Measurement Of Motor Activity Research Articles

Inflammation-associated CNS pathways to fatigue in breast cancer patients

Breast cancer patients (∼40%) experience debilitating cancer-related fatigue (CRF), and efficacious treatment options are limited due in part to lack of understanding of the underlying pathophysiology. One promising avenue for treatment discovery is investigation of inflammation effects on CNS pathways involved in motivation and motor activity that may contribute to fatigue. Previous work shows that fatigue both during and after breast cancer treatment is associated with increased inflammation. Nevertheless, CNS mechanisms by which inflammation influences behavior in breast cancer patients are currently unknown. Our group and others have found that inflammation can alter the neural activation of and functional connectivity between brain regions that are involved in motivation and motor activity, including the basal ganglia and prefrontal cortex. Herein we present preliminary data from breast cancer patients who recently completed treatment (n = 16) indicating that patients with high inflammation exhibited decreased functional connectivity between ventral and dorsal striatal and prefrontal cortical regions, as measured by functional magnetic resonance imaging (fMRI). These alterations in corticostriatal circuitry were associated with reduced performance on objective measures of motivation and motor activity (r = 0.67, p

Combining actigraphy, ecological momentary assessment and neuroimaging to study apathy in patients with schizophrenia

BackgroundApathy can be defined as a reduction of goal-directed behavior and is a strong predictor for poor functional outcome in schizophrenia. However, no objective measure of apathy has been identified and assessment is limited to retrospective interview-based ratings. Here we aimed to identify more precise objective readouts of apathy for translational research and clinical practice. MethodsWe employed a combined approach including interview-based ratings of the two negative symptom factors apathy and diminished expression, actigraphy based measures of spontaneous motor activity and the evaluation of daily activities using ecological momentary assessment. Furthermore, a functional magnetic resonance imaging task for reward anticipation was applied to investigate shared and divergent neural correlates of interview-based and behaviorally measured apathy. ResultsWe found in 18 schizophrenia patients with high interview-based apathy levels that motor activity was negatively correlated with apathy but not with diminished expression. In contrast, measures of daily activities were not associated with apathy. Neural activation during reward anticipation revealed an association between hypoactivation of the ventral striatum and interview-based apathy as well as hypoactivation of the inferior frontal gyrus and motor activity level. ConclusionsSpontaneous motor activity is an objective readout of apathy, which was specific and not present for diminished expression. On a neural level, interview-based and objective measures of apathy showed divergent neural correlates in the cortical-striatal network, which suggests dissociable neural processes. Finally, motor activity provides a promising readout for quantifying apathy in both translational research and clinical practice.

Effect of a change in housing conditions on body weight, behavior and brain neurotransmitters in male C57BL/6J mice

The development of modern housing regimes such as individually ventilated cage (IVC) systems has become very popular and attractive in order to reduce spreading of pathogenic organisms and to lower the risk to develop a laboratory animal allergy for staff members. Additionally, optimal housing of laboratory animals contributes to improve animal health status and ensures high and comparable experimental and animal welfare standards. However, it has not been clearly elucidated whether 1) a change to IVC systems have an impact on various physiological phenotypic parameters of mice when compared to conventional, standard cages and 2) if this is further affected by changing from social to single housing. Therefore, we investigated the influence of a change in housing conditions (standard cages with social housing changed to standard or IVC cages combined with social or single housing) on body weight, behavior and a neurochemical fingerprint of male C57BL/6J mice. Body weight progression was significantly reduced when changing mice to single or social IVC cages as well as in single standard cages when compared to social standard housing. Automated motor activity measurement in the open field showed that mice maintained in social husbandry with standard cages displayed the lowest exploratory behavior but the highest activity difference upon amphetamine treatment. Elevated plus maze test revealed that a change to IVC single and social housing as well as single standard housing produced anxiety-related behavior when compared to maintenance in social standard housing. Additionally, postmortem neurochemical analysis of the striatum using high-performance liquid chromatography coupled to electrochemical detection showed significant differences in striatal dopamine and serotonin turnover levels. In summary, our data indicate a crucial influence of a change in housing conditions on several mouse phenotype parameters. We propose that the maintenance of well-defined housing conditions is mandatory to ensure reproducible and comparable results and contributes to the application of the 3R refinement principle in animal studies by contributing to welfare and hygienical standards.

