Dopaminergic reward system: a short integrative review

Memory is an essential element to adaptive behavior since it allows consolidation of past experience guiding the subject to consider them in future experiences. Among the endogenous molecules that participate in the consolidation of memory, including the drug-seeking reward, considered as a form of learning, is dopamine. This neurotransmitter modulates the activity of specific brain nucleus such as nuclei accumbens, putamen, ventral tegmental area (VTA), among others and synchronizes the activity of these nuclei to establish the neurobiological mechanism to set the hedonic element of learning. We review the experimental evidence that highlights the activity of different brain nuclei modulating the mechanisms whereby dopamine biases memory towards events that are of motivational significance

Administration of URB597, Oleoylethanolamide or Palmitoylethanolamide Increases Waking and Dopamine in Rats

-acylethanolamines or acylethanolamides. The hydrolysis of OEA and PEA is catalyzed by the fatty acid amide hydrolase (FAAH). A number of FAAH inhibitors that increase the levels of OEA and PEA in the brain have been developed, including URB597. In the present report, we examined whether URB597, OEA or PEA injected into wake-related brain areas, such as lateral hypothalamus (LH) or dorsal raphe nuclei (DRN) would promote wakefulness (W) in rats.Male Wistar rats (250–300 g) were implanted for sleep studies with electrodes to record the electroencephalogram and electromyogram as well as a cannulae aimed either into LH or into DRN. Sleep stages were scored to determine W, slow wave sleep (SWS) and rapid eye movement sleep (REMS). Power spectra bands underly neurophysiological mechanisms of the sleep-wake cycle and provide information about quality rather than quantity of sleep, thus fast Fourier transformation analysis was collected after the pharmacological trials for alpha (for W; α = 8–12 Hz), delta (for SWS; δ = 0.5–4.0 Hz) and theta (for REMS; θ = 6.0–12.0 Hz). Finally, microdialysis samples were collected from a cannula placed into the nucleus accumbens (AcbC) and the levels of dopamine (DA) were determined by HPLC means after the injection of URB597, OEA or PEA. We found that microinjection of compounds (10, 20, 30 µg/1 µL; each) into LH or DRN during the lights-on period increased W and decreased SWS as well as REMS and enhanced DA extracellular levels.URB597, OEA or PEA promoted waking and enhanced DA if injected into LH or DRN. The wake-promoting effects of these compounds could be linked with the enhancement in levels of DA and indirectly mediated by anandamide

Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB1 and CB2), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep–wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N-arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents

Detrimental role of prolonged sleep deprivation on adult neurogenesis

Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis

Sleep Deprivation and Oxidative Stress in Animal Models: A Systematic Review

Because the function and mechanisms of sleep are partially clear, here we applied a meta-analysis to address the issue whether sleep function includes antioxidative properties in mice and rats. Given the expansion of the knowledge in the sleep field, it is indeed ambitious to describe all mammals, or other animals, in which sleep shows an antioxidant function. However, in this paper we reviewed the current understanding from basic studies in two species to drive the hypothesis that sleep is a dynamic-resting state with antioxidative properties. We performed a systematic review of articles cited in Medline, Scopus, and Web of Science until March 2015 using the following search terms: Sleep or sleep deprivation and oxidative stress, lipid peroxidation, glutathione, nitric oxide, catalase or superoxide dismutase. We found a total of 266 studies. After inclusion and exclusion criteria, 44 articles were included, which are presented and discussed in this study. The complex relationship between sleep duration and oxidative stress is discussed. Further studies should consider molecular and genetic approaches to determine whether disrupted sleep promotes oxidative stress

Histone Methylation/Demethylation Inhibition Modulates Sleep

Histone methylation/demethylation plays an important modulatory role in chromatin restructuring, RNA transcription and is essential for controlling a plethora of biological processes. Due to many human diseases have been related to histone methylation/demethylation, several compounds such as 3-deazaneplanocin A (DZNep) or 3-((6-(4,5-Dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoic acid; N-[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-4-pyrimidinyl]-b-Alanine (GSK-J1), have been designed to inhibit histone methylase or suppress histone demethylase, respectively. In the present study, we investigated the effects on the sleep-wake cycle and sleep-related neurochemical levels after systemic injections of DZNep or GSK-J1 given during the light or dark phase in rats. DZNep dose-dependently (0.1, 1.0, or 10 mg/kg, i.p.) prolonged wakefulness (W) duration while decreased slow wave sleep (SWS) and rapid eye movement sleep (REMS) time spent during the lights-on period with no changes observed in dark phase. In opposite direction, GSK-J1 (0.1, 1.0, or 10 mg/kg, i.p.) injected at the beginning of the lights-on period induced no statistical changes in W, SWS, or REMS whereas if administered at darkness, we found a diminution in W and an enhancement in SWS and REMS. Finally, brain microdialysis experiments in freely moving animals were used to evaluate the effects of DZNep or GSK-J1 treatments on contents of sleep-related neurochemicals. The results showed that DZNep boosted extracellular levels of dopamine, norepinephrine, epinephrine, serotonin, adenosine, and acetylcholine if injected at the beginning of the lights-on period whereas GSK-J1 exerted similar outcomes but when administered at darkness. In summary, DZNep and GSK-J1 may control the sleep-wake cycle and sleep-related neurochemicals through histone methylation/demethylation activity

Functional coupling of sensorimotor and associative areas during a catching ball task: a qEEG coherence study

