Increased Motor Activity Research Articles

Cannabidiol regulates behavioural alterations and gene expression changes induced by spontaneous cannabinoid withdrawal.

Cannabidiol (CBD) represents a promising therapeutic tool for treating cannabis use disorder (CUD). This study aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous cannabinoid withdrawal. Spontaneous cannabinoid withdrawal was evaluated 12h after cessation of CP-55,940 treatment (0.5mg·kg-1 every 12h, i.p.; 7days) in C57BL/6J mice. The effects of CBD (5, 10 and 20mg·kg-1 , i.p.) on withdrawal-related behavioural signs were evaluated by measuring motor activity, somatic signs and anxiety-like behaviour. Furthermore, gene expression changes in TH in the ventral tegmental area, and in the opioid μ receptor (Oprm1), cannabinoid CB1 receptor (Cnr1) and CB2 receptor (Cnr2) in the nucleus accumbens, were also evaluated using the real-time PCR technique. The administration of CBD significantly blocked the increase in motor activity and the increased number of rearings, rubbings and jumpings associated with cannabinoid withdrawal, and it normalized the decrease in the number of groomings. However, CBD did not change somatic signs in vehicle-treated animals. In addition, the anxiogenic-like effect observed in abstinent mice disappeared with CBD administration, whereas CBD induced an anxiolytic-like effect in non-abstinent animals. Moreover, CBD normalized gene expression changes induced by CP-55,940-mediated spontaneous withdrawal. The results suggest that CBD alleviates spontaneous cannabinoid withdrawal and normalizes associated gene expression changes. Future studies are needed to determine the relevance of CBD as a potential therapeutic tool for treating CUD.

용암해수를 이용한 해조류-식물 복합추출물의 숙취해소 효과

This study was conducted to evaluate the hangover relieving effect of algae and plant complex extract. The complex extract showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging effect in a concentration-dependent manner and high antioxidant capacity (59.48%) when administered at 120 μg/mL. In addition, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were increased according to the concentration of the complex extract. A locomotor activity test with an alcohol-complex extract mouse group showed improved motor activities over that of the alcohol-water group at 120 min post-administration. Blood was harvested from each mouse at 120 min post-administration then concentrations of alcohol and aldehyde were measured. The alcohol-extract treated group showed significantly lower (p<0.0001) alcohol (33.48 ± 0.59 μg/mL) and aldehyde (1.54 ± 0.13 μg/mL) concentrations than the alcohol-water treated group. These results suggest that the hangover relieving effects of complex extract results in increased motor activity of mice, which reduces the alcohol and aldehyde concentration in the blood.

Memantine treatment of juvenile rats with kaolin-induced hydrocephalus

Memantine is a selective, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that has previously been shown to have neuroprotective qualities in some animal models of neurologic disease. We hypothesized that memantine therapy would improve behavioral, neuropathological, and/or biochemical outcomes in juvenile rats with kaolin-induced hydrocephalus. Three-week old rats received an injection of kaolin (aluminum silicate) into the cisterna magna. Magnetic resonance imaging was performed one week later to assess ventricle size and stratify rats to three treatment groups. Rats were blindly treated daily for three weeks with saline or 10 or 30 mg/kg/day memantine. Behavior measures were performed weekly. Histologic and biochemical evaluations were performed at termination. Hydrocephalic rats showed no differences in weight among treatment groups. Memantine treatment stabilized ventricular enlargement in both low and high dose groups. The high dose group exhibited increased motor activity in open field chambers compared to the vehicle-treated group. However, there were no significant differences between the three hydrocephalic treatment groups for other behavioral tasks. Ventriculomegaly was associated with periventricular white matter damage. Glial fibrillary acidic protein (GFAP) content was higher in the low dose memantine group compared to vehicle-treated group, but there were no differences in GFAP-immunoreactive astrocytes or Iba-1- immunoreactive microglia between groups. Memantine therapy stabilized ventricular expansion and improved some behavioral measures but did not reduce brain tissue changes in juvenile rats with kaolin-induced hydrocephalus.

Regulation of Glutamate Signaling in the Sensorimotor Circuit by CASY-1A/Calsyntenin in Caenorhabditis elegans.

