| 1. |
- Anderberg, Rozita H, 1976, et al.
(author)
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Dopamine signaling in the amygdala, increased by food ingestion and GLP-1, regulates feeding behavior.
- 2014
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In: Physiology & behavior. - : Elsevier BV. - 1873-507X .- 0031-9384. ; 136, s. 135-144
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Journal article (peer-reviewed)abstract
- Mesolimbic dopamine plays a critical role in food-related reward processing and learning. The literature focuses primarily on the nucleus accumbens as the key dopaminergic target in which enhanced dopamine signaling is associated with reward. Here, we demonstrate a novel neurobiological mechanism by which dopamine transmission in the amygdala regulates food intake and reward. We show that food intake was associated with increased dopamine turnover in the amygdala. Next, we assess the impact of direct intra-amygdala D1 and D2 receptor activation on food intake and sucrose-driven progressive ratio operant conditioning in rats. Amygdala D2 receptor activation reduced food intake and operant behavior for sucrose, whereas D2 receptor blockade increased food intake but surprisingly reduced operant behavior. In contrast, D1 receptor stimulation or blockade did not alter feeding or operant conditioning for food. The glucagon-like peptide 1 (GLP-1) system, a target for type 2 diabetes treatment, in addition to regulating glucose homeostasis, also reduces food intake. We found that central GLP-1R receptor activation is associated with elevated dopamine turnover in the amygdala, and that part of the anorexic effect of GLP-1 is mediated by D2 receptor signaling in the amygdala. Our findings indicate that amygdala dopamine signaling is activated by both food intake and the anorexic brain-gut peptide GLP-1 and that amygdala D2 receptor activation is necessary and sufficient to change feeding behavior. Collectively these studies indicate a novel mechanism by which the dopamine system affects feeding-oriented behavior at the level of the amygdala.
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| 2. |
- Andersson, Daniel, et al.
(author)
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Motor activity-induced dopamine release in the substantia nigra is regulated by muscarinic receptors.
- 2010
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In: Experimental neurology. - : Elsevier BV. - 1090-2430 .- 0014-4886. ; 221:1, s. 251-259
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Journal article (peer-reviewed)abstract
- Nigro-striatal neurons release dopamine not only from their axon terminals in the striatum, but also from somata and dendrites in the substantia nigra. Somatodendritic dopamine release in the substantia nigra can facilitate motor function by mechanisms that may act independently of axon terminal dopamine release in the striatum. The dopamine neurons in the substantia nigra receive a cholinergic input from the pedunculopontine nucleus. Despite recent efforts to introduce this nucleus as a potential target for deep brain stimulation to treat motor symptoms in Parkinson's disease; and the well-known antiparkinsonian effects of anticholinergic drugs; the cholinergic influence on somatodendritic dopamine release is not well understood. The aim of this study was to investigate the possible regulation of locomotor-induced dopamine release in the substantia nigra by endogenous acetylcholine release. In intact and 6-OHDA hemi-lesioned animals alike, the muscarinic antagonist scopolamine, when perfused in the substantia nigra, amplified the locomotor-induced somatodendritic dopamine release to approximately 200% of baseline, compared to 120-130% of baseline in vehicle-treated animals. A functional importance of nigral muscarinic receptor activation was demonstrated in hemi-lesioned animals, where motor performance was significantly improved by scopolamine to 82% of pre-lesion performance, as compared to 56% in vehicle-treated controls. The results indicate that muscarinic activity in the substantia nigra is of functional importance in an animal Parkinson's disease model, and strengthen the notion that nigral dopaminergic regulation of motor activity/performance is independent of striatal dopamine release.
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| 3. |
- Bergquist, Filip, 1970, et al.
(author)
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Can Objective Measurements Improve Treatment Outcomes in Parkinson’s Disease?
- 2014
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In: European Neurological Review. - 1758-3837. ; 9:1, s. 27-30
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Journal article (other academic/artistic)abstract
- Many examples in medicine show that therapies are most effective when measurement is used to guide their implementation, dose and effects. There are effective symptomatic therapies for the motor symptoms of Parkinson’s disease, which improve quality of life and have a health economic justification for their subsidisation. As measurement should lead to more effective deployment of these therapies, even in a percentage of cases, then costs of therapy would be reduced and by that percentage. We conclude that there is a clear need for continuous objective measures of dyskinesia and bradykinesia while patients go about their normal daily activities. The benefit of measurement would be greatest if these measures were directed at treating fluctuations.
