Effects of central noradrenaline depletion by the selective neurotoxin DSP-4 on the behaviour of the isolated rat in the elevated plus maze and water maze

Lapiz, M.D.S.; Mateo, Yolanda; Durkin, Sean; Parker, Terry L.; Marsden, C.A.

doi:10.1007/s002130100702

Cited by 61 publications

(40 citation statements)

References 48 publications

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“…NA depletion did not affect nontransgenic animals, indicating that it is not sufficient to induce these behavioral alterations and memory deficits, as previously suggested (Sirvio et al, 1994;Lapiz et al, 2001). In contrast, NA-depleted APP23 mice showed a robust and significant increase in all radial arm maze parameters, committing significantly more working and reference memory errors than nondepleted APP23 mice.…”

Section: Discussionsupporting

confidence: 58%

“…Although selective lesioning of noradrenergic neurons with N- (2-chloroethyl)-N-ethyl-bromo-benzylamine (dsp4) does not affect working (Ohno et al, 1997) or spatial memory (Sirvio et al, 1994;Lapiz et al, 2001), it exacerbates memory deficits induced by blocking muscarinic acetylcholine receptors (Ohno et al, 1997). A recent study showed a facilitator role of NA in the retrieval of spatial and contextual memories within a limited time (Murchison et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice

et al. 2006

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Locus ceruleus (LC) degeneration and loss of cortical noradrenergic innervation occur early in Alzheimer's disease (AD). Although this has been known for several decades, the contribution of LC degeneration to AD pathogenesis remains unclear. We induced LC degeneration with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (dsp4) in amyloid precursor protein 23 (APP23) transgenic mice with a low amyloid load. Then 6 months later the LC projection areas showed a robust elevation of glial inflammation along with augmented amyloid plaque deposits. Moreover, neurodegeneration and neuronal loss significantly increased. Importantly, the paraventricular thalamus, a nonprojection area, remained unaffected. Radial arm maze and social partner recognition tests revealed increased memory deficits while high-resolution magnetic resonance imaging-guided micro-positron emission tomography demonstrated reduced cerebral glucose metabolism, disturbed neuronal integrity, and attenuated acetylcholinesterase activity. Nontransgenic mice with LC degeneration were devoid of these alterations. Our data demonstrate that the degeneration of LC affects morphology, metabolism, and function of amyloid plaque-containing higher brain regions in APP23 mice. We postulate that LC degeneration substantially contributes to AD development.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice

et al. 2006

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“…DSP-4 induces degradation of norepinephrine axons arising from the LC, while leaving brainstem norepinephrine innervation intact (Fritschy and Grzanna, 1989). The behavioral effects of DSP-4 treatment are variable (Harro et al, 1995;Lapiz et al, 2001;Itoi et al, 2011), and in our study, we found an anxiogenic effect in SD rats with no change in WKY rats relative to their respective controls. This LC inhibition also lowered the number of maze entries SD rats made to that of WKY.…”

Section: Discussionsupporting

confidence: 47%

“…The impact of DSP-4 lesioning on anxiety is dependent on dosage, recovery, and housing (Harro et al, 1995;Lapiz et al, 2001;Itoi et al, 2011). Our treatment increased anxiety-like behavior in SD rats, but not WKY rats as measured on the EPM.…”

Section: Coerulean Lesion Increased Anxiety-like Behavior In Sd Ratsmentioning

confidence: 76%

Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in Animals with Varied HPA Axis Function

Fox

Studebaker

Swofford

et al. 2015

Neuropsychopharmacol

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Previous work has demonstrated the importance of genetic factors and stress-sensitive circuits in the development of affective disorders. Anxiety and numerous psychological disorders are comorbid with substance abuse, and noradrenergic signaling in the bed nucleus of the stria terminalis (BNST) is thought to be a source of this convergence. Here, we examined the effects of different stressors on behavior and norepinephrine dynamics in the BNST of rat strains known to differ in their HPA-axis function. We compared the effects of acute morphine dependence and social isolation in non-anxious Sprague Dawley (SD) rats, and a depression model, Wistar-Kyoto (WKY) rats. We found a shared phenotype in drug-dependent and singly housed SD rats, characterized by slowed norepinephrine clearance, decreased autoreceptor function, and elevated anxiety. WKY rats exhibited changes in anxiety and autoreceptor function only following morphine dependence. To ascertain the influence of LC inhibition on this plasticity, we administered the LC-terminal-selective toxin DSP-4 to SD and WKY rats. DSP-4-treated SD rats demonstrated a dependence-like phenotype, whereas WKY rats were unchanged. Overall, our findings suggest that individuals with varying stress susceptibilities have different noradrenergic signaling changes in response to stress. These changes may establish conditions that favor stress-induced reinstatement and increase the risk for addiction.

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“…Its role during learning is illustrated by the observations that destruction of locus coeruleus neurons by DSP-4 treatment results in amnesia in day-old chicks [330] and impairment of memory for at least some tasks in rats [331][332][333]. A large amount of experimental evidence exists that administration of noradrenaline or β-adrenergic agonists enhances memory formation, whereas β-adrenergic receptor antagonists impair the acquisition of memory in a variety of tasks in both rats and chickens [rewieved in 334].…”

Section: Establishment Of Memorymentioning

confidence: 99%

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

Hertz¹,

Chen²,

Gibbs³

et al. 2004

CDTCNSND

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Considerable attention has recently been paid to astrocyte functions, which are briefly summarized. A large amount of data is available about adrenoceptor expression and function in astrocytes, some of it dating back to the 1970's and some of it very recent. This material is reviewed in the present paper. The brain is innervated by noradrenergic fibers extending from locus coeruleus in the brain stem, which in turn is connected to a network of adrenergic and noradrenergic nuclei in the medulla and pons, contributing to the control of (nor)adrenergic, serotonergic, dopaminergic and cholinergic function, both in the central nervous system (CNS) and in the periphery. In the CNS astrocytes constitute a major target for noradrenergic innervation, which regulates morphological plasticity, energy metabolism, membrane transport, gap junction permeability and immunological responses in these cells. Noradrenergic effects on astrocytes are essential during consolidation of episodal, long-term memory, which is reinforced by β-adrenergic activation. Glycogenolysis and synthesis of glutamate and glutamine from glucose, both of which are metabolic processes restricted to astrocytes, occurs at several time-specific stages during the consolidation. Astrocytic abnormalities are almost certainly important in the pathogenesis of multiple sclerosis and in all probability contribute essentially to inflammation and malfunction in Alzheimer's disease and to mood disturbances in affective disorders. Noradrenergic function in astrocytes is severely disturbed by chronic exposure to cocaine, which also changes astrocyte morphology. Development of drugs modifying noradrenergic receptor activity and/or down-stream signaling is advocated for treatment of several neurological/psychiatric disorders and for neuroprotection. Astrocytic preparations are suggested for study of mechanism(s) of action of antidepressant drugs and pathophysiology of mood disorders.

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Effects of central noradrenaline depletion by the selective neurotoxin DSP-4 on the behaviour of the isolated rat in the elevated plus maze and water maze

Cited by 61 publications

References 48 publications

Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice

Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice

Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in Animals with Varied HPA Axis Function

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

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