Coordination In Rats Research Articles

High-Fat Diet-Induced Blood-Brain Barrier Dysfunction: Impact on Allodynia and Motor Coordination in Rats.

The associations among increased pain sensitivity, obesity, and systemic inflammation have not been described as related to BBB dysfunctions. To analyze the metabolic, behavioral, and inflammatory effects of a high-fat diet (HFD) and ultrastructural modifications in brain regions, we used an in vivo experimental model. Adult male Wistar rats were randomly assigned to one of two conditions, an ad libitum control group or an HFD (60%)-fed group, for eight weeks. At the end of the protocol, glucose and insulin tolerance tests were performed. Additionally, we analyzed the response to a normally innocuous mechanical stimulus and changes in motor coordination. At the end of the protocol, HFD-fed rats presented increased HOMA-IR and metabolic syndrome (MetS) prevalence. HFD-fed rats also developed an increased nociceptive response to mechanical stimuli and neurological injury, resulting in impaired motor function. Hypothalamus and cerebellum neurons from HFD-fed rats presented with nuclear swelling, an absence of nucleoli, and karyolysis. These results reveal that HFD consumption affects vital brain structures such as the cerebellum, hippocampus, and hypothalamus. This, in turn, could be producing neuronal damage, impairing cellular communication, and consequently altering motricity and pain sensitivity. Although direct evidence of a causal link between BBB dysfunction and sensory-motor changes was not observed, understanding the association uncovered in this study could lead to targeted therapeutic strategies.

Exploring the therapeutic potential: Apelin-13's neuroprotective effects foster sustained functional motor recovery in a rat model of Huntington's disease.

Huntington's disease (HD) is a hereditary condition considered by the progressive degeneration of nerve cells in the brain, resultant in motor dysfunction and cognitive impairment. Despite current treatment modalities including pharmaceuticals and various therapies, a definitive cure remains elusive. Therefore, this study investigates the therapeutic potential effect of Apelin-13 in HD management. Thirty male Wistar rats were allocated into three groups: a control group, a group with HD, and a group with both HD and administered Apelin-13. Apelin-13 was administered continuously over a 28-day period at a dosage of around 30 mg/kg to mitigate inflammation in rats subjected to 3-NP injection within an experimental HD model. Behavioral tests, such as rotarod, electromyography (EMG), elevated plus maze, and open field assessments, demonstrated that Apelin-13 improved motor function and coordination in rats injected with 3-NP. Apelin-13 treatment significantly increased neuronal density and decreased glial cell counts compared to the control group. Immunohistochemistry analysis revealed reduced gliosis and expression of inflammatory factors in the treatment group. Moreover, Apelin-13 administration led to elevated levels of glutathione and reduced reactive oxygen species (ROS) level in the treated group. Apelin-13 demonstrates neuroprotective effects, leading to improved movement and reduced inflammatory and fibrotic factors in the HD model.

The Beneficial Role of Apigenin against Cognitive and Neurobehavioural Dysfunction: A Systematic Review of Preclinical Investigations.

Apigenin is a flavone widely present in different fruits and vegetables and has been suggested to possess neuroprotective effects against some neurological disorders. In this study, we systematically reviewed preclinical studies that investigated the effects of apigenin on learning and memory, locomotion activity, anxiety-like behaviour, depressive-like behaviour and sensorimotor and motor coordination in rats and mice with impaired memory and behaviour. We searched SCOPUS, Web of Science, PubMed and Google Scholar for relevant articles. A total of 34 studies were included in this review. The included studies revealed that apigenin enhanced learning and memory and locomotion activity, exhibited anxiolytic effects, attenuated depressive-like behaviour and improved sensorimotor and motor coordination in animals with cognitive impairment and neurobehavioural deficit. Some of the molecular and biochemical mechanisms of apigenin include activation of the ERK/CREB/BDNF signalling pathway; modulation of neurotransmitter levels and monoaminergic, cholinergic, dopaminergic and serotonergic systems; inhibition of pro-inflammatory cytokine production; and attenuation of oxidative neuronal damage. These results revealed the necessity for further research using established doses and short or long durations to ascertain effective and safe doses of apigenin. These results also point to the need for a clinical experiment to ascertain the therapeutic effect of apigenin.

Therapeutic effects of cinnamon bark oil on sciatic nerve injury in rats.

