inhibited by activation of alpha2-adrenergic receptors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis.Research square · 2024Article
- GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation.Scientific reports · 2024Article
- Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease.Handbook of experimental pharmacology · 2024Review
- The effects of locus coeruleus ablation on mouse brain volume and microstructure evaluated by high-field MRI.Frontiers in cellular neuroscience · 2024Article
- Norepinephrine regulates calcium signals and fate of oligodendrocyte precursor cells in the mouse cerebral cortex.Nature communications · 2023Article
- Norepinephrine depletion in the brain sex-dependently modulates aspects of spatial learning and memory in female and male rats.Psychopharmacology · 2023Article
- The locus coeruleus directs sensory-motor reflex amplitude across environmental contexts.Current biology : CB · 2023Article
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- Noradrenaline transporter PET reflects neurotoxin-induced noradrenaline level decrease in the rat hippocampus.EJNMMI research · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) is a selective neurotoxin for the locus coeruleus noradrenergic system in the rodent and bird brain. It readily passes the blood-brain barrier and cyclizes to a reactive aziridinium derivative that is accumulated into the noradrenergic nerve terminals via the noradrenaline transporter. DSP4 is also an irreversible inhibitor of this transporter. Within the nerve terminals the aziridinium derivative reacts with unknown vital cellular components, destroying the terminals. At the dose 50 mg/kg i.p. this is characterized by a rapid and long-lasting loss of noradrenaline and a slower decrease in the dopamine-β-hydroxylase enzyme activity and immunoreactivity in the regions innervated from locus coeruleus. The tissue level of noradrenaline is reduced to 10-30% of the normal value. The extraneuronal concentration is, on the other hand, increased due to inflow from non-lesioned regions. Like the peripheral sympathetic nerves the non-locus coeruleus noradrenergic systems in the rodent brain is resistant to the neurotoxic action of DSP4. Serotoninergic and dopaminergic nerves are only slightly or not at all affected by DSP4. The neurotoxic effect is counteracted by pretreatment with noradrenaline uptake inhibitors (e.g., desipramine). MAO-B inhibitors of the N-propargylamine type (e.g., selegiline) also counteract the DSP4-induced neurotoxicity with another, yet unknown mechanism. Because of its selectivity for the locus coeruleus system DSP4 is a useful tool in studies of the functional role of this noradrenergic system in the brain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.