Locomotion is one of the most prominent behaviors in the nematode Caenorhabditis elegans. Neuronal circuits that ultimately produce coordinated dorso-ventral sinusoidal bends mediate this behavior. Synchronized locomotion requires an intricate balance between excitation and inhibition at the neuromuscular junctions (NMJ), the complex cellular and molecular mechanisms of which are not fully understood. Here, we describe the role of a cell adhesion molecule CASY-1, which functions to maintain this balance at the NMJ. In this study, we dissect out mechanisms by which the longer CASY-1A isoform could be affecting the excitatory cholinergic signaling at the NMJ by modulating the activity of sensory neurons. Mutants in casy-1 appear to have hyperactive sensory neurons, resulting in accelerated locomotion and motor circuit activity. These sensory neurons mediate increased motor activity via enhanced glutamate release. Using genetic, pharmacological, and optogenetic manipulations, we establish that CASY-1A is required to monitor the activity of these neurons. Our study illustrates a novel neuromodulatory role of CASY-1-mediated signaling in regulating the excitation-inhibition balance of the motor circuit.

F95. ASSESSING MANIC SYMPTOMS IN PATIENTS WITH SCHIZOPHRENIA USING THE YOUNG MANIA RATING SCALE

BackgroundVan Os and Kapur have proposed that the discrete categorical dichotomy of schizophrenia versus bipolar disorder be changed to a dimensional conceptualization. It is also known that manic symptoms can contribute to the clinical course and prognosis of schizophrenia. Hence, a domain for mania has been included in the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). However, the psychometric properties of the Young Mania Rating Scale (YMRS) have been little studied in subjects with schizophrenia.MethodsOne hundred and sixty-six inpatients with schizophrenia (diagnosed with DSM-5,2 age ≥ 18 years and ≤ 65 years, and length of hospital stay ≥ 2 weeks) were enrolled from two mental hospitals in Korea. The Institutional Review Board approved the study protocol, and informed consent was given by all study subjects before the start of the study. The Korean version of the YMRS was used to evaluate the severity of manic symptoms. In addition, the domain for mania in the CRDPSS was used to evaluate presence or absence of manic symptoms (0–1, absence; 2–4, presence).ResultsThe average age and age-at-onset of the subjects were 46.5 (SD = 11.2) and 25.2 (SD = 13.2) years, respectively. Half were men (51.5%), and most were unmarried (79.1%), religiously affiliated (61.5%) and educated below high school graduate level (73.0%). The mean chlorpromazine equivalent dose of prescribed antipsychotics was 921.1 (SD = 952.0) mg. The mean total score on the YMRS was 7.3 (SD = 6.9) and the mean item scores were: 0.2 (SD = 0.4) for elevated mood, 0.1 (SD = 0.4) for increased motor activity, 0.1 (SD = 0.4) for sexual interest, 0.1 (SD = 0.4) for sleep, 0.4 (SD = 0.8) for irritability, 0.6 (SD = 1.2) for speech, 0.8 (SD = 1.1) for language, 2.0 (SD = 3.3) for content, 0.2 (SD = 0.7) for aggressive behavior, 1.0 (SD = 1.0) for appearance, and 1.8 (SD = 1.7) for insight. The Cronbach α for the 11 YMRS items was 0.66, which is considered an acceptable level of internal consistency. Moreover, only 4% (n = 7) of the 166 subjects had manic symptoms as assessed by the mania domain in the CRDPSS. A receiver operating characteristic curve (ROC) showed that the optimal cut-off score distinguishing schizophrenia patients with and without manic symptoms was 10 with a sensitivity of 88.3% and specificity of 75.6% (area under curve = 0.803, P = 0.012).DiscussionSince a 10 point total score on the YMRS represents a mild level of Clinical Global Impression (CGI) severity of mania, we may conclude that our threshold on the YMRS for identifying manic symptoms in patients with schizophrenia is reasonable. Hence it may be useful to investigate the evaluation of manic symptoms in patients with schizophrenia from the perspective of deconstructing psychoses.

Spatiotemporal Control of GPR37 Signaling and Its Behavioral Effects by Optogenetics.

