Measures Of Locomotor Activity Research Articles

The olfactory nerve has a role in the body temperature and brain cytokine responses to influenza virus

Mouse-adapted human influenza virus is detectable in the olfactory bulbs of mice within hours after intranasal challenge and is associated with enhanced local cytokine mRNA and protein levels. To determine whether signals from the olfactory nerve influence the unfolding of the acute phase response (APR), we surgically transected the olfactory nerve in mice prior to influenza infection. We then compared the responses of olfactory-nerve-transected (ONT) mice to those recorded in sham-operated control mice using measurements of body temperature, food intake, body weight, locomotor activity and immunohistochemistry for cytokines and the viral antigen, H1N1. ONT did not change baseline body temperature (Tb); however, the onset of virus-induced hypothermia was delayed for about 13 h in the ONT mice. Locomotor activity, food intake and body weights of the two groups were similar. At 15 h post-challenge fewer viral antigen-immunoreactive (IR) cells were observed in the olfactory bulb (OB) of ONT mice compared to sham controls. The number of tumor necrosis factor α (TNFα)- and interleukin 1β (IL1β)-IR cells in ONT mice was also reduced in the OB and other interconnected regions in the brain compared to sham controls. These results suggest that the olfactory nerve pathway is important for the initial pathogenesis of the influenza-induced APR.

Determining stress-responsiveness in family groups of Atlantic salmon ( Salmo salar) using non-invasive measures

In this study, we examined variation in stress-responsiveness between 10 full sibling families of Atlantic salmon from a commercial breeding programme. Behavioural observations (locomotor activity during acute confinement and feeding response after placement in a novel environment) and cortisol release into the water were used as non-invasive markers of stress-responsiveness. Locomotor activity during acute stress was highly correlated with cortisol release rate, while feeding response did not correlate with either of the other two markers. Locomotor activity and cortisol release rate differed significantly between families, whereas feeding response did not. These results provide further support for hypothalamus-pituitary-interrenal responsiveness being a heritable (genetic) trait. Furthermore, results from an infectious pancreas necrosis virus (IPNV) challenge (carried out within the breeding programme from which our experimental fish originated) indicated a positive correlation between stress-responsiveness and mortality at the family level. In summary, the behavioural measure of locomotor activity during acute confinement provides a simple alternative measure of stress-responsiveness to physiological measures of cortisol, and families characterised by high stress-responsiveness showed increased susceptibility to IPNV.

Anxiolytic effect of a herbal medicine, yokukansan, in aged rats: Involvement of serotonergic and dopaminergic transmissions in the prefrontal cortex

Aim of the study Aging is thought to affect emotions including anxiety, and a herbal medicine, yokukansan (YKS), is used to treat emotional disturbances associated with age-related neurodegenerative disorders such as Alzheimer's disease, but its pharmacological properties have not been fully understood. The present study was designed to examine whether YKS improves age-related anxiety using F344/N aged rats. Moreover, the effects of YKS on liver function were examined. Materials and methods YKS was administered to 21-month-old aged rats for 3 months. Locomotor activity of young control (4 months old), aged control (24 months old), and YKS-treated aged rats was examined, and the anxiety-related responses of these animals were evaluated by counting the number of excrements during locomotor activity measurement and in the elevated plus-maze test. The extracellular concentrations of serotonin and dopamine in the prefrontal cortex (PFC) were also measured using a microdialysis technique. Moreover, concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and ammonia (NH 3) in plasma were measured. Results Although locomotor activity did not change among any experimental groups, the number of excrements was significantly increased in aged rats compared to young rats, and this increase was significantly improved by YKS treatment. Aged rats also showed significant decreases in time and frequency in the open arm of the elevated plus-maze, and these decreases were significantly improved by YKS treatment. Extracellular concentrations of serotonin and dopamine in the aged PFC were significantly decreased; serotonin was increased over the level of young rats and dopamine was partially improved by YKS treatment, respectively. In addition, YKS improved age-related increase in NH 3 concentration, but did not affect AST and ALT. Conclusions YKS has improving activity for age-related increased anxiety and enhances serotonergic and dopaminergic transmissions in the aged PFC. These mechanisms provide information important for the treatment of anxiety in the elderly. Furthermore, the present data confirm partially the Kampo concept “liver disease”.

