DSP-4: A novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats

Jaim-Etcheverry, Guillermo; Zieher, Luis Marı́a

doi:10.1016/0006-8993(80)90049-9

Cited by 231 publications

(66 citation statements)

References 13 publications

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“…When administered systemically in rats, DSP-4 crosses the blood-brain barrier and causes rapid, profound, long-term decreases in NE and markers of noradrenergic function in the cortex but leaves hypothalamic NE function relatively unaltered [39,58]. These differential effects on NE function in the cortex and hypothalamus presumably result from DSP-4's high selectivity for noradrenergic axon terminals that originate in the LoC [33,34,37,39,57,58].…”

Section: Introductionmentioning

confidence: 99%

Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches

Waterman¹

2008

Behavioural Brain Research

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Section: Introductionmentioning

confidence: 99%

Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches

Waterman¹

2008

Behavioural Brain Research

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“…Systemic administration of N-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) produces a longterm disappearance of biochemical and histochemical markers for noradrenaline (NA) neurones in brain regions innervated by the locus coeruleus NA system in the mouse and rat (Ross 1976;Ross & Renyi 1976;Jaim-Etcheverry & Zieher 1980;Jonsson et al, 1981). These effects are most likely due to a DSP4-induced degeneration of NA nerve terminals.…”

Section: Introductionmentioning

confidence: 99%

A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurones in the CNS of the rat

Archer¹,

Jonsson

Ross³

1984

British J Pharmacology

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1 The effects of various doses of DSP4 on two-way active avoidance acquisition in rats and on central noradrenaline neurones were compared. 2 Doses of DSP4 from 3 mg kg-i.p. and upwards injected one week before the onset of the avoidance trials significantly impaired two-way avoidance learning. 3 The learning impairment caused by DSP4 (50mg kg-i.p.) lasted for at least 10 weeks. 4 Desipramine (20mg kg-1) injected either 30 or 60 min before DSP4 (50mg kg-1) antagonized the active avoidance impairment.5 A high dose of DSP4 (50mg kg-i.p.) produced profound decreases in dopamine-p-hydroxylase activity in the frontal cortex and in the concentrations of noradrenaline in various brain regions indicating degeneration of the locus coeruleus noradrenaline system. 6 Low doses of DSP4 (3 and 6mg kg Ii.p.) produced small but significant decreases in the concentrations of noradrenaline (NA) in some regions, e.g. cerebral cortex, hippocampus, olfactory bulb and spinal cord. 7 The avoidance impairment caused by the low dose of DSP4 (3 mg kg-) was absent when rats were tested 10 weeks after treatment nor was NA depletion present when NA was analysed 3 months after treatment.

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“…Neonatal treatment with neurotoxins, such as 6-hydroxydopamine (6-OHDA) or DSP-4 produces marked impairment in development of the central noradrenergic system, i.e., permanent and robust NE-denervation of the frontal cortex and spinal cord (Fig. 1a, c), accompanied by NE hyperinnervation of brainstem and cerebellum (Jaim-Etcheverry and Zieher 1980;Medina and Novas 1983). Neurotox Res (2013) 23:39-48 45 In the present study, destruction of noradrenergic neurons by DSP-4 significantly decreased the antinociceptive effect of methanandamide (10 mg/kg ip) in the tailimmersion test, hot-plate test, and writhing test (Figs.…”

Section: Discussionmentioning

confidence: 99%

Neonatal DSP-4 Treatment Modifies Antinociceptive Effects of the CB1-Receptor Agonist Methanandamide in Adult Rats

et al. 2012

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To study the influence of the central noradrenergic system on antinociceptive effects mediated by the CB 1 -receptor agonist methanandamide, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg sc 9 2, P1 and P3); zimelidine (10 mg/kg sc, 30 min pretreatment, selective serotonin reuptake inhibitor). When rats attained 10 weeks of age, monoamine and their metabolite concentrations were determined in the frontal cortex, thalamus, and spinal cord by an HPLC/ED method. Antinociceptive effects after methanandamide (10 mg/kg ip) apply were evaluated by a battery of tests. In addition, immunohistochemistry and densitometric analysis of the cannabinoid CB 1 receptor in the rat brain was performed. DSP-4 lesioning was associated with a reduction in norepinephrine content of the frontal cortex ([90 %) and spinal cord ([80 %) with no changes in the thalamus. Neonatal DSP-4 treatment produced a significant reduction in the antinociceptive effect of methanandamide in the tail-immersion test, hot-plate test and writhing tests. In the paw pressure and formalin hind paw tests results were ambiguous. These findings indicate that the noradrenergic system exerts a prominent influence on analgesia acting via the cannabinoid system in brain, without directly altering CB 1 receptor density in the brain.

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DSP-4: A novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats

Cited by 231 publications

References 13 publications

Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches

Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches

A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurones in the CNS of the rat

Neonatal DSP-4 Treatment Modifies Antinociceptive Effects of the CB1-Receptor Agonist Methanandamide in Adult Rats

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