The aim of this study was to investigate the effects of cinnamon bark essential oil (CBO) on analgesia, motor activity, balance, and coordination in rats with sciatic nerve damage. Rats were divided into three groups as simply randomized. The right sciatic nerve (RSN) of the Sham group was explored. Only vehicle solution was applied for 28 days. The RSN of the sciatic nerve injury (SNI) group was explored. Damage was created by unilateral clamping, and vehicle solution was applied for 28 days. The RSN of the sciatic nerve injury+cinnamon bark essential oil (SNI+CBO) group was explored. SNI was created by unilateral clamping and CBO was applied for 28 days. In the experiment study, motor activity, balance, and coordination measurements were made with rotarod and accelerod tests. A hot plate test was performed for analgesia measurements. Histopathology studies were carried out with the sciatic nerve tissues. In the rotarod test, there was a statistically significant difference between the SNI group and the SNI+CBO group (p<0.05). According to the accelerod test findings, there was a statistically significant difference between the SNI group with the Sham and SNI+CBO groups. In the hot plate test, there was a statistically significant difference between the SNI group with the Sham and SNI+CBO groups (p<0.05). In comparison to the Sham group and the SNI group, the SNI+CBO group was shown to have the greatest expression level of vimentin. We have concluded that CBO can be used as an adjuvant treatment in cases of SNI, increased pain, nociception, impaired balance, motor activity, and coordination. Our results will be supported by further studies.

Cerebellar fastigial nucleus histamine and its H2 but not H1 receptors might inhibit acetic acid-induced visceral nociception and improve motor coordination in rats: role of opioid system.

The cerebellum and its deep nuclei contribute to the regulation of important functions including motor coordination and pain. Histamine modulates some functions of the fastigial nucleus (FN) such as motor coordination. In this study, by application of histamine and activation of its H1 and H2 receptors, the FN processing of visceral pain, general locomotor activity and motor coordination were targeted. The possible mechanism of action was followed by the inhibition of opioid receptors. The right and left sides of the FN were surgically implanted with guide cannulas. Immediately after an intraperitoneal injection of acetic acid (1.00 mL, 1.00%), the first writhing onset latency and the writhing number over 60 min were recorded. Open-field and rotarod tests were applied for general locomotor and motor coordination assessment, respectively. Histamine and dimaprit (H2 receptor agonist) increased first writhing onset latency, decreased the writhing number and increased falling time from the rod. These effects were prevented by ranitidine (H2 receptor antagonist) pre-treatment. Significant alterations were not observed by histamine H1 receptor agonist (2-pyridylethylamine) and antagonist (mepyramine). Naloxone, with no effect on falling time from the rod, inhibited the antinociceptive effects of histamine and dimaprit. Beam break number was not affected by the above-mentioned treatments. Based on the results, it can be suggested that histamine H2, but not H1 receptors at the FN might have had an inhibitory role on acetic acid-induced visceral pain and improved motor coordination. The antinociception, but not motor coordination might be mediated by FN opioid receptors.

The Central Medial Thalamic Nucleus Facilitates Bilateral Movement Execution in Rats

Intralaminar thalamic nuclei, including the central medial nucleus (CMT), have been classically implicated in the control of attentional functional states such as sleep-wake transitions. In rodents, the CMT innervates large cortical and subcortical areas bilaterally, including sensorimotor regions of the cortex and striatum, but its contribution to motor function, which regularly develops in faster temporal scales than attentional states, is still far from being completely understood. Here, by using a novel behavioral protocol to evaluate bilateral coordination in rats, combined with electrophysiological recordings and optogenetic manipulations, we studied the contribution of the CMT to motor control and coordination. We found that optogenetic stimulation of the central region of the CMT produced bilateral recruitment of neural activity in the sensorimotor cortex and striatum. The same type of stimulations produced a significant increase in bilateral movement coordination of the forelimbs accompanied by a decrease in movement trajectory variability. Optogenetic inactivation of the CMT did not affect motor execution but significantly increased execution times, suggesting less interest in the task. Altogether, our results indicate that brief CMT activations create windows of synchronized bilateral cortico-striatal activity, suitable to facilitate motor coordination in temporal scales relevant for motor execution.

Positive GABAA receptor modulating steroids and their antagonists: Implications for clinical treatments.

