Denervation of the locus coeruleus projections by treatment with the selective neurotoxin DSP-4 [N (2-chloroethyl)-N-ethyl-2-bromobenzylamine] reduces dopamine release potential in the nucleus accumbens shell in conscious rats

Häidkind, Riina; Kivastik, Toomas; Eller, Marika; Kolts, Ivo; Oreland, Lars; Harro, Jaanus

doi:10.1016/s0304-3940(02)00817-0

Cited by 15 publications

(3 citation statements)

References 16 publications

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“…Consistent with these results, LC lesions decrease striatal DA availability (Russell et al, 1989;Lategan et al, 1990Lategan et al, , 1992Haidkind et al, 2002), resulting in DA receptor supersensitivity (Donaldson et al, 1976;Lategan et al, 1989;Harro et al, 2000). Basal DA release in the PFC was not significantly affected, suggesting that NE is more critical for the basal tone of mesolimbic and nigrostriatal DA neurons than for mesocortical DA neurons.…”

Section: Regulation Of Da Release By Nementioning

confidence: 73%

Dopamine β-Hydroxylase Knockout Mice have Alterations in Dopamine Signaling and are Hypersensitive to Cocaine

Schank

Ventura

Puglisi-Allegra

et al. 2005

Neuropsychopharmacol

119

117

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Multiple lines of evidence demonstrate that the noradrenergic system provides both direct and indirect excitatory drive onto midbrain dopamine (DA) neurons. We used DA b-hydroxylase (DBH) knockout (DbhÀ/À) mice that lack norepinephrine (NE) to determine the consequences of chronic NE deficiency on midbrain DA neuron function in vivo. Basal extracellular DA levels were significantly attenuated in the nucleus accumbens (NAc) and caudate putamen (CP), but not prefrontal cortex (PFC), of DbhÀ/À mice, while amphetamine-induced DA release was absent in the NAc and attenuated in the CP and PFC. The decrease in dopaminergic tone was associated with a profound increase in the density of high-affinity state D 1 and D 2 DA receptors in the NAc and CP, while DA receptors in the PFC were relatively unaffected. As a behavioral consequence of these neurochemical changes, DbhÀ/À mice were hypersensitive to the psychomotor, rewarding, and aversive effects of cocaine, as measured by locomotor activity and conditioned place preference. Antagonists of DA, but not 5-HT, receptors attenuated the locomotor hypersensitivity to cocaine in DbhÀ/À mice. As DBH activity in humans is genetically controlled and the DBH inhibitor disulfiram has shown promise as a pharmacotherapy for cocaine dependence, these results have implications for the influence of genetic and pharmacological DBH inhibition on DA system function and drug addiction.

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Section: Regulation Of Da Release By Nementioning

confidence: 73%

Dopamine β-Hydroxylase Knockout Mice have Alterations in Dopamine Signaling and are Hypersensitive to Cocaine

Schank

Ventura

Puglisi-Allegra

et al. 2005

Neuropsychopharmacol

119

117

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“…Chemical lesions of the LC or its afferents decreased DA levels in the NAcc, caudate, and prefrontal cortex (PFC) (Carboni et al, 1990; Haidkind et al, 2002; Lategan et al, 1990; Lategan et al, 1992; Masana et al, 2011). Similarly, chronic inhibition of NE synthesis by genetic lesion of DA-beta hydroxylase (DBH), the enzyme responsible for converting DA into NE in adrenergic neurons, also decreased DA levels in NAcc and caudate-putamen, but not in the PFC (Schank et al, 2006).…”

Section: Regulation Of Da Release By the Adrenergic Systemmentioning

confidence: 99%

Specificity and impact of adrenergic projections to the midbrain dopamine system

Mejías-Aponte

2016

Brain Research

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Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson’s disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system.

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“…The mechanism underlying this phenomenon appears to be compensatory sprouting by surviving LC neurons [46], reminiscent of the compensation by remaining NE terminals observed in rodents with LC lesions [47]. However, it is important to bear in mind that, while their basal extracellular NE levels are normal, LC-lesioned animals have profound noradrenergic deficiencies when challenged neurochemically or behaviorally [48][49][50], even when the lesions are quite modest [51]. In addition, the sprouting of surviving LC neurons in AD may produce abnormal connections, leading to improper NE signaling.…”

Section: Lc Loss and Alzheimer's Disease: Clinical Implicationsmentioning

confidence: 99%

Functional Consequences of Locus Coeruleus Degeneration in Alzheimers Disease

Weinshenker

2008

CAR

171

142

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Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients, and its prevalence is expected to soar in coming decades. Neuropathologically, AD is characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, and cholinergic neuronal loss. In addition to the hallmark of memory loss, the disease is associated with other neuropsychiatric and behavioral abnormalities, including psychosis, aggression, and depression. Although cholinergic cell loss is clearly an important attribute of the pathological process, another well-described yet underappreciated early feature of AD pathogenesis is degeneration of the locus coeruleus (LC), which serves as the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The purpose of this review is to explore the extent to which LC loss contributes to AD neuropathology and cognitive deficits.

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Denervation of the locus coeruleus projections by treatment with the selective neurotoxin DSP-4 [N (2-chloroethyl)-N-ethyl-2-bromobenzylamine] reduces dopamine release potential in the nucleus accumbens shell in conscious rats

Cited by 15 publications

References 16 publications

Dopamine β-Hydroxylase Knockout Mice have Alterations in Dopamine Signaling and are Hypersensitive to Cocaine

Dopamine β-Hydroxylase Knockout Mice have Alterations in Dopamine Signaling and are Hypersensitive to Cocaine

Specificity and impact of adrenergic projections to the midbrain dopamine system

Functional Consequences of Locus Coeruleus Degeneration in Alzheimers Disease

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