Despite the progress in deorphanization of G Protein-Coupled Receptors (GPCRs), ≈100 GPCRs are still classified as orphan receptors without identified endogenous ligands and with unknown physiological functions. The lack of endogenous ligands triggering GPCR signaling has hampered the study of orphan GPCR functions. Using GPR37 as an example, we provide here the first demonstration of the channelrhodopsin 2 (ChR2)-GPCR approach to bypass the endogenous ligand and selectively activate the orphan GPCR signal by optogenetics. Inspired by the opto-XR approach, we designed the ChR2-GPR37 chimera, in which the corresponding parts of GPR37 replaced the intracellular portions of ChR2. We showed that optogenetic activation of ChR2/opto-GPR37 elicited specific GPR37 signaling, as evidenced by reduced cAMP level, enhanced ERK phosphorylation and increased motor activity, confirming the specificity of opto-GPR37 signaling. Besides, optogenetic activation of opto-GPR37 uncovered novel aspects of GPR37 signaling (such as IP-3 signaling) and anxiety-related behavior. Optogenetic activation of opto-GPR37 permits the causal analysis of GPR37 activity in the defined cells and behavioral responses of freely moving animals. Importantly, given the evolutionarily conserved seven-helix transmembrane structures of ChR2 and orphan GPCRs, we propose that opto-GPR37 approach can be readily applied to other orphan GPCRs for their deorphanization in freely moving animals.

GALVANIC MUD TREATMENT IN THE REHABILITATION OF PATIENTS WITH PAIN IN THE LOWER BACK

Purpose. Evaluati on of the effectiveness of complex restorati ve treatment with the inclusion of galvanic mud procedures in patients with pain in the lower back. Patients and methods. There were 30 patients (18 men and 12 women) with a diagnosis: lumbulgia or lumboeishalgia under observation. Patients underwent a course of rehabilitation on the basis of the Republican Hospital of Rehabilitation, Makhachkala. Against the background of standard therapy, galvanic mud procedures were included in the therapy. The effectiveness of the treatment was assessed by the control of pain assessment according to the VAS scale, the body mass index, the psychoemoti onal state of the HAM test, the tests of Schober and Thomayer were carried out. Results. After the complex treatment in patients, clinical and functional indices of the state of the neuromuscular apparatus Were noted, varying depending on gender. The results of the study showed that the intensity of the pain syndrome according to the VAS score in the compared groups before the rehabilitation differed significantly (5.4 ± 0.1 points in men and 6.16 ± 0.3 in women, (p <0.05), after completion of the course of treatment, the VAS score decreased statistically in both groups: in men 2.0 ± 0.4 points and in women 1.8 ± 0.1 points (p <0.05), but between groups of significant differences in the quantitative assessment of pain the syndrome was not revealed. In determining the mobility of the lumbar spine, the results of the Schober test with lumbargia as in men, and women were unreliably reduced, after treatment restored within the norm: in men before treatment, 3.46 ± 1.47 cm, after 5.3 ± 0.73 cm (p < 0.05), in women before treatment 3.95 ± 0.5 cm, after 5.35 ± 0.55 cm (p < 0.05).The analysis of the dynamics of the test results of Tomayer revealed unreliably significant differences before treatment in men = 24.8 ± 2.4 cm, in women = 21,6 ± 6,2 cm. After the course of treatment in both groups there was a significant improvement in the indices: in men = 5.23 ± 1.44 cm (p <0.05), in women 1.45 ± 0.87 cm (p < 0,05), but at the same time a reliable difference in the indices (p < 0.01). Conclusion. The conducted research has shown that carrying out galvanic mud procedures in a complex of treatment in patients with lower back pain positively influences the restoration of lumbar vertebral segment motor activity, as well as the psychoemotional state of the patient. In this case, women are more actively reduced pain and increased motor activity, but less significant indicators of the change in the psychological test.

Effects of Administration of Serotonin 5-HT1A Receptor Ligands into the Amygdala on the Behavior of Rats with Different Manifestations of Conditioned Reflex Fear