GABA is the main inhibitory neurotransmitter in the brain and GABAergic transmission has been shown to be of importance for regulation of mood, memory and food intake. The progesterone metabolite allopregnanolone (Allo) is a positive GABAA receptor modulating steroid with potent effects. In humans, disorders such as premenstrual dysphoric disorder (PMDD), hepatic encephalopathy and polycystic ovarian syndrome are associated with elevated Allo levels and increased negative mood, disturbed memory and increased food intake in some individuals. This is surprising because Allo shares many properties with benzodiazepines and is mainly considered to be anxiolytic and anti-depressant. However, it is well established that, in certain individuals, GABAA receptor activating compounds could have paradoxical effects and thus be anxiogenic in low physiological plasma concentrations but anxiolytic at high levels. We have demonstrated that isoallopregnanolone (Isoallo), the 3β-OH sibling of Allo, functions as a GABAA receptor modulating steroid antagonist (GAMSA) but without any effects of its own on GABAA receptors. The antagonistic effect is noted in most GABAA subtypes investigated in vitro to date. In vivo, Isoallo can inhibit Allo-induced anaesthesia in rats, as well as sedation or saccadic eye velocity in humans. Isoallo treatment has been studied in women with PMDD. In a first phase II study, Isoallo (Sepranolone; Asarina Pharma) injections significantly ameliorated negative mood in women with PMDD compared with placebo. Several GAMSAs for oral administration have also been developed. The GAMSA, UC1011, can inhibit Allo induced memory disturbances in rats and an oral GAMSA, GR3027, has been shown to restore learning and motor coordination in rats with hepatic encephalopathy. In humans, vigilance, cognition and pathological electroencephalogram were improved in patients with hepatic encephalopathy on treatment with GR3027. In conclusion GAMSAs are a new possible treatment for disorders and symptoms caused by hyperactivity in the GABAA system.

Therapeutic potential of diosmin, a citrus flavonoid against arsenic-induced neurotoxicity via suppression of NOX 4 and its subunits.

OBJECTIVES:Water contaminated with arsenic affected millions of people worldwide and arsenic exposure is related to various neurological disorders. Hence, the current study was planned to investigate the neuroprotective activity of diosmin (DSN) against arsenic induced neurotoxicity as an attempt to identify therapeutic intervention to combat arsenicism.MATERIALS AND METHODS:Sodium arsenite an inducer of neurotoxicity was administered orally (13 mg/kg) and DSN treatment at two selected doses (50 and 100 mg/kg) was done for 21 days. Behavioral and biochemical variations were examined by various parameters. Furthermore, histopathological and immunohistochemistry studies were done with the brain sections.RESULTS:The behavioral studies evidenced that arsenic has suppressed the exploratory behavior and motor coordination in rats and DSN treatment has recovered the behavioral changes to normal. Arsenic administration has also found to induce oxidative stress and DSN co-treatment has ameliorated the oxidative stress markers. Interestingly, depleted levels of neurotransmitters were observed with the arsenic and it was restored back by the DSN treatment. Histopathological alterations like pyknosis of the neuronal cells were identified with arsenic exposure and subsided upon DSN co administration. Immunohistochemical studies have revealed the expression of NOX4 and its gp91phox and P47phox subunits and its suppression by DSN treatment may be the key therapeutic factor of it.CONCLUSIONS:Treatment with DSN showed a beneficial effect in protecting against arsenic-induced neurotoxicity by suppressing the toxicity changes and the antioxidant effect of DSN might be attributed to its ability of suppressing NOX4 and its subunits.

Chronic Hyponatremia Disrupts Gait Coordination in Rats that Persists Following Correction of Hyponatremia