Insulin-mediated cortical activity in the slow frequency range is diminished in obese mice and promotes physical inactivity

There is evidence from mouse models and humans that alterations in insulin action in the brain are accompanied by an obese phenotype; however, the impact of insulin with regard to behavioural aspects such as locomotion is unknown. To address insulin action in the brain with regard to cortical activity in distinct frequency bands and the behavioural consequences, the insulin signalling pathway was followed from the receptor to electrical activity and locomotion. Western blot analysis, electrocorticograms with intracerebroventricular (i.c.v.) application of insulin, and measurements of locomotor activity were performed in lean and obese, as well as Toll-like receptor (TLR) 2/4-deficient, mice. We show that insulin application i.c.v. into lean mice was accompanied by a profound increase in cortical activity in the slow frequency range, while diet-induced obese mice displayed insulin resistance. In parallel, insulin administered i.c.v. increased locomotor activity in lean mice, whereas a phosphatidylinositol-3 (PI3) kinase inhibitor or obesity abolished insulin-mediated locomotion. A potential candidate that links insulin signalling to locomotion is the Kv1.3 channel that is activated by PI3-kinase. Pharmacological inhibition of Kv1.3 channels that bypassed insulin receptor activation promoted activity. Moreover, mice deficient in TLR2/4-dependent signalling displayed an increase in cortical activity in the slow frequency range that was correlated with improved spontaneous and insulin-mediated locomotor activity. Our data provide functional evidence for a direct effect of insulin on brain activation patterns in the slow frequency bands and locomotor activity in lean mice, while in obese mice, insulin-mediated locomotion is blunted and further aggravates physical inactivity.

P.1.d.013 Prenatal stress increases an anxiety, and alters corticosterone response to 5-HT2A/C agonist in adult female offspring

Smith–Lemli–Opitz syndrome (SLOS) is a developmental disorder resulting from mutations to the Dhcr7 gene, which is required for cholesterol synthesis. Patients with SLOS typically exhibit a number of severe behavioral deficits and many are diagnosed with autistic spectrum disorder. Although the molecular pathophysiology underlying behavioral changes in SLOS and autism spectrum disorders is poorly understood, there is evidence for the involvement of the serotonergic system in SLOS and autism in general. Behavioral testing was undertaken to ascertain the basal behavioral differences between Dhcr7-heterozygous (HET) and wild-type control mice and explore the utility of a Dhcr7-HET mouse line in the development of new treatments for this disorder. Dhcr7-HET mice did not differ from wild-type control mice on basic measures of locomotor activity, anxiety and neuromuscular ability. However, female Dhcr7-HET mice at 6 months of age or older were significantly more likely to win on the social dominance tube test against an unfamiliar mouse. Pharmacological testing, using the 5-HT2A agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), showed increased head-twitch response in Dhcr7-HET mice, which was apparent from 6 months of age. No differences were found between the genotypes in testing for 5-HT1A agonist 8-OH-DPAT-induced hypothermia. These data indicate an underlying dysfunction of the 5-HT2A receptors in Dhcr7-HET mice that warrants further investigation to establish how this may relate to behavioral disturbances in human patients carrying Dhcr7 mutations.

Direct and indirect 5-HT receptor agonists produce gender-specific effects on locomotor and vertical activities in C57 BL/6J mice

It is well established that the dopamine (DA) and serotonin (5-HT) systems have extensive and complex interactions. However, the effects of specific 5-HT receptor agonists on traditionally DA-related behaviors remain unclear. Our goal in these studies was to characterize the effects of 5-HT receptor agonists on measures of locomotor activity and vertical rearing. The SSRIs fluoxetine and citalopram produced significant decreases in locomotor activity and vertical rearing at the highest doses used with females significantly more sensitive to citalopram. The 5-HT 1A agonist 8-OH-DPAT and the 5-HT 2C agonist MK 212 significantly decreased activity in both male and female mice, with females more sensitive to 8-OH-DPAT. In contrast, the 5-HT 1B agonist RU 24969 and the 5-HT 2A agonist DOI both increased activity, with DOI exhibiting differential effects with regard to sex. Finally, the 5-HT 3 agonist SR 57227 produced significant locomotor increases only in female mice at the lowest dose. The results of these experiments define locomotor profiles of several 5-HT agonists in male and female C57BL/6J mice, providing a foundation for further explorations of 5-HT receptor effects on activity.

