1,721,031 research outputs found
On the origin of cortical dopamine: Is it a co-transmitter in noradrenergic neurons?
No full textDopamine (DA) and noradrenaline (NA) in the prefrontal cortex (PFC) modulate superior cognitive functions, and are involved in the aetiology of depressive and psychotic symptoms. Moreover, microdialysis studies in rats have shown how pharmacological treatments that induce modifications of extracellular NA in the medial PFC (mPFC), also produce parallel changes in extracellular DA. To explain the coupling of NA and DA changes, this article reviews the evidence supporting the hypothesis that extracellular DA in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for NA and as a co-transmitter. Accordingly, extracellular DA concentration in the occipital, parietal and cerebellar cortex was found to be much higher than expected in view of the scarce dopaminergic innervation in these areas. Systemic administration or intra-cortical perfusion of α2-adrenoceptor agonists and antagonists, consistent with their action on noradrenergic neuronal activity, produced concomitant changes not only in extracellular NA but also in DA in the mPFC, occipital and parietal cortex. Chemical modulation of the locus coeruleus by locally applied carbachol, kainate, NMDA or clonidine modified both NA and DA in the mPFC. Electrical stimulation of the locus coeruleus led to an increased efflux of both NA and DA in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone was enhanced. Atypical antipsychotics, such as clozapine and olanzapine, or antidepressants, including mirtazapine and mianserine, have been found to increase both NA and DA throughout the cerebral cortex, likely through blockade of α2-adrenoceptors. On the other hand, drugs selectively acting on dopaminergic transmission produced modest changes in extracellular DA in mPFC, and had no effect on the occipital or parietal cortex. Acute administration of morphine did not increase DA levels in the PFC (where NA is diminished), in contrast with augmented dopaminergic neuronal activity; moreover, during morphine withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic activity, both increases being antagonised by clonidine but not quinpirole administration. Extensive 6-hydroxy dopamine lesion of the ventral tegmental area (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC in the nucleus accumbens, but only partially or not significantly in the mPFC and parietal cortex. The above evidence points to a common origin for NA and DA in the cerebral cortex and suggests the possible utility of noradrenergic system modulation as a target for drugs with potential clinical efficacy on cognitive functions
Evidence that cortical dopamine is a co-transmitter in noradrenergic neurons
No full textDopamine and noradrenaline in the prefrontal cortex modulate superior cognitive functions and are implicated in the aetiology of depressive and psychotic symptoms. Experimental evidence reveals parallel variations in extracellular concentration of both catecholamines in the cerebral cortex. In this review, data are presented suggesting that extracellular dopamine in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for noradrenaline and as co-transmitter. Since there lease of noradrenaline is controlled by alpha2-autoreceptors, it follows that release and extracellular concentration of both dopamine and noradrenaline in the cerebral cortex are controlled by alpha2-autoreceptors and noradrenaline transporter, whereas dopamine receptors and dopamine transporter do not seem to be involved in these processes. Atypical antipsychotics such as clozapine, and antidepressants such as mirtazapine, increase noradrenaline and dopamine release throughout the cerebral cortex, but not, or to a lesser extent, in subcortical areas. On the other hand, D2 selective drugs such as haloperidol, are potent in increasing dopamine levels in subcortical dopaminergic areas but are ineffective on dopamine and noradrenaline levels in the prefrontal cortex. Local stimulation or inhibition of locus coeruleus neurons by means of drug perfusion or electrical stimulation gives rise to parallel variations of noradrenaline and dopamine levels in the cerebral cortex, but not in prevalently dopaminergic subcortical areas. Extracellular dopamine of noradrenergic origin might represent the major portion of total extracellular dopamine not only in cortices with scarce dopaminergic innervation, such as the parietal and occipital cortex, but also in the densely innervated medial prefrontal cortex. In conclusion, drugs acting on the co-release mechanism of noradrenaline and dopamine may represent a tool with which to increase the selective output of dopamine in the cerebral cortex
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Nitrergic system and plasmatic methylarginines: Evidence of their role in the perinatal programming of cardiovascular diseases
