Novelty-oriented behavior in the rat after selective damage of locus coeruleus projections by DSP-4, a new noradrenergic neurotoxin

Delini‐Stula, A.; Mogilnicka, E; Hunn, C.; Dooley, David

doi:10.1016/0091-3057(84)90312-5

Cited by 68 publications

(30 citation statements)

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“…Previous behavioural studies have used 50 mg/kg dose or higher (for example, Delini-Stula et al 1984;Berridge and Dunn 1990;Harro et al 1995;Al-Zahrani et al 1997;Schuerger and Balaban 1999). However, with a 25 mg/kg dose, we achieved a decrease and rearing activity (C) after re-exposure to the LMA cages of DSP-4 or saline-treated group (G) and isolation-reared (I) rats expressed as mean beam breaks/min.…”

Section: Discussionmentioning

confidence: 92%

“…The ascending noradrenergic system from the locus coeruleus has been implicated in attention, arousal and exploratory behaviour, although there are conflicting findings on the effects of central noradrenaline (NA) depletion on these behaviours (Mason and Fibiger 1979;Archer et al 1983Archer et al , 1984Dooley et al 1983aDooley et al , 1983bDelini-Stula et al 1984;Harro et al 1995).…”

Section: Introductionmentioning

confidence: 99%

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Effects of noradrenaline depletion in the brain on response to novelty in isolation-reared rats

et al. 2000

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Effects of noradrenaline depletion in the brain on response to novelty in isolation-reared rats

et al. 2000

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“…There is considerable evidence that locus coeruleus denervation by DSP-4 treatment induces neophobia. DSP-4 treatment reduces the exploration of novel areas (Delini-Stula et al 1984;Harro et al 1995) and of a novel object in an open field (Mogilnicka et al 1985;Harro et al 1995), which can be reversed by diazepam treatment (Harro et al 1995). In more general terms, locus coeruleus denervation has been shown to reduce active behavioural strategies (Archer 1983;Archer et al 1984;Delini-Stula et al 1984;Harro et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Lesioning of Locus coeruleus Projections by DSP‐4 Neurotoxin Treatment: Effect on Amphetamine‐Induced Hyperlocomotion and Dopamine D₂ Receptor Binding in Rats

Harro

Meriküla

Lepiku

et al. 2000

Pharmacology & Toxicology

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DSP-4 is a neurotoxin highly selective for the noradrenergic nerve terminals of the locus coeruleus projections. Data on the effect of DSP-4 treatment on amphetamine-induced hyperlocomotion are contradictory. In this study, DSP-4 (50 mg/kg) caused reduction of noradrenaline levels by 70% in the cerebral cortex and by 79% in the cerebellum. This treatment resulted in upregulation of dopamine D 2 receptors in the striatum as evidenced by [ In an open field test, DSP-4 reduced locomotor activity. D-Amphetamine (1.5 mg/kg) caused a similar increase in locomotor activity in control and DSP-4-pretreated animals not familiar to the apparatus. However, when the rats were habituated to the test apparatus, the effect of amphetamine on horizontal activity was significantly larger in the DSP-4-pretreated animals. These data suggest that supersensitivity of D 2 receptors develops after locus coeruleus denervation, but that the enhanced efficacy of amphetamine in DSP-4-treated rats is masked by neophobia.After the first report on N(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) (Ross 1976), this neurotoxin has been widely used for selective destruction of the nerve terminals originating from the locus coeruleus (Jonsson et al. 1981;Fritschy & Grzanna 1989). Peripheral administration of DSP-4 depletes noradrenaline (NA) in the brain regions which are innervated by the locus coeruleus and it has no direct effect on serotonin and dopamine (DA) terminals in the rat (Ö gren et al. 1980;Chrobak et al. 1985;Harro et al. 1992;Somboonthum et al. 1997;Al-Zahrani et al. 1998;Hughes & Stanford 1998), even though some investigators have found small but significant reductions in 5-HT levels (Jonsson et al. 1982;Ohno et al. 1996).Previous studies have shown that DSP-4-induced lesions cause no gross changes in spontaneous behaviour (Jonsson et al. 1982), nor does treatment with the drug interfere with simple attentional tasks (Ruotsalainen et al. 1997). However, in more complex learning tasks, the locus coeruleusdenervated rats are less successful and the animals fail to engage in active behaviour necessary to cope with environmental changes (Archer 1983;Archer et al. 1984), possibly due to an increase in neophobia and some reduction in their motivation to explore (Harro et al. 1995).Contradictory data exist about the effect of locus coeruleus denervation by DSP-4 treatment on locomotor activity Author for correspondence: Jaanus Harro, Department of Psychology, University of Tartu, Tiigi 78, EE-50410 Tartu, Estonia (fax π372 7 375900, e-mail jharro/ut.ee).and amphetamine-induced hyperlocomotion. In early studies using 6-hydroxydopamine lesions of the NA-containing pathways, it was found that large NA depletions in several forebrain regions did not modify the locomotor stimulant effect of amphetamine (Hollister et al. 1974;Roberts et al. 1975). However, since the study of Ö gren et al. (1983), it is generally believed that the hyperactivity induced by amphetamine is significantly reduced after selective locus coeruleus denervatio...

