Exploring neural correlates of social dominance: Insights from behavioral, resting- state EEG, and ERP indices.

Numerous studies have explored the concept of social dominance and its implications for leadership within the behavioral and cognitive sciences in recent years. The current study aims to address the gap regarding the neural correlates of social dominance by investigating the associations between psychological measures of social dominance and neural features among a sample of leaders. Thirty healthy male volunteers engaged in a monetary gambling task while their resting-state and task-based electroencephalography data were recorded. The results revealed a positive association between social dominance and resting-state beta oscillations in central electrodes. Furthermore, a negative association was observed between social dominance and task-based reaction time as well as the amplitude of the feedback-related negativity component of the event-related potentials during the gain, but not the loss condition. These findings suggest that social dominance is associated with enhanced reward processing which has implications for social and interpersonal interactions.

Maladaptive plasticity induced by morphine is mediated by hippocampal astrocytic Connexin-43.

AIMS: Drug addiction is an aberrant learning process that involves the recruitment of memory systems. We have previously demonstrated that morphine exposure causes maladaptive synaptic plasticity which involved hippocampal glial cells, especially astrocytes. Morphine addiction has been associated with astrocytic connexin 43 (Cx43), which plays a role in synaptic homeostasis. This study aimed to examine the role of hippocampal astrocytic Cx43 in morphine-induced maladaptive plasticity as a mechanism of addiction. MAIN METHODS: Male rats were injected with morphine (10 mg/kg) subcutaneously every 12 h for nine days to induce dependence. Cx43 was inhibited by TAT-Gap19 (1 µl/1 nmol) microinjection in the CA1 region of the hippocampus 30 min before each morning morphine injection. Field potential recordings were used to assess synaptic plasticity. fEPSP was recorded from the CA1 area following CA3 stimulation. KEY FINDINGS: Electrophysiological results showed that morphine treatment altered baseline synaptic responses. It also appears that morphine treatment augmented long-term potentiation (LTP) compared with the control group. Hippocampal astrocytic Cx43 inhibition, with the TAT-Gap19, undermines these effects of morphine on baseline synaptic responses and LTP. Despite this, long-term depression (LTD) did not differ significantly between the groups. Additionally, in the morphine-receiving group, inhibition of Cx43 significantly reduced the paired-pulse index at an 80-millisecond inter-pulse interval when assessing short-term plasticity. SIGNIFICANCE: The results of this study demonstrated that inhibiting Cx43 reduced synaptic plasticity induced by morphine. It can be concluded that hippocampal astrocytes through Cx43 are involved in morphine-induced metaplasticity.

Machine learning-based classifying of risk-takers and risk-aversive individuals using resting-state EEG data: A pilot feasibility study.

BACKGROUND: Decision-making is vital in interpersonal interactions and a country's economic and political conditions. People, especially managers, have to make decisions in different risky situations. There has been a growing interest in identifying managers' personality traits (i.e., risk-taking or risk-averse) in recent years. Although there are findings of signal decision-making and brain activity, the implementation of an intelligent brain-based technique to predict risk-averse and risk-taking managers is still in doubt. METHODS: This study proposes an electroencephalogram (EEG)-based intelligent system to distinguish risk-taking managers from risk-averse ones by recording the EEG signals from 30 managers. In particular, wavelet transform, a time-frequency domain analysis method, was used on resting-state EEG data to extract statistical features. Then, a two-step statistical wrapper algorithm was used to select the appropriate features. The support vector machine classifier, a supervised learning method, was used to classify two groups of managers using chosen features. RESULTS: Intersubject predictive performance could classify two groups of managers with 74.42% accuracy, 76.16% sensitivity, 72.32% specificity, and 75% F1-measure, indicating that machine learning (ML) models can distinguish between risk-taking and risk-averse managers using the features extracted from the alpha frequency band in 10 s analysis window size. CONCLUSIONS: The findings of this study demonstrate the potential of using intelligent (ML-based) systems in distinguish between risk-taking and risk-averse managers using biological signals.

Feedback-related negativity in perfectionists: An index of performance outcome evaluation.