No full textAtherosclerosis, in turn preceded by endothelial dysfunction, underlies a series of important cardiovascular diseases. Reduced bioavailability of endothelial nitric oxide, by increasing vascular tone and promoting platelet aggregation, leukocyte adhesion, and smooth muscle cell proliferation, plays a key role in the onset of the majority of cardiovascular diseases. In addition, high blood levels of asymmetric dimethylarginine, a potent inhibitor of nitric oxide synthesis, are associated with future development of adverse cardiovascular events and cardiac death. Recent reports have demonstrated that another methylarginine, i.e., symmetric dimethylarginine, is also involved in the onset of endothelial dysfunction and hypertension. Almost a decade ago, prematurity at birth and intrauterine growth retardation were first associated with a potential negative influence on the cardiovascular apparatus, thus constituting risk factors or leading to early onset of cardiovascular diseases. This condition is referred to as cardiovascular perinatal programming. Accordingly, cardiovascular morbidity and mortality are higher among former preterm adults than in those born at term. The aim of this paper was to undertake a comprehensive literature review focusing on cellular and biochemical mechanisms resulting in both reduced nitric oxide bioavailability and increased methylarginine levels in subjects born preterm. Evidence of the involvement of these compounds in the perinatal programming of cardiovascular risk are also discussed
Stimulation of the locus coeruleus elicits noradrenaline and dopamine release in the medial prefrontal and parietal cortex
No full textOur previous studies have suggested that dopamine and noradrenaline may be coreleased from noradrenergic nerve terminals in the cerebral cortex. To further clarify this issue, the effect of electrical stimulation of the locus coeruleus on extracellular noradrenaline, dopamine and DOPAC in the medial prefrontal cortex, parietal cortex and caudate nucleus was analysed by microdialysis in freely moving rats. Stimulation of the locus coeruleus for 20 min with evenly spaced pulses at 1 Hz failed to modify cortical catecholamines and DOPAC levels. Stimulation with bursts of pulses at 12 and 24 Hz increased, in a frequency-related manner, not only noradrenaline but also dopamine and DOPAC in the two cortices. In both cortices noradrenaline returned to baseline within 20 min of stimulation, irrespective of the stimulation frequency, whereas dopamine returned to normal within 20 and 60 min in the medial prefrontal cortex and within 60 and 80 min in the parietal cortex after 12 and 24 Hz stimulation, respectively. DOPAC remained elevated throughout the experimental period. Phasic stimulation of the locus coeruleus at 12 Hz increased noradrenaline in the caudate nucleus as in the cerebral cortices but was totally ineffective on dopamine and DOPAC. Tetrodotoxin perfusion into the medial prefrontal cortex dramatically reduced noradrenaline and dopamine levels and suppressed the effect of electrical stimulation. These results indicate that electrical stimulation-induced increase of dopamine is a nerve impulse exocytotic process and suggest that cortical dopamine and noradrenaline may be coreleased from noradrenergic terminals
Alpha2-adrenoceptor mediated co-release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex
No full textPrevious results suggest that extracellular dopamine (DA) in
the rat cerebral cortex originates from dopaminergic and
noradrenergic terminals. To further clarify this issue, dialysate
DA, dihydroxyphenylacetic acid (DOPAC) and noradrenaline
(NA) were measured both in the medial prefrontal cortex
(mPFC) and in the occipital cortex (OCC), with dense and
scarce dopaminergic projections, respectively. Moreover, the
effect of the a2-adrenoceptor antagonist RS 79948 and the
D2-receptor antagonist haloperidol on extracellular DA, DOPAC
and NA was investigated. Extracellular DA and DOPAC
concentrations in the OCC were 43% and 9%, respectively,
those in the mPFC. Haloperidol (0.1 mg/kg i.p.) increased DA
and DOPAC (by 35% and 150%, respectively) in the mPFC,
but was ineffective in the OCC. In contrast, RS 79948
(1.5 mg/kg i.p.) increased NA, DA and DOPAC, both in the
mPFC (by approximately 50%, 60% and 130%, respectively)
and the OCC (by approximately 50%, 80% and 200%,
respectively). Locally perfused, the DA transporter blocker
GBR 12909 (10 lM) was ineffective in either cortex, whereas
desipramine (DMI, 100 lM) markedly increased extracellular
NA and DA in both cortices. The weak haloperidol effect on
DA efflux was not enhanced after DA- and NA-transporter
blockade, whereas after DMI, RS 79948 markedly increased
extracellular NA, and especially DA and DOPAC in both cortices.
The results support the hypothesis that most extracellular
DA in the cortex is co-released with NA from
noradrenergic terminals, such co-release being primarily
controlled by a2-adrenoceptors
- …
