Biochemical and radioautographic evidence for dopaminergic afferents of the locus coeruleus originating in the ventral tegmental area

Ornstein, Kurt; Milon, H.; McRae-Degueurce, A.; Alvarez, Chantal; Berger, Brigitte; Hp, Würzner

doi:10.1007/bf01253597

Cited by 59 publications

(36 citation statements)

References 17 publications

(17 reference statements)

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“…The dopamine transporter (Freeman et al, 2001) and D 1 and D 2 dopamine receptors (Huang et al, 1992;Lewis and O'Donnell, 2000) are present in both the thalamus and the cerebral cortex, suggesting that dopamine can directly influence thalamocortical activity. Our study also confirms the vPAG dopaminergic projections to the basal forebrain cholinergic cells (Eberhart et al, 1985;Semba et al, 1988), the noradrenergic LC (Ornstein et al, 1987), and the DRN (Kalen et al, 1988), as well as demonstrating these inputs to the lateral hypothalamic orexin cells, the LDT cholinergic cells, and to the VLPO. These projections provide a number of potential sites at which DA may influence sleep-wake regulation.…”

Section: Technical Considerationsupporting

confidence: 82%

Identification of Wake-Active Dopaminergic Neurons in the Ventral Periaqueductal Gray Matter

Lü

Jhou²,

Saper³

2006

J. Neurosci.

410

309

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Recent evidence suggests that dopamine plays an important role in arousal, but the location of the dopaminergic neurons that may regulate arousal remains unclear. It is sometimes assumed that the dopaminergic neurons in the ventral tegmental area that project to the prefrontal cortex and striatum may regulate the state of arousal; however, the firing of these dopaminergic neurons does not correlate with overall levels of behavioral wakefulness. We identified wake-active dopaminergic neurons by combining immunohistochemical staining for Fos and tyrosine hydroxylase (TH) in awake and sleeping rats. Approximately 50% of the TH-immunoreactive (TH-ir) cells in the ventral periaqueductal gray matter (vPAG) expressed Fos protein during natural wakefulness or wakefulness induced by environmental stimulation, but none expressed Fos during sleep. Fos immunoreactivity was not seen in the substantia nigra TH-immunoreactive cells in either condition. Injections of 6-hydroxydopamine into the vPAG, which killed 55-65% of wake-active TH-ir cells but did not injure nearby serotoninergic cells, increased total daily sleep by ϳ20%. By combining retrograde and anterograde tracing, we showed that these wake-active dopaminergic cells have extensive reciprocal connections with the sleep-wake regulatory system. The vPAG dopaminergic cells may provide the long-sought ascending dopaminergic waking influence. In addition, their close relationship with the dorsal raphe nucleus will require reassessment of previous studies of the role of the dorsal raphe nucleus in sleep, because many of those experiments may have been confounded by the then-unrecognized presence of intermingled wake-active dopaminergic neurons.

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Section: Technical Considerationsupporting

confidence: 82%

Identification of Wake-Active Dopaminergic Neurons in the Ventral Periaqueductal Gray Matter

Lü

Jhou²,

Saper³

2006

J. Neurosci.

410

309

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“…Release of catecholamines in the locus coeruleus of freely moving and anaesthetized normotensive and spontaneously hypertensive rats: effects of cardiovascular changes and tail pinch ergic cell bodies located in and around the posterior hypothalamic area (Maeda et al 1991) and the ventral tegmental area (Ornstein et al 1987).…”

Section: Stefan T Kaehler · Catrin Sinner · Athineos Philippumentioning

confidence: 99%

Release of catecholamines in the locus coeruleus of freely moving and anaesthetized normotensive and spontaneously hypertensive rats: effects of cardiovascular changes and tail pinch

Kaehler

Sinner

Philippu

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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Noradrenaline turnover has been found to be increased in the locus coeruleus of young spontaneously hypertensive rats (SHR). There is also evidence that the noradrenergic projection from the locus coeruleus to the posterior hypothalamus contributes to the development of genetic hypertension. To investigate whether the release of noradrenaline and dopamine in the locus coeruleus is modified in genetic hypertension, this brain region of adult SHR and normotensive Wistar-Kyoto (WKY) rats was superfused with artificial cerebrospinal fluid through a push-pull cannula. Dopamine and noradrenaline released in the superfusate were determined radioenzymatically. There was no difference in the basal release of noradrenaline and dopamine in the locus coeruleus of conscious, anaesthetized or diazepam-treated adult WKY rats and SHR. In conscious animals, a rise in blood pressure elicited by intravenous infusion of phenylephrine enhanced the release of noradrenaline and dopamine in both strains to the same extent. Intravenous infusion of sodium nitroprusside elicited a fall in blood pressure and also increased to the same degree the release of noradrenaline and dopamine in the locus coeruleus of normotensive and hypertensive conscious rats. In anaesthetized rats, baroreceptor activation by phenylephrine decreased the release of noradrenaline and dopamine, while sodium nitroprusside lowered blood pressure and enhanced the release rates of the two catecholamines. Treatment of conscious rats with diazepam (10 mg/kg, i.p., 120 min prior to starting collection of the superfusate) abolished the phenylephrine-evoked release of catecholamines observed in conscious animals. The sensory stimulus tail pinch led to a slight increase in blood pressure. In conscious animals, this aversive stimulus led to enhanced release of noradrenaline and dopamine that lasted longer in SHR than in WKY rats. The release of catecholamines evoked by tail pinch was abolished in rats treated with diazepam, as well as in anaesthetized animals. Our findings show that in adult rats, genetic hypertension does not modify the release of noradrenaline and dopamine in the locus coeruleus. Since in anaesthetized rats increases in blood pressure diminish, while decreases in blood pressure enhance, the release of noradrenaline and dopamine, it seems that both amines possess a counteracting, hypertensive function in the rat locus coeruleus. When baroreceptor activation by phenylephrine is carried out on conscious animals, stress predominates and the release of catecholamines is enhanced. This study demonstrates the importance of the noradrenergic system of the locus coeruleus in central cardiovascular control and in emotional, stress and pain-regulating processes.