It has been suggested that maladaptive perfectionists are more prone to concern over their performance outcomes than adaptive perfectionists. Performance outcome evaluation is reflected in the amplitude of feedback-related negativity (FRN) in brain electroencephalography (EEG). Hence, the amplitude of the FRN after receiving unfavorable feedback indicating a negative performance outcome may reflect personality characteristics. In other words, EEG could be a better marker of personality characteristics than self-report measures. However, the FRN component has not yet been investigated between different types of perfectionists. In the present study, group differences in the FRN were examined between two groups of adaptive and maladaptive perfectionists and a group of non-perfectionists during a monetary gambling task. We observed a larger FRN amplitude for adaptive perfectionists than for maladaptive perfectionists. This finding is consistent with previous reports that reward prediction error is reflected in the amplitude of the FRN. This difference in FRN could be interpreted as the pessimistic outcome expectation biases in maladaptive perfectionists.

Effects of social hierarchy on innate fear­induced panic responses.

Studies have previously demonstrated a relationship between social status and anxiety disorders such as panic disorder. Repeated episodes of panic attacks do not occur in combination with an actual fear stimulus or stressor. However, social ranking modulates the perception of the social signals of a threat or stressor. The hypothalamic nuclei are well­known for their role in the elaboration of fear­induced reactions. The dorsomedial hypothalamus (DMH) and the ventromedial hypothalamic (VMH) nuclei are hypothalamic subnuclei involved in the processing of threatening stimuli­evoked aversive response and innate fear development. These structures are also located in the medial amygdala­hypothalamus­brainstem circuit that modulates innate fear­induced defensive behaviors. This work aimed to investigate the relationship between social hierarchy and innate fear­induced panic­like responses in male rats. In our study, the dominance tube test was used to determine the social hierarchy. Then, DMH/VMH nuclei were unilaterally implanted with a guide cannula. After intra­DMH/VMH injection of bicuculline (GABAA receptor antagonist), both innate fear induction and differences in dominant/subordinate rats were evaluated by the open field test. Intra­DMH/VMH bicuculline increased the frequency of defensive immobility, forward escape movements, and crossing behaviors, as well as the duration of defensive immobility and forward escape movements in dominant rats. Subordinate rats showed a higher frequency of defensive attention, defensive immobility, and crossing than dominant rats. Additionally, dominant rats demonstrated a lower duration of defensive attention and defensive immobility than subordinate rats. Dominant rats seemed to adopt a form of innate­fear characterized by increased proactivity with the environment. In contrast, subordinate rats exhibited a reactive form of innate­fear characterized by passivity and freezing.

Ecballium elaterium attenuates neuroinflammation in an animal model of Alzheimer's disease through modulation of nuclear factor κB pathway.

OBJECTIVE: Sustained inflammation, which could be promoted by Aß aggregation and tau hyperphosphorylation, is a critical player in Alzheimer's disease (AD) pathogenesis. In the first phase, this study was designed to evaluate the anti-inflammatory properties of Ecballium elaterium (EE), as a Mediterranean therapeutic plant, and its effects on biochemical and behavioral signs of nucleus basalis of Meynert lesioned (NBML) rats, as an approved model of AD. In the second phase, we investigated the effect of EE on nuclear factor (NF)-κB pathway which is responsible for encoding proteins involved in the inflammatory cascade. MATERIALS AND METHODS: Animals were divided randomly into four groups as following: control, NBML rats (AD), AD rats that were treated by high- and low-dose EE. Prostaglandins (PGs) levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Cyclooxygenase-2 (COX-2) and acetylcholinesterase (AChE) levels were assessed by fluorometric kit and Elman method, respectively. Behavioral signs were evaluated by Morris Water Maze (MWM) test and inflammatory proteins content was analyzed by immunoblotting method. RESULTS: According to the results, treatment of NBML rats with EE fruit juice reduced PGs and cytokines more than 2-fold in comparison with AD rats through inhibition of COX-2 enzyme. Attenuation of inflammatory response in NBML rats was accompanied by reduced AChE activity (about 3-fold) and improved learning ability. Interestingly, EE reduced NF-κB expression for about 3-fold which resulted in a more than 10-fold increase in IκBα/P-IκBα ratio. CONCLUSION: Our results confirmed the TNF-α/cytokines/NF-κB/COX-2 pathway involves as the main inflammatory response in NBML rats. We also provided biochemical and behavioral evidence which introduces EE as an anti-inflammatory adjuvant to improve pathophysiological signs in patients suffering from AD and related dementia.