<p>Abstract</p> <p>Background</p> <p>Catching an object is a complex movement that involves not only programming but also effective motor coordination. Such behavior is related to the activation and recruitment of cortical regions that participates in the sensorimotor integration process. This study aimed to elucidate the cortical mechanisms involved in anticipatory actions when performing a task of catching an object in free fall.</p> <p>Methods</p> <p>Quantitative electroencephalography (qEEG) was recorded using a 20-channel EEG system in 20 healthy right-handed participants performed the catching ball task. We used the EEG coherence analysis to investigate subdivisions of alpha (8-12 Hz) and beta (12-30 Hz) bands, which are related to cognitive processing and sensory-motor integration.</p> <p>Results</p> <p>Notwithstanding, we found the main effects for the factor block; for alpha-1, coherence decreased from the first to sixth block, and the opposite effect occurred for alpha-2 and beta-2, with coherence increasing along the blocks.</p> <p>Conclusion</p> <p>It was concluded that to perform successfully our task, which involved anticipatory processes (i.e. feedback mechanisms), subjects exhibited a great involvement of sensory-motor and associative areas, possibly due to organization of information to process visuospatial parameters and further catch the falling object.</p

Remodelado adverso del ventrículo derecho en pacientes obstétricas graves con COVID-19

Introduction: COVID-19 has led to an increased incidence of right ventricular remodeling in severe obstetric patients.Objective: To identify the diagnostic elements that influenced the occurrence of right ventricular remodeling in severe obstetric patients with COVID-19.Methods: A descriptive, cross-sectional, single-center study was performed in 53 severe obstetric patients with COVID-19.Results: The most significant average echocardiographic values were TAPSE (15.4mm), right ventricular end-diastolic diameter (31.3mm) and RV/LV ratio (0.75). An increase in troponins (39.5 ng/L), CPK (338.4 U/L) and CK-MB (51.3 U/L) was observed on admission to the intensive care units, and greater ventricular dilatation and dysfunction were observed in pregnant women with high dímero D (84.6% and 76.9% respectively). AHT (32.07%) was the predominant obstetric risk factor, while patients with bronchial asthma (77.7%) and obesity (69.2%) presented greater dilatation and ventricular dysfunction, respectively. LV ejection fraction constituted the only factor associated with patient survival (p = 0.01).Conclusions: In severe obstetric patients due to COVID-19 decreased TAPSE values and RV dilatation were the main echocardiographic features found. In addition, there was a considerable increase in troponin, CPK and CK-MB values. Greater right ventricular dilatation and dysfunction were recorded in asthmatic and obese women, respectively, with elevated D-dimer values. LV ejection fraction was the only independent factor related to survival in these patients.Introducción: La COVID-19 ha provocado una mayor incidencia de la remodelación ventricular derecha en pacientes obstétricas graves.Objetivo: Identificar los elementos diagnósticos que incidieron en la aparición de la remodelación ventricular derecha en pacientes obstétricas graves por COVID-19.Métodos: Se realizó un estudio descriptivo, transversal, unicéntrico con 53 pacientes obstétricas graves por COVID-19.Resultados: La media más significativa entre los valores ecocardiográficos lo constituyeron el TAPSE (15,4 mm), el diámetro telediastólico del ventrículo derecho (31,3 mm) y la relación VD/ VI (0,75). Se apreció un incremento de las troponinas (39,5 ng/L), CPK (338,4 U/ L) y CK-MB (51,3 U/L), al ingresar en las salas de terapia intensiva y se observó una mayor dilatación y disfunción ventricular en las gestantes con dímero D altos (84,6 % y 76,9 % respectivamente). La HTA (32,07 %) fue el factor de riesgo obstétrico predominante; así como las pacientes con asma bronquial (77,7 %) y obesidad (69,2 %) presentaron una mayor dilatación y disfunción ventricular respectivamente. La fracción de eyección del VI constituyó el único factor asociado a la supervivencia de las pacientes (p = 0,01).Conclusiones: En las pacientes obstétricas graves por COVID-19 los valores de TAPSE disminuido y la dilatación del VD fueron las principales características ecocardiográficas encontradas; además, hubo un aumento considerable de los valores de las troponinas, CPK y CK-MB. Se registró una mayor dilatación y disfunción ventricular derecha en las mujeres asmáticas y obesas, respectivamente, con valores de dímero D elevados. La fracción de eyección del VI fue el único factor independiente relacionado con la supervivencia en estas pacientes

Effects of Aerobic Exercise on Anxiety Symptoms and Cortical Activity in Patients with Panic Disorder: A Pilot Study

Background: The effects of the aerobic exercise on anxiety symptoms in patients with Panic Disorder (PD) remain unclear. Thus, the investigation of possible changes in EEG frontal asymmetry could contribute to understand the relationship among exercise, brain and anxiety. Objective: To investigate the acute effects of aerobic exercise on the symptoms of anxiety and the chronic effects of aerobic exercise on severity and symptoms related to PD, besides the changes in EEG frontal asymmetry. Methods: Ten PD patients were divided into two groups, Exercise Group (EG; n=5) and Control Group (CG; n=5), in a randomized allocation. At baseline and post-intervention, they submitted the psychological evaluation through Panic Disorder Severity Scale (PDSS), Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), EEG frontal asymmetry, and maximal oxygen consumption (VO2max). On the second visit, the patients of EG being submitted to the aerobic exercise (treadmill, 25 minutes, and 50-55% of heart rate reserve) and the CG remained seated for the same period of time. Both groups submitted a psychological evaluation with Subjective Units of Distress Scale (SUDS) at baseline, immediately after (Post-0), and after 10 minutes of the rest pause (Post-10). The patients performed 12 sessions of aerobic exercise with 48-72 hours of interval between sessions. Results: In EG, SUDS increased immediately after exercise practice and showed chronic decrease in BAI and BDI-II as well as increased in VO2max (Post-intervention). Conclusion: Aerobic exercise can promote increase in anxiety acutely and regular aerobic exercise promotes reduction in anxiety levels.Eduardo Lattari acknowledges the financial support of the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Peer Reviewe