Multiple epidemiologic studies have associated chronic hyponatremia with bone fractures. Potential etiologies of the increased fracture rate are both metabolic (bone resorption leading to increased bone fragility) and neural (increased falls). Studies in humans and rats have found that hyponatremia causes alterations in gait, implicating gait instability as a potential cause of the increased fall rate in humans. Previous studies in rats indicated that the alterations in gait were reversible following correction of hyponatremia, but in these studies the hyponatremia was maintained for relatively short periods (3–4 weeks). Whether alterations in gait produced by more chronic hyponatremia can also be reversed by correction of hyponatremia has not been studied. The present studies directly address this question. 22‐month‐old F344BN F1‐hybrid rats were made hyponatremic using desmopressin continuous infusion while fed a liquid diet. After 4, 8 or 12 weeks (wks) of chronic hyponatremia, a cohort of the hyponatremic rats after each time point were corrected to a normal [Na+] by removal of the desmopressin minipumps and allowed to recover for 8 wks. Gait was assessed using the CatWalk apparatus (Noldus Inc, NE) at baseline (NN, [Na+]=142±6.2 mmol/L, n =67), after sustained hyponatremia (HN, 4 wks: [Na+]=111±4.7 mmol/L, n=16; 8 wks: [Na+]=107±4.0 mmol/L, n =13; 12 wks: [Na+]=114±4.7 mmol/L, n =18), 8 weeks after correction of the hyponatremia (HC, [Na+]=140±3.0 mmol/L, n =7, 7, 9), and in a group of equivalently aged normonatremic control rats (12 wks, n=9). Locomotor performance of all rats was compared to baseline performance. The results confirmed that chronic hyponatremia caused a significant disruption in gait coordination, as assessed by measurement of the delay (msec) between left forelimb and right hindlimb initial contact: NN=−13.66±0.42 msec; 4‐wk HN=−17.20±0.90 (p=0.02); 8‐wk HN=−21.21±1.31 (p&lt;0.001); 12‐wk HN=−19.50±1.18 (p&lt;0.001), while 12‐wk normonatremic control rats were no different from baseline: −12.17±2.19 (p=0.35). Correction of hyponatremia returned the abnormalities in gait coordination to baseline levels after 4 wks of hyponatremia, but not after 8 and 12 wks of sustained hyponatremia: 4‐wk HC=−11.78±1.58 (p=0.21); 8‐wk HC=−19.45±1.32 (p=0.02); 12‐wk HC=−21.12±1.80 (p&lt;0.001). These results confirm previous results that gait is altered by chronic hyponatremia in rats, and that these defects are reversible after short periods of hyponatremia. However, longer periods of sustained hyponatremia caused greater disruptions of gait coordination, which did not return to baseline normonatremic levels following correction of hyponatremia. Our findings therefore suggest the possibility that chronic hyponatremia causes neuropathological changes in the brain that may lead to permanent alterations in limb coordination and subsequent gait instability, thereby increasing susceptibility to falls with resulting bone fractures.Support or Funding InformationSupported by NIH grant R01‐AG053506.

Central nervous system depressant activity of Jatamansi (Nardostachys jatamansi DC.) rhizome.

Background:Sleep disorders have a comparatively high prevalence worldwide and create a burden on the health system. Pharmacological agents used for insomnia are associated with considerable side effects. Therefore, searching for safe and effective agents from plant-based natural sources is a worthy effort. Jatamansi (Nardostachys jatamansi DC.) rhizome has been recommended for insomnia and mental conditions in the Indian system of medicine.Aim:This study aimed to determine central nervous system (CNS) depressant activity of Jatamansi (N. jatamansi) rhizome on experimental animals.Materials and methods:Gross behavior study and open field test (locomotor activity) were performed by using Charle’s foster albino rats whereas rota-rod test and pentobarbital-induced sleep test in Swiss albino mice. Animals were divided into 3 groups (per model) having six animals in each group. The control group was treated with water, the standard group with diazepam and the test drug with powder of N. Jatamansi rhizome. Results were calculated by one-way ANOVA and post hoc test with P < 0.05 as significant.Results:Data suggested that Jatamansi did not produce a significant effect on the behavior of animals. It reduced the horizontal activity significantly (P < 0.001) in the open field apparatus. The test drug did not show a significant decrease in latency of fall-off time in rota-rod performance in mice. Still, it exerted a significant effect by a reduction in latency of onset of sleep (P < 0.01) and also extended the total duration of sleep (P < 0.05) in albino mice in comparison to the control group.Conclusion:This study shows that Jatamansi rhizome powder possesses CNS depressant activity without affecting gross behavior and muscle coordination in rats.

Propriospinal Neurons of L3-L4 Segments Involved in Control of the Rat External Urethral Sphincter