Involvement of Hippocampal Astrocytic Connexin-43 in Morphine dependence.

Repeated exposure to drugs of abuse can lead to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters. Such alterations in neurotransmission modify synaptic plasticity which causes addictive-like behaviors. Our previous study shed light on the involvement of glial cells in morphine-induced behavioral responses. It has been shown that glial cells play an indispensable role in synaptic transmission through the release of gliotransmitter into and uptake of neurotransmitters from the synaptic cleft. Connexin-43 (Cx43), the dominant Cx protein in astrocytes, is the main component of astrocytic gap junctions and hemichannels. It has a critical role in synaptic efficacy through setting the amount of presynaptic gliotransmitter release in physiological conditions. It is probable that addictive substances affecting gliotransmitters release through the alteration of Cx43 function. In this study, we examined the role of the hippocampal-specific astrocytic connexin (Cx43) in morphine-induced behavioral responses. Male rats received subcutaneous (s.c.) morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. The animals received microinjection of TAT-Gap19 (inhibitor of Cx43) into the CA1 region before each morning morphine administration. The animals were assessed for morphine dependence by monitoring naloxone hydrochloride precipitated withdrawal somatic signs. Results showed that animals receiving TAT-Gap19 before morphine injection demonstrated a significant reduction in several signs of morphine withdrawal such as Activity, Freezing, Chewing, Ptosis, Defecation, Teeth chattering, Writhing, Penis- licking, Head tremor, Scratching, Sniffing, Rearing, and Diarrhea (One way ANOVA, P < 0.001; P < 0.01; P < 0.05). Our findings suggest that hippocampal Cx43 may be involved in morphine-induced behavioral responses. Therefore, gliotransmitter release by astrocytes seems to be a mechanism which is engaged in addictive-like behaviors.

Closed-loop Modulation of the Self-regulating Brain: A Review on Approaches, Emerging Paradigms, and Experimental Designs.

Closed-loop approaches, setups, and experimental designs have been applied within the field of neuroscience to enhance the understanding of basic neurophysiology principles (closed-loop neuroscience; CLNS) and to develop improved procedures for modulating brain circuits and networks for clinical purposes (closed-loop neuromodulation; CLNM). The contents of this review are thus arranged into the following sections. First, we describe basic research findings that have been made using CLNS. Next, we provide an overview of the application, rationale, and therapeutic aspects of CLNM for clinical purposes. Finally, we summarize methodological concerns and critics in clinical practice of neurofeedback and novel applications of closed-loop perspective and techniques to improve and optimize its experiments. Moreover, we outline the theoretical explanations and experimental ideas to test animal models of neurofeedback and discuss technical issues and challenges associated with implementing closed-loop systems. We hope this review is helpful for both basic neuroscientists and clinical/ translationally-oriented scientists interested in applying closed-loop methods to improve mental health and well-being.

Facial Emotion Recognition Predicts Alexithymia Using Machine Learning.

OBJECTIVE: Alexithymia, as a fundamental notion in the diagnosis of psychiatric disorders, is characterized by deficits in emotional processing and, consequently, difficulties in emotion recognition. Traditional tools for assessing alexithymia, which include interviews and self-report measures, have led to inconsistent results due to some limitations as insufficient insight. Therefore, the purpose of the present study was to propose a new screening tool that utilizes machine learning models based on the scores of facial emotion recognition task. METHOD: In a cross-sectional study, 55 students of the University of Tabriz were selected based on the inclusion and exclusion criteria and their scores in the Toronto Alexithymia Scale (TAS-20). Then, they completed the somatization subscale of Symptom Checklist-90 Revised (SCL-90-R), Beck Anxiety Inventory (BAI) and Beck Depression Inventory-II (BDI-II), and the facial emotion recognition (FER) task. Afterwards, support vector machine (SVM) and feedforward neural network (FNN) classifiers were implemented using K-fold cross validation to predict alexithymia, and the model performance was assessed with the area under the curve (AUC), accuracy, sensitivity, specificity, and F1-measure. RESULTS: The models yielded an accuracy range of 72.7-81.8% after feature selection and optimization. Our results suggested that ML models were able to accurately distinguish alexithymia and determine the most informative items for predicting alexithymia. CONCLUSION: Our results show that machine learning models using FER task, SCL-90-R, BDI-II, and BAI could successfully diagnose alexithymia and also represent the most influential factors of predicting it and can be used as a clinical instrument to help clinicians in diagnosis process and earlier detection of the disorder.