Measurements of locomotor activity in hatchlings of the migratory locust Locusta migratoria: effects of intrinsic and extrinsic factors

Abstract. The effects of intrinsic and extrinsic factors on locomotor activity in crowd‐reared first‐stadium nymphs of the migratory locust Locusta migratoria are investigated under continuous light conditions using an actograph apparatus. Nymphs show monomodal or bimodal patterns of locomotor activity with respect to the time after the start of measurements, depending on the age. Locomotor activity is suppressed by the presence of grass in nymphs aged 0–2 days old but a peak of activity observed shortly after hatching is not suppressed. The results suggest that newly‐hatched nymphs may try to disperse from the hatching site. Nymphs show higher locomotor activity levels under moist conditions than under dry conditions during the first 5‐h period of measurements. This enhanced locomotor activity may constitute attempts to avoid high humidity. Under dim‐light conditions (2 × 10−2 Wm−2), locomotor activity is suppressed during the first half day and increases to a high level thereafter in both grass‐fed and unfed individuals. This increased activity might indicate a possible involvement of circadian rhythms. Background colour has no significant effect on the locomotor activity. The present study provides new aspects of behaviour in nymphs as well as baseline data for behavioural analysis of locust locomotion in relation to phase polyphenism.

Suppression of hippocampal cell proliferation by short‐term stimulant drug administration in adult rats

Sleep loss is known to potently suppress adult hippocampal cell proliferation and neurogenesis. Whether sleep suppression following acute administration of stimulant drugs also decreases hippocampal cell proliferation is not known. The present study examined the effect of three mechanistically distinct stimulants (caffeine, methamphetamine and modafinil) on cell proliferation. To maximize sleep suppression, these drugs were administered to rats (three i.p. injections, once every 4 h) during their sleep period (i.e. 12-h light phase). At the end of the light phase, 5-bromo-2'-deoxyuridine (200 mg/kg, i.p.) was injected and animals were killed 2 h later. Polygraphic recordings and locomotor activity measurements confirmed the wake-promoting and sleep-suppressing actions of each treatment. Results indicate that caffeine (20 mg/kg), methamphetamine (1.5 mg/kg) and modafinil (300 mg/kg) differentially suppressed sleep (45-91%) and selectively reduced cell proliferation in the hilus (12-44%), these results being significant for both caffeine and modafinil. When the same experiment was repeated in the dark (active) phase, the suppressant effect on hippocampal cell proliferation was either absent or greatly attenuated. In a further experiment, the effect of acute modafinil treatment in the light phase was shown to persist for 3 weeks after BrdU administration. We hypothesize that the differential effect of the stimulant drugs in the light vs. dark phase is attributable primarily to sleep suppression in the light. As abuse of stimulant drugs invariably leads to disrupted sleep in humans, our results suggest that they may, at least in part, decrease hippocampal neurogenesis via sleep loss and thereby adversely affect hippocampal-dependent processes.

Characterizing the Acute Cardiovascular Toxicities of Cocaine in Freely Moving Rhesus Monkeys

Cocaine (COC) abuse remains a significant public health problem with an estimated 2.4 million users in the United States alone (SAMHSA, 2007). COC is not only the most commonly reported illicit drug involved in emergency room (ER) visits, but COC‐related visits have increased ~160% from 1995 to 2005, with admissions most commonly attributed to chest pain resulting from increases in blood pressure (BP) and heart rate (HR). These studies were aimed at characterizing the acute cardiovascular (CV) effects of COC in freely moving rhesus monkeys (n=4). Implantable radio‐telemetric probes (DSI; D70‐PCT) were used to collect continuous measures of BP, HR, ECG parameters, body temperature, and locomotor activity for a period of 2 hrs after COC administration (0, 0.1, 0.32, 1.0, and 3.2 mg/kg; iv). BP and HR were the most reliable indicators of COC intoxication, with dose‐dependent increases in BP and HR (magnitude and duration) observed following doses of 0.32‐3.2 mg/kg COC. These changes in CV activity are not only similar to those observed in the ER, but also provide a model to compare the effectiveness of currently used, and novel therapeutics for the treatment of acute COC‐induced CV toxicity.Supported by NIDA grant DA 023213

Genetically controlled differences in behaviour between cycling and non-cycling populations of field vole (Microtus agrestis)

Behavioural tests measuring locomotor activity of single individuals and groups of animals of the same sex have been performed on samples of Microtus agrestis from a cycling population in northern Sweden and a non-cycling population from south Sweden. The activity was higher for animals from the northern population. The differences were more pronounced for males than for females and more for group than for individual activity. The genetic control of this behavioural trait was confirmed by breeding tests. Pure-bred offspring from wild-trapped voles within each area did not deviate from the performance of their parents. The hybrid offspring had intermediate test values. An association between behaviour and population density phase is indicated for the cycling population, but a full cycle has not yet been followed.