The neurotransmitter mechanisms underlying the individual/group characteristics of behavior in animals were studied by comparing the effects of modulation of serotoninergic transmission in the amygdala in rats with different manifestations of conditioned reflex fear (high- and low-freezing rats). Administration of a 5-HT1A receptor agonist (8-OH-DPAT, 0.3 μg/0.5 μl) into the basolateral amygdala before testing of a previously acquired classical defensive reflex decreased freezing time in response to sound in low-freezing animals and weakened the signs of conditioned reflex fear in response to the signal. Administration of the receptor antagonist (WAY-100635, 0.2 μg/0.5 μl) decreased freezing time during exploration of context and in response to sound in all rats, which probably occurred as a result of increases in motor activity and the occurrence of a panic-like state. Administration of both the agonist and antagonist before extinction sessions accelerated extinction of the reflex in high-freezing rats, though the mechanisms of the effects of different ligands were different. Administration of receptor antagonist before retraining prevented acquisition of conditioned reflex freezing in all rats. 5-HT1A receptors in the amygdala play a major role not only in the manifestations and repeat acquisition, but also the extinction of conditioned reflex fear. High-freezing rats, as compared with low-freezing animals, were more sensitive to administration of 5-HT1 receptor ligands into the amygdala in relation to extinction and repeat acquisition.

Reduced Mu Power in Response to Unusual Actions Is Context-Dependent in 1-Year-Olds.

During social interactions infants predict and evaluate other people’s actions. Previous behavioral research found that infants’ imitation of others’ actions depends on these evaluations and is context-dependent: 1-year-olds predominantly imitated an unusual action (turning on a lamp with one’s forehead) when the model’s hands were free compared to when the model’s hands were occupied or restrained. In the present study, we adapted this behavioral paradigm to a neurophysiological study measuring infants’ brain activity while observing usual and unusual actions via electroencephalography. In particular, we measured differences in mu power (6 – 8 Hz) associated with motor activation. In a between-subjects design, 12- to 14-month-old infants watched videos of adult models demonstrating that their hands were either free or restrained. Subsequent test frames showed the models turning on a lamp or a soundbox by using their head or their hand. Results in the hands-free condition revealed that 12- to 14-month-olds displayed a reduction of mu power in frontal regions in response to unusual and thus unexpected actions (head touch) compared to usual and expected actions (hand touch). This may be explained by increased motor activation required for updating prior action predictions in response to unusual actions though alternative explanations in terms of general attention or cognitive control processes may also be considered. In the hands-restrained condition, responses in mu frequency band did not differ between action outcomes. This implies that unusual head-touch actions compared to hand-touch actions do not necessarily evoke a reduction of mu power. Thus, we conclude that reduction of mu frequency power is context-dependent during infants’ action perception. Our results are interpreted in terms of motor system activity measured via changes in mu frequency band as being one important neural mechanism involved in action prediction and evaluation from early on.

An Interaction between Serotonin Receptor Signaling and Dopamine Enhances Goal-Directed Vigor and Persistence in Mice.

The functionally selective 5-HT2C receptor ligand SB242084 can increase motivation and have rapid onset anti-depressant-like effects. We sought to identify the specific behavioral effects of SB242084 treatment and elucidate the mechanism in female and male mice. Using a quantitative behavioral approach, we determined that SB242084 increases the vigor and persistence of goal-directed activity across different types of physical work, particularly when work requirements are demanding. We found this influence of SB242084 on effort, rather than reward to be reflected in striatal DA measured during behavior. Using in vivo fast scan cyclic voltammetry, we found that SB242084 has no effect on reward-related phasic DA release in the NAc. Using in vivo microdialysis to measure tonic changes in extracellular DA, we also found no changes in the NAc. In contrast, SB242084 treatment increases extracellular DA in the dorsomedial striatum, an area that plays a key role in response vigor. These findings have several implications. At the behavioral level, this work shows that the capacity to work in demanding situations can be increased, without a generalized increase in motor activity or reward value. At the circuit level, we identified a pathway restricted potentiation of DA release and showed that this was the reason for the increased response vigor. At the cellular level, we show that a specific serotonin receptor cross talks to the DA system. Together, this information provides promise for the development of treatments for apathy, a serious clinical condition that can afflict patients with psychiatric and neurological disorders.SIGNIFICANCE STATEMENT Motivated behaviors are modulated by reward value, effort demands, and cost-benefit computations. This information drives the decision to act, which action to select, and the intensity with which the selected action is performed. Because these behavioral processes are all regulated by DA signaling, it is very difficult to influence selected aspects of motivated behavior without affecting others. Here we identify a pharmacological treatment that increases the vigor and persistence of responding in mice, without increasing generalized activity or changing reactions to rewards. We show that the 5-HT2C-selective ligand boosts motivation by potentiating activity-dependent DA release in the dorsomedial striatum. These results reveal a novel strategy for treating patients with motivational deficits, avolition, or apathy.