The role of hippocampal glial glutamate transporter (GLT-1) in morphine-induced behavioral responses.

Opioid abuse modifies synaptic plasticity, which leads to behavioral changes, such as morphine dependence, but the mechanism remains poorly understood. Glial cells play an important role in the modulation of synaptic plasticity and are involved in addictive-like behaviors. The indisputable role of glutamate in opiate addiction has been shown. Astrocytes, a type of glial cells, which are integral functional elements of synapses, modulate the concentration of glutamate in the synaptic space. One of the most important mechanisms for glutamate concentration regulation is its uptake from the synaptic cleft. In this study, we evaluated the role of hippocampal glial glutamate transporter (GLT-1) in morphine dependence. Male rats received subcutaneous (s.c.) morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. In order to activate GLT-1, animals received an intrahippocampal injection of ceftriaxone (0.5 mmol/0.5 µl) in the CA1 region of the hippocampus, 30 min before each morphine administration. Rats were assessed for morphine dependence by monitoring naloxone hydrochloride-induced morphine withdrawal. Our results showed that hippocampal microinjection of ceftriaxone, as an activator of GLT-1, reduced some signs of morphine withdrawal, such as activity, diarrhea, head tremor, freezing, and ptosis. It seems that hippocampal GLT-1 can be affected by chronic morphine administration and involved in morphine dependence. Therefore, its activation may reduce morphine side effects by reducing hippocampal glutamate.

Non-selective COX inhibitors impair memory formation and short-term but not long-term synaptic plasticity.

Cyclooxygenase (COX) plays a critical role in synaptic plasticity. Therefore, long-term administration of acetylsalicylic acid (ASA) and its main metabolite, salicylate, as a COX inhibitor may impair synaptic plasticity and subsequently memory formation. Although different studies have tried to explain the effects of ASA and sodium salicylate (SS) on learning and memory, the results are contradictory and the mechanisms are not exactly known. The present study was designed to investigate the effects of long-term low-dose (equivalent to prophylactic dose) and short-term high-dose (equivalent to analgesic dose) administration of ASA and SS respectively, on spatial learning and memory and hippocampal synaptic plasticity. Animals were treated with a low dose of ASA (2 mg/ml solvated in drinking water, 6 weeks) or a high dose of SS, a metabolite of ASA, (300 mg/kg, 3 days, twice-daily, i.p). Spatial memory and synaptic plasticity were assessed by water maze performance and in vivo field potential recording from CA1, respectively. Animals treated with ASA but not SS showed a significant increase in escape latency and distance moved. Furthermore, in the probe test, animals treated with both drugs spent less time in the target quadrant zone. The paired-pulse ratio (PPR) at 20-ms inter-pulse intervals (IPI) as an index of short-term plasticity in both treated groups was significantly higher than of the control group. Interestingly, none of the administered drugs affected long-term potentiation (LTP). These data suggested that long-term inhibition of COX disrupted memory acquisition and retrieval. Interestingly, cognitive impairments happened along with short-term but not long-term synaptic plasticity disturbance.

Ameliorating Effects of Dorema ammoniacum on PTZ-Induced Seizures and Epileptiform Brain Activity in Rats.