The application of the Multi-Touch pad for the evaluation of the fine motor activity of the wrist

The objective of the present study was to elaborate the method for the evaluation of the fine motor activity of the wrist in the patients presenting with wrist movement disorders resulting from central hemiparesis and to demonstratee the reliability of such method through the calculation of the standard error of measurements and minimal the detectable change (MDC95%). The study population was comprised of 42 patients who had undergone ischaemic stroke and suffered from the impairment of the upper limb functions . The deficit of the fine motor skills was estimated with the use of the original multi-touch diagnostic technique. The results of the assessment were compared with those of the measurement of upper limb motor activity based on the validated scales, such as the Fugl-Meyer Assessment (FMA) scale and the Nine Hole Peg Test (PHT). The study with the application of the multi-touch method for diagnostics of the fine motor skills has demonstrated the high internal consistency of the measurements, with the Cronbach's Alpha Reliability Coefficient amounting to 0.98. The re-test reliability was high, with the ICC=0.98 (95% CI 0.97-0.99). The Spearman rank-order correlation with the locomotion scale estimates gave evidence of the good associative links, with the Fugl-Meyer Assessment scale correlation coefficient making 0.55-0.66 and the Nine Hole Peg Test findings being -0.7. The Minimal Detectable Change (MDC95%) for the multi-touch method was found to be 12.67%. The objective diagnostics of the fine motor skill disturbances with the use of the original multi-touch method has demonstrated its high reliability and a high degree of correlation with the estimates obtained with the application of the modern validated scales in the patients who had undergone ischaemic stroke. Therefore, this method can be recommended for clinical use.

Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task.

Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group.

Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor

Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy subjects (HCS, n=39) in the human Behavioral Pattern Monitor (hBPM) which quantifies motor activity and goal-directed behavior in an environment containing novel stimuli. Archival hBPM data from 17 schizophrenia patients were used in sensitivity and specificity analyses.Manic BD patients exhibited higher motor activity than HCS and higher novel object interactions. hBPM activity measures were not correlated with observer-rated symptoms, and hBPM activity was more sensitive in accurately classifying hospitalized BD subjects than observer ratings. Although the findings can only be generalized to inpatient populations, they suggest that increased energy, particularly specific and goal-directed exploration, is a distinguishing feature of BD mania and is best quantified by objective measures of motor activity. A better understanding is needed of the biological underpinnings of this cardinal feature.

Influence of Surrounding Medium on Metabolic Rates in Alpine Newts,Ichthyosaura alpestris, during Aquatic Phase

Abstract Measuring standard metabolic rates in newts remains a complicated task despite substantial methodological and technological advances in the field. We examined the influence of aquatic versus terrestrial conditions in respirometry chambers on measurements of respiratory gases and motor activity in Alpine Newts, Ichthyosaura alpestris, during their aquatic phase. Aquatic conditions during intermittent respirometry trials biased values of carbon dioxide production more than values of oxygen consumption, which caused marked differences in estimates of respiratory quotient. Placing newts in water increased their motor activity relative to terrestrial conditions during respirometry trials, which made obtaining representative estimates of standard metabolic rates complicated. We conclude that the absence of water, rather than aquatic conditions in respirometry chambers, produces more-accurate metabolic measurements in newts during their aquatic phase.

Measurements of Myosin-II Motor Activity During Cytokinesis in Fission Yeast.

Fission yeast myosin-II (Myo2p) represents the critical actin-based motor protein that drives actomyosin ring assembly and constriction during cytokinesis. We detail three different methods to measure Myo2p motor function. Actin-activated ATPases provide a readout of actomyosin ATPase motor activity in a bulk assay; actin filament motility assays reveal the speed and efficiency of myosin-driven actin filament gliding (when motors are anchored); myosin-bead motility assays reveal the speed and efficiency of myosin ensembles traveling along actin filaments (when actin is anchored). Collectively, these methods allow us to combine the standard in vivo approaches common to fission yeast with in vitro biochemical methods to learn more about the mechanistic action of myosin-II during cytokinesis.