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| 4. |
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| 5. |
- Dickson, Suzanne L., 1966, et al.
(author)
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The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors.
- 2012
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In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:14, s. 4812-20
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Journal article (peer-reviewed)abstract
- The glucagon-like peptide 1 (GLP-1) system is a recently established target for type 2 diabetes treatment. In addition to regulating glucose homeostasis, GLP-1 also reduces food intake. Previous studies demonstrate that the anorexigenic effects of GLP-1 can be mediated through hypothalamic and brainstem circuits which regulate homeostatic feeding. Here, we demonstrate an entirely novel neurobiological mechanism for GLP-1-induced anorexia in rats, involving direct effects of a GLP-1 agonist, Exendin-4 (EX4) on food reward that are exerted at the level of the mesolimbic reward system. We assessed the impact of peripheral, central, and intramesolimbic EX4 on two models of food reward: conditioned place preference (CPP) and progressive ratio operant-conditioning. Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets. EX4 also decreased motivated behavior for sucrose in a progressive ratio operant-conditioning paradigm when administered peripherally. We show that this effect is mediated centrally, via GLP-1 receptors (GLP-1Rs). GLP-1Rs are expressed in several key nodes of the mesolimbic reward system; however, their function remains unexplored. Thus we sought to determine the neurobiological substrates underlying the food-reward effect. We found that the EX4-mediated inhibition of food reward could be driven from two key mesolimbic structures-ventral tegmental area and nucleus accumbens-without inducing concurrent malaise or locomotor impairment. The current findings, that activation of central GLP-1Rs strikingly suppresses food reward/motivation by interacting with the mesolimbic system, indicate an entirely novel mechanism by which the GLP-1R stimulation affects feeding-oriented behavior.
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| 6. |
- Lindgren, H. S., et al.
(author)
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The effect of additional noradrenergic and serotonergic depletion on a lateralised choice reaction time task in rats with nigral 6-OHDA lesions
- 2014
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In: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 253, s. 52-62
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Journal article (peer-reviewed)abstract
- Parkinson's disease (PD) patients often suffer from visuospatial deficits, which have been considered a disruption of the representation of external space. The lateralised choice reaction time (CRT) task is an operant task for rodents in which similar deficits can be assessed. It has been demonstrated that specific parameters in this task is disrupted after unilateral injections of 6-hydroxydopamine (6-OHDA), which have been associated with the dopamine (DA) depletion that inevitably follows this type of lesion. However, studies have demonstrated that this type of lesion also affects the serotonergic (5HT) and noradrenergic (NA) systems. However, the impact of these systems on parameters in the CRT task had not yet been investigated.To this end, rats were pretrained on the CRT task before receiving selective lesions of the DAergic system, either alone or in combination with depletion of the NA or 5HT system. All rats with a 6-OHDA lesion displayed a gradual decline in the selection, initiation and execution of lateralised movements compared to sham-lesion controls on the side contralateral to the lesion. They also displayed a reduced number of useable trials as well as an increased number of procedural errors. Interestingly, the group with an additional noradrenergic lesion was significantly slower in reacting to lateralised stimuli throughout the testing period compared to the other two groups with a 6-OHDA lesion. There was however no difference between the three different lesion groups in the other parameters assessed in the task.These data confirm previous findings demonstrating that the majority of the parameters assessed in the lateralised CRT task are strongly dependent on DA. However, this study has also shown that the NAergic system may play an important role in contributing to the attentive performance influencing the capacity to react to the presented lateralised stimuli. © 2013 Elsevier Inc.
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| 7. |
- Nilsson, Manja C. A., 1966-, et al.
(author)
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Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction in anesthetized pigs, without affecting the endogenous pulmonary nitric oxide production.
- 2012
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 38:3, s. 509-517
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Journal article (peer-reviewed)abstract
- Purpose Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs. Methods Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO2) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. Results There were no differences between the groups for ENO, Ca2+-independent or Ca2+-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (Q LLL/Q T) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, Q LLL/Q T increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where Q LLL/Q T remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO2 (p < 0.01). Conclusions Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.