Coordination of activity of external urethral sphincter (EUS) striated muscle and bladder (BL) smooth muscle is essential for efficient voiding. In this study we examined the morphological and electrophysiological properties of neurons in the L3/L4 spinal cord (SC) that are likely to have an important role in EUS-BL coordination in rats. EUS-related SC neurons were identified by retrograde transsynaptic tracing following injection of pseudorabies virus (PRV) co-expressing fluorescent markers into the EUS of P18-P20 male rats. Tracing revealed not only EUS motoneurons in L6/S1 but also interneurons in lamina X of the L6/S1 and L3/L4 SC. Physiological properties of fluorescently labeled neurons were assessed during whole-cell recordings in SC slices followed by reconstruction of biocytin-filled neurons. Reconstructions of neuronal processes from transverse or longitudinal slices showed that some L3/L4 neurons have axons projecting toward and into the ventro-medial funiculus (VMf) where axons extended caudally. Other neurons had axons projecting within laminae X and VII. Dendrites of L3/L4 neurons were distributed within laminae X and VII. The majority of L3/L4 neurons exhibited tonic firing in response to depolarizing currents. In transverse slices focal electrical stimulation (FES) in the VMf or in laminae X and VII elicited antidromic axonal spikes and/or excitatory synaptic responses in L3/L4 neurons; while in longitudinal slices FES elicited excitatory synaptic inputs from sites up to 400 μm along the central canal. Inhibitory inputs were rarely observed. These data suggest that L3/L4 EUS-related circuitry consists of at least two neuronal populations: segmental interneurons and propriospinal neurons projecting to L6/S1.

A novel GABAB receptor positive allosteric modulator, ASP8062, exerts analgesic effects in a rat model of fibromyalgia

The gamma-aminobutyric acid type B (GABAB) receptor agonist, the sodium salt of gamma-hydroxybutyrate (GHB), significantly improved pain, sleep disturbance and fatigue in fibromyalgia (FM) patients. However, the use of GABAB receptor agonists is limited by their undesirable side-effects. To clarify whether GABAB receptor positive allosteric modulator (PAM) approach would achieve analgesia with less side-effects than GABAB receptor agonist in FM, we investigated the potential of a novel GABAB receptor PAM, ASP8062, for FM treatment. We examined the in vitro profiles of ASP8062, the effects of a GABAB receptor PAM and an agonist on pain in a rat model of FM, and the sleep/wake cycle, EEG during sleep stages and motor coordination in rats. ASP8062 showed PAM activity on human and rat GABAB receptors. Oral administration of ASP8062 significantly reversed the decrease in muscle pressure threshold in reserpine-induced myalgia rats. The analgesic effects of ASP8062 were significantly blocked by a GABAB receptor antagonist. ASP8062 had a significant effect on motor coordination at a 1000-fold higher dose than the analgesic dose in rats. ASP8062 significantly decreased total REM sleep time and frequency of sleep interruptions, and increased the power in delta waves frequency during non-REM sleep in rats. ASP8062, a novel GABAB receptor PAM, has therapeutic potential to exert analgesic effects with less side-effects compared to GABAB receptor agonists in patients with FM.

Functional and pharmacological analysis of agmatine administration in different cerebral ischemia animal models

Agmatine (AgM, 100 mg/kg i.p.) effect was tested in parallel at two animal models of cerebral ischemia – rat MCAO model (60′/24 h, 60′/48 h, 90′/24 h, 90′/48 h) and gerbil global ischemia (10′) model, administrated 5 min after reperfusion. Aim was to evaluate AgM effect on functional outcome 24 and 48 h after MCAO on neurological and sensor-motor function, and coordination in rats. AgM administration significantly reduced infarct volume, improved neurological score and improved post-ischemic oxidative status. Results of behavioral tests (cylinder test, beam walking test, and adhesive removal test) have shown very effective functional recovery after AgM administration.Efficiency of AgM administration in gerbils was observed in forebrain cortex, striatum, hippocampus, and cerebellum at the level of each examined oxidative stress parameter (nitric oxide level, superoxide production, superoxide dismutase activity, and index of lipid peroxidation) measured in four different time points starting at 3 h up to 48 h after reperfusion. The highest levels were obtained 6 h after the insult. The most sensitive oxidative stress parameter to AgM was nitric oxide.Additionally, we performed pharmacological analysis of AgM on rat isolated common carotid arteries. The findings imply that mixed population of potassium channels located on the smooth muscle cells was involved in common carotid artery response to AgM, with predominance of inward rectifying K+ channels. In our comparative experimental approach, judged by behavioral, biochemical, as well as pharmacological data, the AgM administration showed an effective reduction of ischemic neurological damage and oxidative stress, hence indicating a direction towards improving post-stroke recovery.

Kinematic analysis of bimanual movements during food handling by head-fixed rats.