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“…Anatomical data support this possibility because descending pathways from the VTA innervate the LC (Ornstein et al, 1987). Moreover, in rodents, although only a small percentage of its VTA-derived afferents seem to be dopaminergic (Swanson, 1982), DA receptors mainly of the D 2 -like subtype have been identified in the LC (Yokoyama et al, 1994).…”

mentioning

confidence: 99%

Cross-Talk between Dopaminergic and Noradrenergic Systems in the Rat Ventral Tegmental Area, Locus Ceruleus, and Dorsal Hippocampus

Guiard

Mansari²,

Blier³

2008

Mol Pharmacol

132

114

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A decreased central dopaminergic and/or noradrenergic transmission is believed to be involved in the pathophysiology of depression. It is known that dopamine (DA) neurons in the ventral tegmental area (VTA) and norepinephrine (NE) neurons in the locus ceruleus (LC) are autoregulated by somatodendritic D 2 -like and ␣ 2 -adrenoceptors, respectively. Complementing these autoreceptor-mediated inhibitory feedbacks, anatomical and functional studies have established a role for noradrenergic inputs in regulating dopaminergic activity, and reciprocally. In the present study, a microiontophoretic approach was used to characterize the postsynaptic catecholamine heteroreceptors involved in such regulations. In the VTA, the application of DA and NE significantly reduced the firing activity of DA neurons. In addition to a role for D 2 -like receptors in the inhibitory effects of both catecholamines, it was demonstrated that the ␣ 2 -adrenoceptor antagonist idazoxan dampened the DA-and NE-induced attenuations of DA neuronal activity, indicating that both of these receptors are involved in the responsiveness of VTA DA neurons to catecholamines. In the LC, the effectiveness of iontophoretically applied NE and DA to suppress NE neuronal firing was blocked by idazoxan but not by the D 2 -like receptor antagonist raclopride, which suggested that only ␣ 2 -adrenoceptors were involved. In the dorsal hippocampus, a forebrain region having a sparse dopaminergic innervation but receiving a dense noradrenergic input, the suppressant effects of DA and NE on pyramidal neurons were attenuated by idazoxan but not by raclopride. The suppressant effect of DA was prolonged by administration of the selective NE reuptake inhibitor desipramine and, to lesser extent, of the selective DA reuptake inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)-piperazine (GBR12909), suggesting that both the NE and DA transporters were involved in DA uptake in the hippocampus. These findings might help in designing new antidepressant strategies aimed at enhancing DA and NE neurotransmission.The catecholamines neurotransmitters dopamine (DA) and norepinephrine (NE) are believed to be involved in psychiatric disorders, and a better knowledge of the reciprocal interactions between these two systems should improve our understanding of the pathophysiology and treatment of mood disorders. Anatomical evidence indicates that noradrenergic neurons of the locus ceruleus (LC) send projections to the ventral tegmental area (VTA) in the vicinity of DA neuron cell bodies (Simon et al., 1979). Several subtypes of ␣-adrenergic receptors have been identified in the VTA (Lee et al., 1998), raising the possibility that NE inputs play a role in modulating DA neuronal activity. Consistent with this assumption, it was recently demonstrated that a selective lesion of LC NE neurons increases the mean firing activity of DA neurons by 70% and their burst activity by almost 50%, thus revealing a net inhibitory effect of NE in the VTA (Guiard et al., 2008). In con...

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Biochemical and radioautographic evidence for dopaminergic afferents of the locus coeruleus originating in the ventral tegmental area

Cited by 59 publications

References 17 publications

Identification of Wake-Active Dopaminergic Neurons in the Ventral Periaqueductal Gray Matter

Identification of Wake-Active Dopaminergic Neurons in the Ventral Periaqueductal Gray Matter

Release of catecholamines in the locus coeruleus of freely moving and anaesthetized normotensive and spontaneously hypertensive rats: effects of cardiovascular changes and tail pinch

Cross-Talk between Dopaminergic and Noradrenergic Systems in the Rat Ventral Tegmental Area, Locus Ceruleus, and Dorsal Hippocampus

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