The objective of the current study was to investigate the anti-epileptogenic and anticonvulsant effects of Dorema ammoniacum gum, which is used in Iranian traditional medicine for the treatment of seizures. Animals received pentylenetetrazol (IP, 30 mg/kg/48 h) for inducing seizures. Five different seizure stages were evaluated for 20 min and parameters including maximum seizure stage, the latency to the onset of stage 4, stage 4 duration, and seizure duration were measured. D. ammoniacum (50 and 100 mg/kg) or its vehicle was administered 30 min before or after pentylenetetrazol injection in different groups. In addition, the effective dose of D. ammoniacum (100 mg/kg) on different seizure stages was compared with the common antiseizure drug phenobarbital. In another set of experiments, we investigated the effective dose of D. ammoniacum on fully kindled animals in which an interictal electroencephalogram was recorded by superficial electrodes placed on the skull. The results showed that D. ammoniacum administration, before and after pentylenetetrazol injections, significantly decreased seizure stage, seizure duration, stage 4 duration, and 1/stage 4 latency. The anti-epileptogenic effect of D. ammoniacum was about 50 to 60% of phenobarbital. In addition, D. ammoniacum significantly decreased seizure stage, seizure duration, stage 4 duration, and 1/stage 4 latency when administered to fully kindled animals but had no effect on the power of EEG sub-bands. These results indicate that D. ammoniacum has anti-epileptogenic and anticonvulsant effects in a chemical kindling model of seizures.

Effects of Delphinidin on Pathophysiological Signs of Nucleus Basalis of Meynert Lesioned Rats as Animal Model of Alzheimer Disease.

Alzheimer's disease (AD) is an advanced neurodegenerative disorder greatly accompanied by cognitive deficits, oxidative stress, inflammation, amyloid plaques deposition, and acetylcholinesterase (AChE) hyper-activation. Growing evidence suggests natural compounds with antioxidant and anti-inflammatory features improve pathophysiological signs of AD. The present study was designed to investigate the effects of Delphinidin (25, 50 mg/kg) as an anthocyanidin on spatial memory impairment and AD hallmarks such as hippocampal AChE activity, amyloid plaques deposition, oxidative stress and expression of amyloid precursor protein (APP), AChE, and amyloid beta (Aß) proteins in nucleus basalis of Meynert (NBM) lesioned rats as the most prevalent animal model of AD. Interestingly, Delphinidin-treated animals showed a significant decrease in escape latency and distance moved. Furthermore, in probe test, NBM lesioned rats treated with both doses of Delphinidin spent more time in the target quadrant zone in Morris water maze task. It could also interact with catalytic site of AChE enzyme and inhibits acetylcholine hydrolysis in in vitro and in vivo conditions. In addition, Delphinidin could scavenge additional produced reactive oxygen molecules dose dependently. Our immunoblotting analysis confirmed high dose of Delphinidin reduced AChE, APP and Aß contents in AD model. Staining of hippocampus tissue revealed that Delphinidin treatment decreased amyloid plaques formation in NBM lesion rats. It seems that Delphinidin is a plate-like molecule intercalated between ß-plated sheets related to Aß molecules and inhibited amyloid fibril formation. Altogether, Delphinidin and Delphinidin-rich fruits could be suggested as a therapeutic adjuvant in AD and other related cognitive disorders.

Impaired cerebellar plasticity and eye-blink conditioning in calpain-1 knock-out mice.

Calpain-1 and calpain-2 are involved in the regulation of several signaling pathways and neuronal functions in the brain. Our recent studies indicate that calpain-1 is required for hippocampal synaptic plasticity, including long-term depression (LTD) and long-term potentiation (LTP) in field CA1. However, little is known regarding the contributions of calpain-1 to cerebellar synaptic plasticity. Low frequency stimulation (LFS, 5 Hz, 5 min)-induced LTP at parallel fibers to Purkinje cell synapses was markedly impaired in cerebellar slices from calpain-1 knock-out (KO) mice. Application of a selective calpain-2 inhibitor enhanced LFS-induced LTP in both wild-type (WT) and calpain-1 KO mice. Three protocols were used to induce LTD at these synapses: LFS (1 Hz, 15 min), perfusion with high potassium and glutamate (K-Glu) or dihydroxyphenylglycine (DHPG), a mGluR1 agonist. All three forms of LTD were impaired in calpain-1 KO mice. DHPG application stimulated calpain-1 but not calpain-2 in cerebellar slices, and DHPG-induced LTD impairment was reversed by application of a protein phosphatase 2A (PP2A) inhibitor, okadaic acid. As in hippocampus, BDNF induced calpain-1 activation and PH domain and Leucine-rich repeat Protein Phosphatase 1/suprachiasmatic nucleus oscillatory protein (PHLPP1/SCOP) degradation followed by extracellular signal-regulated kinase (ERK) activation, as well as calpain-2 activation leading to degradation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in cerebellar slices. The role of calpain-1 in associative learning was evaluated in the delay eyeblink conditioning (EBC). Calpain-1 KO mice exhibited significant learning impairment in EBC during the first 2 days of acquisition training. However, after 5 days of training, the percentage of conditioned responses (CRs) between calpain-1 KO and WT mice was identical. Both calpain-1 KO and WT mice exhibited typical extinction patterns. Our results indicate that calpain-1 plays critical roles in multiple forms of synaptic plasticity and associative learning in both hippocampus and cerebellum.

