Neuroscience
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Noradrenergic signaling, through the α2A and α2C adrenergic receptors modulates the cognitive and behavioral symptoms of disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. However, it is unknown whether the α2B receptor has any significant role in CNS function. The present study elucidates the potential role of the α2B receptor in CNS function via the discovery and use of the first subtype-selective α2B antagonist (AGN-209419), and behavioral analyses of α-receptor knockout (KO) mice. ⋯ However, α2B KO mice exhibited stereotypy at doses of amphetamine that were only locomotor stimulatory to all other genotypes. Following co-administration of AGN-209419 with low-dose amphetamine in WT mice, stereotypy was observed, mimicking the α2B KO phenotype. These findings suggest that the α2B receptor is involved in CNS behaviors associated with sensorimotor gating and compulsivity, and may be therapeutically relevant for disorders such as schizophrenia, ADHD, post-traumatic stress disorder, addiction, and obsessive compulsive disorder.
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Transcranial direct current stimulation improves isometric time to exhaustion of the knee extensors.
Transcranial direct current stimulation (tDCS) can increase cortical excitability of a targeted brain area, which may affect endurance exercise performance. However, optimal electrode placement for tDCS remains unclear. We tested the effect of two different tDCS electrode montages for improving exercise performance. ⋯ Central and peripheral parameters, and HR and PAIN did not present any differences between conditions after tDCS stimulation (P>0.05). In all conditions maximal voluntary contraction (MVC) significantly decreased after the TTE (P<0.05) while motor-evoked potential area (MEP) increased after TTE (P<0.05). These findings demonstrate that SHOULDER montage is more effective than HEAD montage to improve endurance performance, likely through avoiding the negative effects of the cathode on excitability.
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This study sought to determine the effects of chronic low back pain (LBP) on the cortical evoked potentials, muscle activation, and kinematics of postural responses to perturbations of standing balance. Thirteen subjects with chronic, recurrent, non-specific LBP and 13 subjects without LBP participated. The subjects responded to unpredictably timed postural perturbations while standing on a platform that randomly rotated either "toes up" or "toes down". ⋯ For the subjects with LBP, CoM displacements significantly and positively correlated with knee displacements as well as activity interference and fear scores. The P2 potentials significantly and negatively correlated with CoM displacements as well as activity interference, catastrophizing, and fear scores. These results demonstrate that people with LBP exhibit altered late-phase cortical processing of postural perturbations concomitant with altered kinematic and muscle responses, and these cortical and postural response characteristics correlate with each other as well as with clinical reports of pain-related fears and activity interference.
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The endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. ⋯ Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD) while VDM-11 caused a decline in contents of these molecules. These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking. It can be concluded that elements of the endocannabinoid system, such as the CB1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking.
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Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid's impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. ⋯ Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health.