КОРРЕКЦИЯ МЕТАБОЛИЧЕСКОГО СИНДРОМА У ЖЕНЩИН В ПЕРИМЕНОПАУЗЕ

Objective: Study of the peculiarities of correction of metabolic disorders in women of the perimenopausal period Methods: 77 women were surveyed in perimenopause with metabolic syndrome (MS). Conducted analysis of hereditary prevalence and reproductive function; used clinical trails, studied carbohydrate and lipid metabolism, hormonal status; anthropometry, monitoring of arterial pressure, ultrasound of pelvic organs and liver. Results: Heredity in patients was burdened with cardiovascular diseases (58.4%), obesity (46.8%), diabetes mellitus (38.9%) and oncological pathology (18.2%). All interviewees have not given due attention to eating and enjoyed of food rich in carbohydrates in easily digestible form (81.8%). Patients showed: an increase in the body mass index (BMI) with an average value of 32±2.3 kg/m2, abdominal obesity (100%), insulin resistance (96.1%), dyslipidemia (84.4%), endocrinopathy (58.4%), hyperglycemia (55.8%), arterial hypertension (50.6%), androgen-dependent manifestations (32.5%), "Negroid acanthosis" (31,2%), steatosis of the liver (41.6%). Correction MS included a rational diet, increased motor activity, the appointment Metfogamma and Inoclim. The re-examination showed stabilization of the weight, reliable HOMA index reduction, general cholesterol content, low-density lipoprotein, and an increase of high-density lipoprotein level (p<0.05). Vegetovascular manifestations eliminated in 54.5% of women. Conclusion: Timely diagnosis and correction of metabolic disorders in women of perimenopausal age normalizes the main metabolism, eliminates the manifestations of menopause syndrome and positively affects the quality of their lives. Keywords: Metabolic syndrome, insulin resistance, lipid metabolism, carbohydrate metabolism, menopause, rational nutrition.

Long-term outcomes of spinal neurostimulation in patients with critical lower limb ischemia

To evaluate long-term outcomes of spinal neurostimulation (SNS) in patients with critical lower limb ischemia (CLI). Long-term outcomes of SNS were assessed in 52 CLI patients. Changes of clinical status were considered by using of Rutherford R.B. et al. scale. Before and in 12 months after SNS percutaneous oxygen partial pressure (TO2, mm Hg) was measured at the affected lower limb at rest and in orthostatic test. Ankle-brachial index (ABI) was also determined. SNS improved clinical status in most cases through following effects: 1) reduced pain syndrome and increased motor activity; 2) skin ulcers healing due to increased TO2 and improved functional state of microcirculation. No augmentation of TO2 during orthostatic test at TO2 <10 mm Hg was associated with negative clinical dynamics after SNS (OR 3.2, CI 2.2-54.1, p=0.002). Coronary artery disease with supra-aortic vessels lesion was associated with reduced ABI after SNS (OR 2.1, CI 1.4-3.8, p=0.001).

The infant motor system predicts actions based on visual statistical learning

Motor theories of action prediction propose that our motor system combines prior knowledge with incoming sensory input to predict other people's actions. This prior knowledge can be acquired through observational experience, with statistical learning being one candidate mechanism. But can knowledge learned through observation alone transfer into predictions generated in the motor system? To examine this question, we first trained infants at home with videos of an unfamiliar action sequence featuring statistical regularities. At test, motor activity was measured using EEG and compared during perceptually identical time windows within the sequence that preceded actions which were either predictable (deterministic) or not predictable (random). Findings revealed increased motor activity preceding the deterministic but not the random actions, providing the first evidence that the infant motor system can use knowledge from statistical learning to predict upcoming actions. As such, these results support theories in which the motor system underlies action prediction.