Ca2+ Channels Involvement in Low-Frequency Stimulation-Mediated Suppression of Intrinsic Excitability of Hippocampal CA1 Pyramidal Cells in a Rat Amygdala Kindling Model.

Low-frequency stimulation has demonstrated promising seizure suppression in animal models of epilepsy, while the mechanism of the effect is still debated. Changes in intrinsic properties have been recognized as a prominent pathophysiologically relevant feature of numerous neurological disorders including epilepsy. Here, it was evaluated whether LFS can preserve the intrinsic neuronal electrophysiological properties in a rat model of epilepsy, focusing on the possible involvement of voltage-gated Ca2+ channels. The amygdala kindling model was induced by 3 s monophasic square wave pulses (50 Hz, 1 ms duration, 12times/day at 5 min intervals). Both LFS alone and kindled plus LFS (KLFS) groups received four packages of LFS (each consisting of 200 monophasic square pulses, 0.1 ms pulse duration at 1 Hz with the after discharge threshold intensity), which in KLFS rats was applied immediately after kindling induction. Whole-cell patch-clamp recordings were made in the presence of fast synaptic blockers 24 h after the last kindling stimulations or following kindling stimulations plus LFS application. In the KLFS group, both the rebound excitation and kindling-induced intrinsic hyperexcitability were decreased, associated with a regular intrinsic firing as indicated by a lower coefficient of variation. The amplitude of afterdepolarization (ADP) and its area under the curve were both decreased in the KLFS group compared to the kindled group. LFS prevented the increasing effect of kindling on Ca2+ currents in the KLFS group. Findings provided evidence for a novel form of epileptiform activity suppression by LFS in the presence of synaptic blockade possibly by decreasing Ca2+ currents.

Combination Effects of Forced Mild Exercise and GABAB Receptor Agonist on Spatial Learning, Memory, and Motor Activity in Striatum Lesion Rats.

Basal ganglia (BG) lesions cause impairments of different mammalian's movement and cognition behaviors. Motor circuit impairment has a dominant role in the movement disorders. An inhibitory factor in BG is GABA neurotransmitter, which is released from striatum. Lesions in GABAergic neurons could trigger movement and cognition disorders. Previous evidence showed that GABAB receptor agonist (Baclofen) administration in human improves movement disorders and exercise can improve neurodegenerative and cognitive decline; however, the effects of both Baclofen and mild forced treadmill exercise on movement disorders are not well known. The main objective of this study is to investigate the combined effects of mild forced treadmill exercise and microinjection of Baclofen in the internal Globus Pallidus on striatum lesion-induced impairments of spatial learning and motor activity. We used Morris water maze and open filed tests for studying spatial learning, and motor activity, respectively. Results showed that mild exercise and Baclofen microinjection could not lonely affect the spatial learning, and motor activity impairments while the combination of them could alleviate spatial learning, and motor activity impairments in striatum-lesion animals. Our results suggest that striatum lesion-induced memory and motor activity impairments can improve with combination interaction of GABAB receptor agonist and exercise training.

Methamphetamine neurotoxicity, microglia, and neuroinflammation.