Evaluation of subacute toxicity of methanolic/aqueous preparation of aerial parts of O. sanctum in Wistar rats: Clinical, haematological, biochemical and histopathological studies

Ethnopharmacological relevanceOcimum sanctum, commonly known as Holy Basil or Tulsi has been used in Ayurveda as a demulcent, stimulant, expectorant; in the treatment of bronchitis, skin infections, malaria, diarrhoea, dysentery, arthritis, gastric and inflammatory disorders. We have previously shown that methanolic/aqueous extract of O. sanctum did not induce genotoxicity and other toxic effects in acute oral toxicity study. In the present report, we have performed sub-acute toxicity of methanolic/aqueous preparation of O. sanctum in Wistar rats to evaluate whether it induced any chronic toxic effects. Materials and methodsIn subacute toxicity study, animals received O. sanctum extract (OSE) by oral gavage at the doses of 250, 500 and 1000mg/kg/day (n=5/group/sex) for 28 days. At the end of the study, the animals were sacrificed and evaluated for the effect of OSE on clinical, haematological, biochemical and histopathological parameters. ResultsThe rats treated with OSE did not show any change in body weight, food and water consumption, motor activity, sensory reactivity and foot splay measurements. There were no significant changes in haematological, pathological and biochemical parameters; and histopathology of tissues (liver, kidney, spleen, heart, and testis/ovary) among rats of either sex. OSE at a dose of 1000 mg/kg showed significant increase of Mean corpuscular hemoglobin (MCH) (19.8±0.8; 18.7±0.5) and mean corpuscular hemoglobin concentration (MCHC) (41.8±1.1; 39.3±0.7) in male and female rats in comparison to their respective controls (MCH: 17.7±0.3; 17.4±0.3; MCHC: 37.8±0.5; 36.1±0.2). Urine parameters (appearance, blood, nitrate, leucocyte, glucose, ketone, pH, protein and specific gravity) in both the male and female rats were comparable to their respective controls. In addition, no changes were observed in the vital organs of rats at macroscopic and microscopic levels. ConclusionsOur results showed that oral administration of OSE was not toxic to male and female Wistar rats upto the highest dose tested, thereby suggesting its clinical usefulness.

Psychomotor retardation is linked to frontal alpha asymmetry in major depression

BackgroundPsychomotor disturbances are a main clinical feature of major depressive disorder (MDD) but little is known about their EEG signature. One of the most replicated EEG findings in MDD is resting frontal asymmetry in the alpha band (FAA), which is thought to be a correlate of withdrawal behavior and reduced approach motivation. The purpose of this study was to assess psychomotor alterations, alpha band power, FAA and investigate the association between them. Methods20 MDD patients and 19 healthy subjects were enrolled. Alpha power and FAA scores were calculated from a resting state EEG. Wrist actigraphy was recorded from the non-dominant arm for 24 h and activity level scores (AL) were extrapolated from the wakeful periods. ResultsMDD patients had a left-lateralized frontal alpha activity and lower AL scores when compared to healthy subjects. A significant correlation was found between mean FAA and AL scores. A negative covariance between power in the lower alpha range and AL scores over the motor cortex bilaterally was detected. LimitationsRelatively small sample size. Patients were pharmacologically treated with antidepressants. ConclusionsThis study replicates the finding of left-lateralized FAA and lower AL scores in MDD patients, and establishes the first evidence of significant correlations between alpha power, FAA scores and measures of motor activity, which may be interpreted as an expression of impaired motivational drive in MDD.

STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.