Хирургическое лечение с использованием метода тотального эндопротезирования тазобедренного сустава в системе реабилитации детей подросткового возраста, страдающих детским церебральным параличом (ДЦП)

Purpose Improvement of the results of surgical rehabilitation of adolescent patients with cerebral palsy with subluxation and dislocation of the hip with the help of hip joint arthroplasty. Materials and methods The work is based on a retrospective analysis of the treatment outcomes in 12 children with cerebral palsy at the age of 13 to 17 years who underwent a total hip replacement surgery. The indication for the operation was the presence of a severe deformity of the joint components that could not be reconstructed and was accompanied by severe pain, loss of limb weight-bearing, significant limitation of motor abilities in patients over the age of 13 years. The components with cementless fixation were used. All patients underwent adductorotomy on the affected side. Results Neurological and vascular complications were not observed. Dislocation of the head and instability of the implant components was not observed. All patients showed an increased motor activity, relief of pain, a significant increase in the joint range of movements. Good and satisfactory functional results were obtained. The best results were obtained in level I-III patients according to the GMFCS system. Children of level IV achieved pain relief, improvement in the sitting posture, facilitation of care for them. Unsatisfactory results were not obtained. There were no complications during the operation and in the postoperative period. Conclusion According to the results, hip joint arthroplasty can be recommended for the rehabilitation of adolescent patients suffering from cerebral palsy.

Behavior Disorders Caused by Perinatal Hypoxia in Juvenile Rats and Their Correction with GABA Derivative.

We studied the effects of acute normobaric hypoxia on postnatal day 2 (model of preterm pregnancy) on reflex activity and behavior of juvenile male Wistar rats and the possibility of correction of behavioral deficit by administration of GABA derivative Salifen after hypoxia. It is shown, that perinatal hypoxia impaired righting reflex and forelimb grip strength and increased motor activity in juvenile male rats. Administration of Salifen for 14 days in a dose of 15 mg/kg improved reflex activity and behavior of rats, which indicates the prospect of further study of the therapeutic efficacy of this drug on models of neonatal encephalopathy.

Short-term results of hip endoprosthesis with hemiprosthesis after femoral neck fracture, maintaining joint lubrication in adult patients

INTRODUCTION: Femoral neck fracture is one of the most common traumas in adult patients. Usually, the patients with such fractures present with many accompanying diseases, i. e. polymorbidity. The majority of intraarticular femoral neck fractures are indicated for primary hip joint alloplastic surgery. Despite the higher operational risk compared to osteosynthesis, this procedure is preferred for the treatment of femoral neck fractures in patients over 75 years of age. The main aim of this study is to build-up optimal indications or guidelines for primary endoprosthesis with hemiprosthesis after femoral neck fractures and to justify the choice of an optimal hip hemiprosthetic implant. MATERIALS AND METHODS: An one-year study assessed the therapeutic effectiveness of the elliptical monoarticular endoprosthetic head use compared to monoarticular spherical and biarticular spherical endoprosthetic head applications based on three groups of criteria: subjective, radiographic, and functional in 167 patients with hemiarthroplasty. RESULTS: According to the criteria mentioned above, better therapeutic outcomes have been achieved with the use of the elliptical monoarticular endoprosthetic head. The results of the follow-up of these patients showed that up to the end of the first year after surgery, a progressive elevation in the Modified Harris Hip Score point system as well as a regression to the disappearance of spontaneous and provoked pain regardless of the endoprosthetic design was recorded. The visual analogue scale scores showed a natural decrease in pain sensation with the passing of time from the surgical intervention despite the increasing motor activity. CONCLUSION: The primary hip joint hemialoplasty is indicated for femoral neck fractures, Garden III or IV, in polymorbid patients over 75 years of age. The elliptical monoarticular endoprosthetic head shows better therapeutic results based on subjective, radiographic and functional criteria during the 12-month follow-up study.

Endosulfan and Cypermethrin Pesticide Mixture Induces Synergistic or Antagonistic Effects on Developmental Exposed Rats Depending on the Analyzed Behavioral or Neurochemical End Points.

Exposure to pesticides has been associated with neurodevelopmental toxicity. Usually people are exposed to mixtures of pesticides. However, most studies analyze the effects of individual pesticides. Developmental exposure to mixtures of pesticides may result in additive effects or in antagonistic or synergistic effects. The aim of this work was to compare the effects of developmental exposure of rats to cypermethrin or endosulfan with the effects of its mixture on cognitive and motor function and on some underlying mechanisms. Exposure to individual pesticides or the mixture was from gestational day 7 to postnatal day 21. We analyzed the effects, in males and females, on spatial learning and memory, associative learning, anxiety, motor coordination, and spontaneous motor activity. We also analyzed neuroinflammation and NMDA receptor subunits in hippocampus and extracellular GABA in cerebellum. Exposure to the mixture, but not to individual pesticides, impaired spatial memory in males, associative learning in females, and increased motor activity in males and females. This indicates a synergistic effect of cypermethrin and endolsufan exposure on these end points. In contrast, motor coordination was impaired by individual exposure to endosulfan or cypermethrin, associated with increased extracellular GABA in cerebellum, but these effects were prevented in rats exposed to the mixture, indicating an antagonistic effect of cypermethrin and endolsufan exposure on these end points. The results show different interaction modes (synergism or antagonism) of the pesticides, depending on the end point analyzed and the sex of the rats.