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“…Norepinephrine (NE) is released in the hippocampus due to abundant noradrenergic input from the locus coeruleus (LC) (Loy et al, 1980) and has been shown to be involved in learning and memory (ini-Stula et al, 1984;Devauges and Sara, 1991;Roullet and Sara, 1998;Murchison et al, 2004;Tronel et al, 2004;Kemp and Manahan-Vaughan, 2008;Lemon et al, 2009) (for review, see (Sara, 2009). In the hippocampus, a key structure for the acquisition and consolidation of declarative memory traces, NE is released during novelty detection when neuronal activity is enhanced in the locus coeruleus (LC) (Sara et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Adrenergic modulation of sharp wave‐ripple activity in rat hippocampal slices

et al. 2011

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Norepinephrine (NE) has been shown to facilitate learning and memory by modulating synaptic plasticity in the hippocampus in vivo. During memory consolidation, transiently stored information is transferred from the hippocampus into the cortical mantle. This process is believed to depend on the generation of sharp wave-ripple complexes (SPW-Rs), during which previously stored information might be replayed. Here, we used rat hippocampal slices to investigate neuromodulatory effects of NE on SPW-Rs, induced by a standard long-term potentiation (LTP) protocol, in the CA3 and CA1. NE (10-50 μM) dose-dependently and reversibly suppressed the generation of SPW-Rs via activation of α1 adrenoreceptors, as indicated by the similar effects of phenylephrine (100 μM). In contrast, the unspecific β adrenoreceptor agonist isoproterenol (2 μM) significantly increased the incidence of SPW-Rs. Furthermore, β adrenoreceptor activation significantly facilitated induction of both LTP and SPW-Rs within the CA3 network. Suppression of SPW-Rs by NE was associated with a moderate hyperpolarization in the majority of CA3 pyramidal cells and with a reduction of presynaptic Ca(2+) uptake in the stratum radiatum. This was indicated by activity-dependent changes in [Ca(2+) ](o) and Ca(2+) fluorescence signals, by changes in the paired pulse ratio of evoked EPSPs and by analysis of the coefficient of variance. In the presence of NE, repeated high frequency stimulation (high-frequency stimulation (HFS)) failed to induce SPW-Rs, although SPW-Rs appeared following washout of NE. Together, our data indicate that the NE-mediated suppression of hippocampal SPW-Rs depends on α1 adrenoreceptor activation, while their expression and activity-dependent induction is facilitated via β1-adrenoreceptors.

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Novelty-oriented behavior in the rat after selective damage of locus coeruleus projections by DSP-4, a new noradrenergic neurotoxin

Cited by 68 publications

References 20 publications

Effects of noradrenaline depletion in the brain on response to novelty in isolation-reared rats

Effects of noradrenaline depletion in the brain on response to novelty in isolation-reared rats

Lesioning of Locus coeruleus Projections by DSP‐4 Neurotoxin Treatment: Effect on Amphetamine‐Induced Hyperlocomotion and Dopamine D₂ Receptor Binding in Rats

Adrenergic modulation of sharp wave‐ripple activity in rat hippocampal slices

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Novelty-oriented behavior in the rat after selective damage of locus coeruleus projections by DSP-4, a new noradrenergic neurotoxin

Cited by 68 publications

References 20 publications

Effects of noradrenaline depletion in the brain on response to novelty in isolation-reared rats

Effects of noradrenaline depletion in the brain on response to novelty in isolation-reared rats

Lesioning of Locus coeruleus Projections by DSP‐4 Neurotoxin Treatment: Effect on Amphetamine‐Induced Hyperlocomotion and Dopamine D2 Receptor Binding in Rats

Adrenergic modulation of sharp wave‐ripple activity in rat hippocampal slices

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Lesioning of Locus coeruleus Projections by DSP‐4 Neurotoxin Treatment: Effect on Amphetamine‐Induced Hyperlocomotion and Dopamine D₂ Receptor Binding in Rats