Among the earliest volumes of this monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodrmal activity and fetal heartrate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include:within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physio-logical processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship.We pose a number of open questions for future research. Although the human fetus remains just out of reach, new technologies portend an era of accelerated discovery of the earliest period of development

P123. Correlation between EEG and clinical symptoms in depression

The underlying neurophysiological characteristics in Major Depressive Disorders(MDD) have been examined intensively for the past decades. Some studies have indicated pattern of electroencephalography(EEG) activity that distinguishes MDD patients from healthy subjects. However, the correlation between either clinical symptoms such as psychometric scales or sleeping disturbances and EEG activity were seldom investigated to date. Therefore this study aims to examine the correlation between depressive and psychomotor symptoms as well as sleeping disturbances with EEG power values and with current source density (CSD) analysis. 20 patients with MDD (mean age ± SD: 47 ± 12.57; female: 13) were compared with 20 age matched healthy subjects (mean age ± SD: 51 ± 10.5; female: 12). A 10 minutes eyes-closed resting state EEG (31 channels, additional ECG channel, 10/20 system) was applied to all participants. Impedances were kept below 5kΩ. EEG data were pre-processed using Brain Vision Analyzer (Brain Products, Gilching). EEG raw data were manually cleaned from movement artefacts. ECG and ocular artefacts were excluded via independent component analysis. Artefact free EEG was filtered with 0.5Hz high pass and 50Hz low pass and average was set as reference. EEG power and asymmetry indices were calculated from 8 minutes of artefact free data for each frequency and pooled over 6 electrode sites. One minute of artefact free data in each participant were exported for CSD analysis. Voxelwise CSD power was calculated for each frequency with Low Resolution Electromagnetic Tomography (LORETA) and pooled for cortical brodmann areas with relation to executive, attentional, motor and emotional functions. EEG power, asymmetry and CSD power were the subjects of Pearson’s correlation analyses to examine the interconnection with depressive symptoms (BDI, HDRS), psychomotor activity (Motor Agitation and Retardation Scale), psychomotor speed (TMT A), executive functions (TMT B, Stroop), Pittsburgh Sleep Quality Intervention (PSQI) and measurement of motor activity via actigraphy. There were significant positive correlations between TMT A and B and EEG power in beta and gamma bands widespread from central to posterior regions (p). Our results suggested that EEG power in beta and gamma frequency bands over central to posterior regions as well as higher power in delta and beta CSD in frontal regions can possibly predict the decreased performances in neuropsychological tests related to psychomotor speed and divided attention in MDD group. Sleeping disturbances are associated with higher power in beta and gamma EEG frequencies over temporoparietal regions. These findings confirm that depressive symptoms in patients with MDD have neurofunctional expressions in the EEG domain and may suggest further that cognitive and sleep disturbances are associated with activity in distinct neurofunctional areas.

Prosthetic reconstruction in high amputations of the upper extremity

Conventional upper arm prostheses are controlled via two surface electrodes that measure motor activity of two separately innervated muscle groups. The various prosthetic joints are chosen by co-contractions and controlled linearly by these two muscles. A harmonious and natural course of movements is not possible in this way. Overview regarding surgical, therapeutical and prosthetic options in high amputations of the upper extremity. Selective literature research including the authors' own experience in everyday clinical practice as well as a review of medical records. Selective nerve transfers of the amputated nerves of the brachial plexus to the remaining stump muscles can create up to six myosignals for intuitive and simultaneous control of the different prosthetic joints. In this way, an efficient and harmonious control of the prosthetic device is possible without the need to change between the different control levels. At the same time, possible neuromas are treated and painless wear of the prosthesis is achieved. Due to the resulting extended use of the prosthetic device, the demands regarding stump quality are increased. Thus, both surgically and by the means of the orthopedic technician a stable stump-socket connection should be achieved to enable optimal prosthetic function.

Different daily patterns of serum cortisol and locomotor activity rhythm in horses under natural photoperiod

Abstract The goal of the present study was to investigate the daily pattern of serum cortisol rhythm in relation to the total locomotor activity in horses housed in an individual box under a 12-hour light-dark cycle. Blood samples were collected at 3-hour intervals over a 48-hour period via an intravenous cannula inserted into the jugular vein in 5 Italian Saddle horses. In addition, the horses were equipped with Actiwatch Mini, actigraphy-based data loggers that record a digitally integrated measure of motor activity. The application of cosinor rhythmometry showed a daily rhythmicity of serum cortisol levels and locomotor activity. Both parameters showed a diurnal acrophase, at the beginning of photophase for cortisol anticipates of about 5 hours with respect to the acrophase of locomotor activity. The data on the distribution of acrophases have implications for the issue of causation. In conclusion, we found no influence of the rhythm of locomotor activity with the rhythm of serum cortisol.