Bimanual coordination, in which both hands work together to achieve a goal, is crucial for the basic needs of life, such as gathering and feeding. Such coordinated motor skill is highly developed in primates, where it has been most extensively studied. Rodents also exhibit remarkable dexterity and coordination of forelimbs during food handling and consumption. However, rodents have been less commonly used in the study of bimanual coordination because of limited quantitative measuring techniques. In this article we describe a high-resolution tracking system that enables kinematic analysis of rat forelimb movement. The system is used to quantify forelimb movements bilaterally in head-fixed rats during food handling and consumption. Forelimb movements occurring naturally during feeding were encoded as continuous three-dimensional trajectories. The trajectories were then automatically segmented and analyzed, using a novel algorithm, according to the laterality of movement speed or the asymmetry of movement direction across the forelimbs. Bilateral forelimb movements were frequently observed during spontaneous food handling. Both symmetry and asymmetry in movement direction were frequently observed, with symmetric bilateral movements quantitatively more common. The proposed method overcomes a limitation in the precise quantification of bimanual coordination in rodents. This enables the use of powerful rodent-based research tools such as optogenetics and chemogenetics in the further investigation of neural mechanisms of bimanual coordination. NEW & NOTEWORTHY We describe a new method for quantifying and classifying three-dimensional, bilateral forelimb trajectories in head-fixed rats. The method overcomes limits on quantifying bimanual coordination in rats. When applied to kinematic analysis of food handling behavior, continuous forelimb trajectories were automatically segmented and classified. Bilateral forelimb movements were observed more frequently than unilateral movements during spontaneous food handling. Both symmetry and asymmetry in movement direction were frequently observed. However, symmetric bilateral forelimb movements were more common.

Evaluation of neuroprotective effects of wedelolactone and gallic acid on aluminium-induced neurodegeneration: Relevance to sporadic amyotrophic lateral sclerosis

Al exposure causes an alteration in the several ions in the body and causes toxicity. Such as apoptosis, oxidative stress, disruption in neuronal transport, mitochondrial damage, excitotoxicity, generation of inflammatory mediators, and microglial activation. These multiple mechanisms lead to the several neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (sALS). The study aims to unravel the mechanisms behind the neuroprotective effects of wedelolactone (WL) and gallic acid (GA) against aluminium-induced neurodegeneration and thereby to unlock a platform to find a cure for sALS. We studied the neuroprotective effects of WL (100 & 200 mg/kg) and GA (100 & 200 mg/kg) using aluminium chloride (AlCl3)-induced neurodegeneration model. The study was conducted using male Wistar rats. We assessed the effects of WL and GA on motor learning ability, motor coordination, locomotor activity, cytokine production, BDNF, glutathione peroxidase (GPx), m-calpain, caspase-3 inhibition and L-glutamate level. The study suggests that the treatment with WL and GA could protect the motor neurons from the toxicity that caused by Al via improving the antioxidant status, BDNF, and by preventing glutamate excitotoxicity. Also, WL and GA are found to be effective in inhibiting caspase-3 activation and downregulating inflammatory cytokines. WL and GA also found effective in improving the motor learning abilities and motor coordination in rats. The protective effects of the WL and GA were further confirmed from histopathological results. WL and GA prevent the neurofibrillary tangle formation and neuronal damage. The study concluded that the WL and GA were dose-dependently effective in managing the AlCl3-induced neurodegeneration.

Face validity of a pre-clinical model of operant binge drinking: just a question of speed.

Binge drinking (BD) is often defined as a large amount of alcohol consumed in a 'short' period of time or 'per occasion'. In clinical research, few researchers have included the notion of 'speed of drinking' in the definition of BD. Here, we aimed to describe a novel pre-clinical model based on voluntary operant BD, which included both the quantity of alcohol and the rapidity of consumption. In adult Long-Evans male rats, we induced BD by regularly decreasing the duration of ethanol self-administration from 1-hour to 15-minute sessions. We compared the behavioral consequences of BD with the behaviors of rats subjected to moderate drinking or heavy drinking (HD). We found that, despite high ethanol consumption levels (1.2g/kg/15minutes), the total amounts consumed were insufficient to differentiate HD from BD. However, consumption speed could distinguish between these groups. The motivation to consume was higher in BD than in HD rats. After BD, we observed alterations in locomotor coordination in rats that consumed greater than 0.8g/kg, which was rarely observed in HD rats. Finally, chronic BD led to worse performance in a decision-making task, and as expected, we observed a lower stimulated dopaminergic release within nucleus accumbens slices in poor decision makers. Our BD model exhibited good face validity and can now provide animals voluntarily consuming very rapidly enough alcohol to achieve intoxication levels and thus allowing the study of the complex interaction between individual and environmental factors underlying BD behavior.

