Suppression Of Hyperactivity Research Articles

Unravelling leptin-sensitive neuronal circuits involved in suppression of hyperactivity in activity based anorexia model

Unravelling leptin-sensitive neuronal circuits involved in suppression of hyperactivity in activity based anorexia model

Beneficial Effects of Cathodal Transcranial Direct Current Stimulation (tDCS) on Cognitive Performance

Transcranial brain stimulation is increasingly used to improve compromised and physiological cognitive functioning. Various forms of transcranial electric stimulation build on the neurophysiological effects of weak currents that are directed to brain areas to induce modulations of cortical activity. The anode-excitatory cathode-inhibitory (AeCi) physiological model of transcranial direct current stimulation (tDCS) is often expected to produce mirrored cognitive effects for stimulations of relevant cortical areas, e.g., prefrontal cortices. However, recent research indicates that cognitive performance can also be improved via cathodal tDCS. Nevertheless, considering that different cortical structures may interact with current flow in varying ways, it is not adequate to reject AeCi entirely, to deduct a different physiological effect from cognitive outcomes, or to assume an inefficiency of cathodal tDCS in modulating higher order cortical functions. By highlighting beneficial outcomes, we present here an alternative view on cognitive enhancements that is consistent with the concept of a predominantly inhibitory effect of cathodal tDCS. Suppression of hyperactivity, dysfunctional network activity, noise filtering, state-dependent activity tuning (homeostatic plasticity), and distant disinhibition are discussed as possible mechanisms of action. Consideration of these aspects may allow for a better understanding of the complex results of tDCS studies on the malleability of cognition and behaviour.

NR2A- and NR2B-NMDA receptors and drebrin within postsynaptic spines of the hippocampus correlate with hunger-evoked exercise

Hunger evokes foraging. This innate response can be quantified as voluntary wheel running following food restriction (FR). Paradoxically, imposing severe FR evokes voluntary FR, as some animals choose to run rather than eat, even during limited periods of food availability. This phenomenon, called activity-based anorexia (ABA), has been used to identify brain changes associated with FR and excessive exercise (EX), two core symptoms of anorexia nervosa (AN), and to explore neurobiological bases of AN vulnerability. Previously, we showed a strong positive correlation between suppression of FR-evoked hyperactivity, i.e., ABA resilience, and levels of extra-synaptic GABA receptors in stratum radiatum (SR) of hippocampal CA1. Here, we tested for the converse: whether animals with enhanced expression of NMDA receptors (NMDARs) exhibit greater levels of FR-evoked hyperactivity, i.e., ABA vulnerability. Four groups of animals were assessed for NMDAR levels at CA1 spines: (1) ABA, in which 4days of FR was combined with wheel access to allow voluntary EX; (2) FR only; (3) EX only; and (4) control (CON) that experienced neither EX nor FR. Electron microscopy revealed that synaptic NR2A-NMDARs and NR2B-NMDARs levels are significantly elevated, relative to CONs'. Individuals' ABA severity, based on weight loss, correlated with synaptic NR2B-NMDAR levels. ABA resilience, quantified as suppression of hyperactivity, correlated strongly with reserve pools of NR2A-NMDARs in spine cytoplasm. NR2A- and NR2B-NMDAR measurements correlated with spinous prevalence of an F-actin binding protein, drebrin, suggesting that drebrin enables insertion of NR2B-NMDAR to and retention of NR2A-NMDARs away from synaptic membranes, together influencing ABA vulnerability.

Antidepressant mechanism of add-on repetitive transcranial magnetic stimulation in medication-resistant depression using cerebral glucose metabolism

Background Add-on repetitive transcranial magnetic stimulation (rTMS) is effective in treating medication-resistant depression (MRD), but little is known about the rTMS antidepressant mechanism and pathophysiology underlying MRD. Methods Twenty MRD patients received 2 weeks of navigated add-on rTMS to the left dorsolateral prefrontal cortex (DLPFC). Treatment response was defined as a ≥ 50% decrease in HDRS after treatment. Cerebral glucose metabolism was measured from all MRD patients twice, before and 3 months after rTMS, and from 20 healthy controls once at baseline. Results At baseline, MRD subjects presented significant hypometabolism at the bilateral DLPFC and anterior cingulum, as well as hypermetabolism at several limbic and subcortical regions compared to the controls. Higher metabolism at the medial PFC and rostral anterior cingulum, and lower metabolism at the limbic structures, including the left parahippocampus and fusiform gyrus, predicted a response to rTMS. After successful rTMS treatment, the abnormally elevated metabolism in the left middle temporal cortex and fusiform gyrus decreased significantly, suggesting a reversal of metabolic imbalances. However, the overall metabolic pattern was still abnormal, even after their depression was under control. In contrast, the non-responders showed a worsening pattern of increased metabolism in the bilateral temporal cortex and fusiform gyrus. Conclusions The antidepressant mechanism of add-on rTMS may be reflected as suppression of hyperactivity in the left temporal cortex and fusiform gyrus, perhaps through enhancing the function of the medial prefrontal cortex and anterior cingulum. The limbic-cortical dysregulation of glucose metabolism might be a trait of an underlying mechanism of MRD.

Dopamine antagonism inhibits anorectic behavior in an animal model for anorexia nervosa

Excessive physical activity is commonly described as symptom of Anorexia Nervosa (AN). Activity-based anorexia (ABA) is considered an animal model for AN. The ABA model mimics severe body weight loss and increased physical activity. Suppression of hyperactivity by olanzapine in anorectic patients as well as in ABA rats suggested a role of dopamine and/or serotonin in this trait. Here, we investigated the effect of a non-selective dopamine antagonist in the ABA model. A dose–response curve of chronic treatment with the non-selective dopaminergic antagonist cis-flupenthixol was determined in the ABA model. Treatment reduced activity levels in both ad libitum fed and food-restricted rats. Treated ABA rats reduced body weight loss and increased food intake. These data support a role for dopamine in anorexia associated hyperactivity. Interestingly, in contrast to leptin treatment, food-anticipatory activity still persists in treated ABA rats.

Food-anticipatory activity in activity-based anorexia: The involvement of dopamine.

Anorexia nervosa (AN) is a severe psychiatric disorder with a high mortality rate. Excessive physical activity and reduced food consumption are commonly described as symptoms of AN. Suppression of hyperactivity by antipsychotics suggest a role of dopamine and serotonin in this trait in AN patients. Activity-based anorexia (ABA) is considered as an animal model for AN. The ABA model consists of scheduled feeding in combination with voluntary wheel running, which results in severe body weight loss and increased physical activity. The hyperactive behavior prior to food access is described as food anticipatory activity. In order to determine the role of dopamine, a dose-response curve of chronic treatment of rats with the non-selective dopaminergic antagonist cis-flupenthixol (ranging from 0.03 to 1.0 mg/day) was determined in the ABA model. Flupenthixol treatment (1.0 mg/day) significantly reduced running wheel activity levels in both ad libitum fed and food-restricted rats. During ABA, flupenthixol-treated rats significantly reduced their body weight loss and increased fat depots, while food intake was not significantly different from vehicle-treated rats. Interestingly, food anticipatory activity still persists in flupenthixol-treated food-restricted rats. These data show that chronic treatment with flupenthixol induces body weight gain in food-restricted rats and reduces running wheel activity levels in ad libitum fed as well as food-restricted rats. We also conclude that blockade of dopamine receptors does not affect food anticipatory activity in ABA rats.