Repeated measurements of motor activity in rats in long-term toxicity studies

Repeated measurements of motor activity in rats in long-term toxicity studies

Electroencephalographic and autonomic alterations in subjects with frequent nightmares during pre-and post-REM periods

Abnormal arousal processes, sympathetic influences, as well as wake-like alpha activity during sleep were reported as pathophysiological features of Nightmare Disorder. We hypothesized that in Nightmare Disorder, wake-like cortical activity and peripheral measures linked to arousals would be triggered by physiological processes related to the initiation of REM periods. Therefore, we examined electroencephalographic (EEG), motor and autonomous (cardiac) activity in a group of nightmare (NM) and healthy control (CTL) subjects during sleep-state-transitions while controlling for the confounding effects of trait anxiety. Based on the second-nights’ polysomnographic recordings of 19 Nightmare Disordered (NM) and 21 control (CTL) subjects, we examined the absolute power spectra focusing on the alpha range, measures of heart rate variability (HRV) and motor (muscle tone) activity during pre-REM and post-REM periods, separately. According to our results, the NM group exhibited increased alpha power during pre-REM, but not in post-REM, or stable, non-transitory periods. While CTL subjects showed increased HRV during pre-REM periods in contrast to post-REM ones, NM subjects did not exhibit such sleep state-specific differences in HRV, but showed more stable values across the examined sleep stages and less overall variability reflecting generally attenuated parasympathetic activity during sleep-state-transitions and during stable, non-transitory NREM states. These differences were not mediated by waking levels of trait anxiety. Moreover, in both groups, significant differences emerged regarding cortical and motor (muscle tone) activity between pre-REM and post-REM conditions, reflecting the heterogeneity of NREM sleep. Our findings indicate that NM subjects’ sleep is compromised during NREM–REM transitions, but relatively stabilized after REM periods. The coexistence of sleep-like and wake-like cortical activity in NM subjects seems to be triggered by REM/WAKE promoting neural activity. We propose that increased arousal-related phenomena in NREM–REM transitions might reflect altered emotional processing in NM subjects.

Measurement of Chaotic Dynamics for Two Types of Tapping as Voluntary Movements

We present examples for representation of chaos parameters in clinical medicine, and we demonstrate their diagnostic value. We show that in measuring motor activity of any biological system, we need to consider the actual superposition of the voluntary act (presence of intention and mechanisms for its achievement) and an inevitable chaotic element. We consider chaos parameters having significant informational value in the form of quasi-attractors.

Repeated measurements of motor activity in rats in long-term toxicity studies

IntroductionIn the light of 3R (replace, reduce, refine) principles in animal experimentation and increased focus on delayed effects of treatment on central nervous system, the incorporation of behavioural tests into standard toxicology studies as a complement or substitution of a stand-alone safety pharmacology study appears very attractive, but poses some challenges. In the present study, we evaluated the results of an open field test (standard part of the behavioural test batte- ries) incorporated into the 3-month regulatory toxicology study. MethodsThe study was performed in two rat strains most commonly used in toxicology studies (Wistar and Sprague Dawley (SprD)). Open field test was performed according to the standard protocol for stand-alone behavioural test (modified Irwin test) before the start of treat- ment (Day-7, “naïve” animals), on Day 2, inWeek 6 and inWeek 13 of treatment with saline. Results and DiscussionThere was no overall difference between strains, and onlyminor differenceswere detected at the individual time points. With regard to time effect, the average values for most of the parameters were comparable throughout the study but individual variability in the performance in the arena was increased at repeated measurements compared to the start. In conclusion, performance in the open field arena did not differ principally betweenWistar and SprD rats of both genders. However, individual variability in the behaviour in the open field arena increased with time. This has clear implications for deciding the appropriate group size for this type of study and has to be taken into account in the design of a toxicology study with integrated safety pharmacology endpoints.