Analysis of activity and motor coordination in rats undergoing stereotactic surgery and implantation of a cannula into the dorsal hippocampus

IntroductionStereotactic surgery is used to place electrodes or cannulas in the brain in order to study the function of several brain structures in preclinical research. The hippocampus has been extensively studied with this methodology due to its involvement in a wide range of neurological, cognitive, emotional, and affective disorders. However, the effects of stereotactic surgery on coordination and motor activity should be evaluated in order to determine whether this surgical procedure causes any neurological alterations that may bias the results of studies incorporating this technique. MethodsWe evaluated the effects of stereotactic surgery and implantation of a cannula into the hippocampus of female Wistar rats on the motor activity, forced swim, and rotarod tests. The stage of the oestrous cycle was included in the statistical analysis. ResultsStereotactic surgery had no impact on any of the motor activity variables assessed in the open field (squares crossed, time spent in grooming, and rearing), forced swim (turning behaviour, lateral swimming, latency to first immobility, and time spent immobile), and rotarod (latency to fall) tests, compared with intact rats. Regardless of surgical manipulation, rats in the metestrus and diestrus stages crossed a greater number of squares and displayed longer immobility times than those in the proestrus and estrus stages. ConclusionStereotactic surgery for cannula placement in the dorsal hippocampus does not affect coordination and motor activity in rats. We can therefore conclude that this procedure has no neurological complications that may interfere in the interpretation of results of studies applying this technique.

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.

Effect of liquid properties on swallowing and ventilation coordination in rats.

One aspect of rehabilitation in swallowing disorders is to change liquid properties. The objective of our study was to test how liquid properties could improve oropharyngeal dysphagia and swallowing and ventilation coordination in an animal model. Forty-two healthy male rats were distributed in six groups, including a control group. Rats were deprived of water for 24h and then each group was administered liquid with different properties: tap water, sugar water, sparkling water, salt water, cold water, and acidic water. Rats were studied without and with oropharyngeal dysphagia achieved by unilateral section of the hypoglossal nerve. Swallowing and ventilation were analyzed by barometric plethysmograph. In healthy rats, swallowing occurred during expiratory time for all liquid properties. Most deglutitions were during expiratory time for all liquid properties (88±12%) and were not modified. There was an increase in VT/TI during swallowing with sparkling water and cold water (P<.05). In the operated groups, rats had significantly fewer swallows with tap water (P<.05) and significantly more swallows with sparkling water (P<.001), sugar water (P<.001) and cold water (P<.001) during expiratory time. The mean inspiratory volume (VT/TI) increased with sparkling water (P<.05). Sparkling water seemed to improve swallowing and ventilation coordination in an animal model, to be confirmed in a study including patients with oropharyngeal dysphagia.

Contribution of hippocampal area CA1 to acetone cyanohydrin-induced loss of motor coordination in rats

IntroductionSome vegetable foodstuffs contain toxic compounds that, when consumed, favour the development of certain diseases. Cassava (Manihot esculenta Crantz) is an important food source, but it contains cyanogenic glucosides (linamarin and lotaustralin) that have been associated with the development of tropical ataxic neuropathy and konzo. In rats, intraperitoneal administration of acetone cyanohydrin (a metabolite of linamarin) produces neurological disorders and neuronal damage in the hippocampus. However, it is unknown whether hippocampal area CA1 plays a role in neurological disorders associated with acetone cyanohydrin. MethodA total of 32 male Wistar rats 3 months old were assigned to 4 groups (n=8 per group) as follows: vehicle (1μl physiological saline), and 3 groups with acetone cyanohydrin (1μl of 10, 15, and 20mM solution, respectively). The substances were microinjected intrahippocampally every 24hours for 7 consecutive days, and their effects on locomotor activity, rota-rod and swim tests were assessed daily. On the fifth day post-treatment, rats underwent further assessment with behavioural tests to identify or rule out permanent damage induced by acetone cyanohydrin. ResultsMicroinjection of acetone cyanohydrin 20mM resulted in hyperactivity, motor impairment, and reduced exploration from the third day of treatment. All concentrations of acetone cyanohydrin produced rotational behaviour in the swim test from the first day of microinjection. ConclusionThe hippocampal area CA1 is involved in motor alterations induced by microinjection of acetone cyanohydrin, as has been reported for other cassava compounds.