Methamphetamine (METH) is an illicit psychostimulant that is subject to abuse worldwide. While the modulatory effects of METH on dopamine neurotransmission and its neurotoxicity in the central nervous system are well studied, METH's effects on modulating microglial neuroimmune functions and on eliciting neuroinflammation to affect dopaminergic neurotoxicity has attracted considerable attention in recent years. The current review illuminates METH-induced neurotoxicity from a neuropathological perspective by summarizing studies reporting microglial activation after METH administration in rodents. Assessing microglial reactivity in terms of the cells' morphology and immunophenotype offers an opportunity for comprehensive and objective assessment of the severity and nature of METH-induced neuronal perturbations in the CNS and can thus contribute to a better understanding of the nature of METH toxicity. We reach the conclusion here that the intensity of microglial activation reported in the majority of animal models after METH administration is quite modest, indicating that the extent of dopaminergic neuron damage directly caused by this neurotoxicant is relatively minor. Our conclusion stands in contrast to claims of excessive and detrimental neuroinflammation believed to contribute and exacerbate METH neurotoxicity. Thus, our analysis of published studies does not support the idea that suppression of microglial activity with anti-inflammatory agents could yield beneficial effects in terms of treating addiction disorders.

Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels.

Aggregated amyloid beta (Aß) peptides are believed to play a decisive role in the pathology of Alzheimer's disease (AD). Previous evidence suggested that exercise contributes to the improvement of cognitive decline and slows down pathogenesis of AD; however, the exact mechanisms for this have not been fully understood. Here, we evaluated the effect of a 4-week moderate treadmill exercise on spatial memory via central and peripheral Aß clearance mechanisms following developed AD-like neuropathology induced by intra-hippocampal Aß1-42 injection in male Wistar rats. We found Aß1-42-treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aß1-42 (sAß1-42), decreased mRNA and protein expression of neprilysin (NEP), insulin degrading enzyme (IDE) and low-density lipoprotein receptor-related protein-1 (LRP-1) in the hippocampus. Aß1-42-treated animals also exhibited a higher level of sAß1-42 and a lower level of soluble LRP-1 (sLRP-1) in plasma, as well as a decreased level of LRP-1 mRNA and protein content in the liver. However, exercise training improved the spatial learning and memory deficits, reduced both plaque load and sAß1-42 levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aß1-42-treated animals. Aß1-42-treated animals subjected to treadmill exercise also revealed decreased levels of sAß1-42 and increased levels of sLRP-1 in plasma, as well as increased levels of LRP-1 mRNA and protein in the liver. In conclusion, our findings suggest that exercise-induced improvement in both of central and peripheral Aß clearance are likely involved in ameliorating spatial learning and memory deficits in an animal model of AD. Future studies need to determine their relative contribution.

Glial cells modulate hippocampal synaptic plasticity in morphine dependent rats.

Drugs of abuse mediate adaptive mechanisms leading to alterations in the synaptic plasticity that has been shown to underlie addictive behaviors. Glial cells play a critical role in modulation of synaptic strength and are potentially involved in drug addiction. Chronic administration of morphine has been shown to increase glial cell activation; therefore, it is possible that altered neuroplasticity induced by drugs of abuse is in part mediated by the activity of glial cells. We investigated the effect of hippocampal glial inhibition on synaptic plasticity in morphine treated rats. The fluorocitrate (an inhibitor of glial cells) was microinjected into the CA1 area before morphine injection. The rats received subcutaneous (s.c.) injections of morphine sulfate (10 mg/kg) every 12 h for 9 days. Field excitatory postsynaptic potentials (fEPSP) were recorded from the stratum radiatum of the CA1 area following Schaffer collateral stimulation. Our results indicated that morphine treatment increases long-term potentiation (LTP) and inhibition of glial cells prevents morphine-induced LTP enhancement. Morphine exposed rats exhibited a resistance to LTD induction, whereas, pretreatment with fluorocitrate reduced this resistance. Glial inhibition did not affect LTP and LTD in the untreated animals. The paired pulse ratio (PPR) in inter stimulus intervals (ISI) of 80 ms in the morphine treated group was significantly higher than the control group, while glial inhibition significantly decreased the PPR in morphine treated rats. Our results suggest that morphine exposure modulates hippocampal short- and long-term synaptic plasticity and these alterations in neuronal activity are in part due to glial activity.