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| 8. |
- Nilsson, Manja, et al.
(author)
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Distant effects of nitric oxide inhalation in lavage induced lung injury in anaesthetised pigs
- 2013
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 57:3, s. 326-333
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Journal article (peer-reviewed)abstract
- Background Inhalation of nitric oxide (INO) exerts both local and distanteffects. INO in healthy pigs causes down-regulation of endogenous nitric oxide(NO) production and vasoconstriction in lung regions not reached by INO, especially in hypoxic regions, which augments hypoxic pulmonary vasoconstriction. In contrast, in pigs with endotoxemia-induced lung injury, INO causes increased NO production in lung regions not reached by INO. The aim ofthis study was to investigate whether INO exerts distant effects in surfactant-depleted lungs. Methods Twelve pigs were anaesthetised, and the left lower lobe (LLL) was separately ventilated. Lavage injury was induced in all lung regions, except the LLL. In six pigs, 40 ppm INO was given to the LLL (INO group), and theeffects on endogenous NO production and blood flow in the lavage-injured lungregions were studied. Six pigs served as a control group. NO concentration inexhaled air (ENO), NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. Results The calcium (Ca2+)-dependent NOS activity was lower (P<0.05) in the lavage-injured lung regions in the INO group than in the control group. There were no measurable differences between the groups for Ca2+-independent NOS activity, cGMP, ENO, or regional pulmonary blood flow. Conclusions Regional INO did not increase endogenous NO production in lavage-injured lung regions not directly reached by INO, but instead down-regulated the constitutive calcium-dependent nitric oxide synthase activity, indicating that NO may inhibit its own synthesis.
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| 9. |
- Pålsson, Erik, 1975, et al.
(author)
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Noise benefit in prepulse inhibition of the acoustic startle reflex
- 2011
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 214:3, s. 675-685
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Journal article (peer-reviewed)abstract
- Under some conditions, external sensory noise enhances cognitive functions, a phenomenon possibly involving stochastic resonance and/or enhanced central dopamine transmission. Prepulse inhibition (PPI) of the startle reflex is a robust measure of sensorimotor gating and can be modulated by activity in the cortex and basal ganglia, including the central dopamine pathways. Previous empirical studies suggest a differential effect of acoustic noise in normal children and children with attention-deficit hyperactivity disorder (ADHD). This study investigated the effect of acoustic noise on PPI and if dopamine transmission interacts with acoustic noise effects in a rat ADHD model. The effect of background acoustic noise on acoustic startle response and PPI were measured with a constant prepulse to background noise ratio of 9 dB(A). Spontaneously hypertensive (SH) rats were used as the ADHD model and compared with Wistar and Sprague-Dawley rats. Microdialysis, methylphenidate treatment and 6-OHDA lesions were used to investigate interaction with dopamine transmission. Background noise facilitated PPI differently in SH rats and controls. The prefrontal cortex in SH rats had low basal dopamine concentrations, a high DOPAC/dopamine ratio and blunted dopamine release during PPI testing. Methylphenidate had small, but strain-specific, effects on startle and PPI. Bilateral 6-hydroxydopamine lesions did not alter startle or PPI. Prefrontal dopamine transmission is altered in SH rats during the sensorimotor gating task of PPI of the acoustic startle, indicating increased dopamine reuptake in this ADHD rat model. We propose that noise benefit could be explored as a non-pharmacological alternative for treating neuropsychiatric disorders.
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| 10. |
- Samoudi, Ghazaleh, et al.
(author)
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Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats.
- 2012
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:1
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Journal article (peer-reviewed)abstract
- The vestibular system is connected to spinal, cerebellar and cerebral motor control structures and can be selectively activated with external electrodes. The resulting sensation of disturbed balance can be avoided by using stochastic stimulation patterns. Adding noise to the nervous system sometimes improves function. Small clinical trials suggest that stochastic vestibular stimulation (SVS) may improve symptoms in Parkinson's disease. We have investigated this claim and possible mechanisms using the 6-hydroxydopamine (6-OHDA) hemilesion model of Parkinson's disease.
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