Increased number of orexin/hypocretin neurons with high and prolonged external stress-induced depression

It has been found that dysregulation in the orexin/hypocretin (Ox/HCRT) neuropeptide system in the lateral hypothalamus (LHA) is known to affect sleep disorder, depression and motor activities. However, to date there is no common agreement regarding the resulting specific changes induced in the Ox system. In this study, we inject corticosterone to produce stress-induced depressed mice and investigate the Ox neuronal and corresponding behavioural changes. Different doses (10, 20, 50mg/kgbw) of corticosterone were injected in adult mice, and then were tested in the open field test, forced swim test, tail suspension test, elevated plus maze test and motor activity measurements to validate the depressed animal model. Significant dose-dependent behavioural changes were observed in correlation with the doses of corticosterone. The effect is most significant and robust in the high 50mg/kgbw dose group five weeks after injection. Interestingly, we found on average a reduction in motor activity during the 12-hour dark phase (awake) of the depressed mice and no significant change during the light phase (asleep). Finally, using confocal microscopy, immunofluorescence (IF) analysis shows a significant increase (∼20%) in the number of Ox neurons in the LHA of the depressed mice as compared to the age-matched controls. This study suggests that an increase in Ox neuronal signaling may be functionally linked to high and prolonged external stress-induced depression.

Antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rodents

BackgroundPainful neuropathy is the most common and debilitating complication of diabetes and results in hyperalgesia and allodynia. Hyperglycemia clearly plays a key role in the development and progression of diabetic neuropathy. Current therapeutic approaches are only partially successful and they are only thought to reduce the pain associated with peripheral neuropathy. Some natural products offer combined antioxidant, anti-inflammatory and antinociceptive properties that may help to treat in a more integrative manner this condition. In this regard, the purpose of this study was to investigate the antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rats and mice without glucose control as well as the possible mechanism of action involved in this effect.MethodsRats and mice were injected with 50 or 200 mg/kg streptozotocin, respectively, to produce hyperglycemia. The formalin test and von Frey filaments were used to assess the nociceptive activity. Rota-rod was utilized to measure motor activity and malondialdehyde assay to determine anti-oxidative properties.ResultsAfter 3 weeks of diabetes induction, chemical hyperalgesia was observed in streptozotocin-injected rats. Oral acute administration of 7-hydroxy-3,4-dihydrocadalin (0.3–30 mg/kg) decreased in a dose-dependent manner formalin-evoked hyperalgesia in diabetic rats. In addition, methiothepin (non-selective 5-HT receptor antagonist, 1 mg/kg, i.p.) and ODQ (guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (opioid receptor antagonist, 1 mg/kg, s.c.), prevented 7-hydroxy-3,4-dihydrocadalin-induced antihyperalgesic effect. The anti-hyperalgesic effect of 7-hydroxy-3,4-dihydrocadalin was similar to that produced by pregabalin (10 mg/kg, p.o.). Furthermore, oral acute administration of 7-hydroxy-3,4-dihydrocadalin (30 mg/kg) reduced streptozotocin-induced changes in malondialdehyde concentration from plasma samples. Unlike pregabalin, 7-hydroxy-3,4-dihydrocadalin did not affect motor activity. Six weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. At this time, oral administration of 7-hydroxy-3,4-dihydrocadalin (30 mg/kg) or pregabalin (10 mg/kg) reduced in a similar way tactile allodynia in diabetic rats. Finally, chronic oral administration of 7-hydroxy-3,4-dihydrocadalin (30-300 mg/kg, 3 times/week, during 6 weeks), significantly prevented the development of mechanical hyperalgesia and allodynia in streptozotocin-induced diabetic mice.ConclusionsData suggests that 7-hydroxy-3,4-dihydrocadalin has acute and chronic effects in painful diabetic neuropathy. This effect seems to involve antioxidant properties as well as activation of 5-HT receptors and inhibition of guanylyl cyclase enzyme.