Changes in energy and motor activity: core symptoms of bipolar mania and depression?

Objective:To evaluate how well symptom rating scales differentiate bipolar disorder (BD) episode types.Methods:One hundred and six patients with BD were followed for 13 years. At each visit, the following clinical scales were administered: Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D) and Clinical Global Impressions scale for use in bipolar illness (CGI-BP). To perform a comparison between the affective states of BP, three time points in each patient’s follow-up period were chosen for evaluation: the most severe manic episode, the most severe depressive episode, and the euthymic period with least symptoms. Canonical discriminant analyses (CDA) were performed to identify which symptoms best discriminated episodes.Results:CDA revealed HAM-D was worse than YMRS and CGI-BP to discriminate mood states. The items evaluating increased motor activity in YMRS (2, increased motor activity/energy) and HAM-D (9, agitation) were the best to distinguish mania, depression, and euthymia. In contrast, HAM-D item 8 (retardation) and the HAM-D and YMRS items related to mood symptoms were less important and precise.Conclusion:Higher levels of energy or activity should be considered a core symptom of mania. However, our results do not confirm the association between a decrease in energy or activity and depression. HAM-D probably does not assess motor activity adequately.

Developmental Exposure to Pesticides Alters Motor Activity and Coordination in Rats: Sex Differences and Underlying Mechanisms.

It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin). Pesticides were administered once a day orally, in a sweet jelly, from gestational day 7 to post natal day 21. Spontaneous motor activity was assessed by an actimeter and motor coordination using the rotarod, when rats were adults. The effects were analyzed separately in males and females. Extracellular GABA in cerebellum and NMDA receptor subunits in hippocampus were assessed as possible underlying mechanisms of motor alterations. Motor coordination was impaired by developmental exposure to endosulfan, cypermethrin, and chlorpyrifos in females but not in males. The effect of endosulfan and cypermethrin would be due to increased extracellular GABA in cerebellum, which remains unaltered in male rats. Chlorpyrifos increased motor activity in males and females. Cypermethrin decreased motor activity mainly in males. In male rats, but not in females, expression of the NR2B subunit of NMDA receptor in hippocampus correlated with motor activity. These results show sex-specific effects of different pesticides on motor activity and coordination, associated with neurotransmission alterations. These data contribute to better understand the relationship between developmental exposure to the main pesticide families and motor disorders in children.

Working Memory and Motor Activity: A Comparison Across Attention-Deficit/Hyperactivity Disorder, Generalized Anxiety Disorder, and Healthy Control Groups

Converging findings from recent research suggest a functional relationship between attention-deficit/hyperactivity disorder (ADHD)-related hyperactivity and demands on working memory (WM) in both children and adults. Excessive motor activity such as restlessness and fidgeting are not pathognomonic symptoms of ADHD, however, and are often associated with other diagnoses such as generalized anxiety disorder (GAD). Further, previous research indicates that anticipatory processing associated with anxiety can directly interfere with storage and rehearsal processes of WM. The topographical similarity of excessive motor activity seen in both ADHD and anxiety disorders, as well as similar WM deficits, may indicate a common relationship between WM deficits and increased motor activity. The relationship between objectively measured motor activity (actigraphy) and PH and visuospatial WM demands in adults with ADHD (n = 21), adults with GAD (n = 21), and healthy control adults (n = 20) was examined. Although all groups exhibited significant increases in activity from control to WM conditions, the ADHD group exhibited a disproportionate increase in activity, while activity exhibited by the GAD and healthy control groups was not different. Findings indicate that ADHD-related hyperactivity is uniquely related to WM demands, and appear to suggest that adults with GAD are no more active relative to healthy control adults during a cognitively demanding laboratory task.