Minocycline affects cocaine sensitization in mice

Growing evidence has pointed to an interaction between the tetracycline antibiotic minocycline and drugs with abuse liability such as opioids and amphetamines. In this work, we tested the hypothesis that similar to its effects on methamphetamine-induced locomotor sensitization, minocycline may influence the behavioral effects of cocaine. Experiments were performed in male C57BL/6J mice using an automated system to measure locomotor activity. We found that 80 mg/kg minocycline significantly reduced locomotor activity when administered either alone or injected 30 min prior to cocaine, which increased locomotor activity. To investigate whether minocycline selectively affects the development of locomotor sensitization induced by four daily injections of 10 mg/kg cocaine, we sought a schedule of minocycline administration that does not per se affect locomotor activity. Thus, we selected 40 mg/kg minocycline administered 3 h prior to cocaine; minocycline did not affect cocaine-stimulated locomotor activity on the first day of administration but prevented the development of cocaine sensitization. We also tested whether minocycline would affect an already established cocaine sensitization. After establishing the sensitization effect by four daily injections, cocaine treatment was discontinued and mice were treated with minocycline daily (days 5–11) or on day 11 only. There was no effect of minocycline treatment on the response of cocaine-sensitized mice to the challenge dose of cocaine on day 11. The mechanisms by which minocycline interferes with the development of cocaine sensitization need to be characterized.

Phenotyping Food Entrainment: Motion Sensors and Telemetry Are Equivalent

Rats can anticipate a daily meal by entrainment of a circadian timekeeping mechanism that is anatomically separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nucleus. The dorsomedial nucleus of the hypothalamus (DMH) has been claimed to be critical for the expression of circadian rhythms of food anticipatory activity, but efforts to confirm this finding have so far failed. Failure to confirm that DMH ablation disrupts or eliminates food anticipatory rhythms has been attributed to the use of overhead motion sensors rather than telemetry to measure locomotor activity. To examine the relationship between motion sensor and telemetric measures of locomotor activity, transponders were implanted into the peritoneal cavity of adult male rats, and activity was recorded continuously by both telemetry and infrared motion sensors. Activity counts were approximately 4 fold higher as detected by telemetry, but normalized activity patterns were virtually identical for the two measures during ad-lib food access, 4 h/day food restriction and total food deprivation after food restriction. Overhead motion sensors and telemetry are equivalent measures of food anticipatory activity in rats. Telemetry is an effective tool for continuous recording of body temperature but has no advantages over infrared motion sensors for measuring food anticipatory activity rhythms.

Sex-specific 24-h acetylcholine release profile in the medial prefrontal cortex: Simultaneous measurement of spontaneous locomotor activity in behaving rats

The difference in visual object recognition by males and females suggests a sex-specific function in the medial prefrontal cortex (mPFC). In the present study, we performed an in vivo microdialysis study in three groups of rats (males, diestrous females, and proestrous females) to examine the potential sex difference in acetylcholine (ACh) release in the mPFC. The dialysate was automatically collected from the mPFC every 20 min for 24 h under freely moving conditions and the spontaneous locomotor activity was simultaneously monitored. Although ACh release in the mPFC during the dark phase was significantly greater than during the light phase in both sexes, the female rats consistently exhibited a significantly greater mean ACh release than the males. Spontaneous locomotor activity during the dark phase was also significantly greater than during the light phase in both sexes, but the females exhibited significantly greater spontaneous locomotor activity than the males. In addition, both sexes of rats were found to have significant positive correlations between ACh release and spontaneous locomotor activity, but females were found to have significantly greater correlation coefficients than males. Stereological methods were used to examine the number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis and the horizontal diagonal band of Broca. The number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis was also greater in females than males, suggesting a contribution to the higher ACh release in females. In contrast, no sex difference in the choline acetyltransferase immunoreactive cells was observed in the horizontal diagonal band of Broca. This is the first report to show a sex difference in the 24-h ACh release profile in the mPFC of behaving rats.

Genetic influences on drug‐induced psychomotor activation in mice

A number of processes are important in the development of substance dependence including initial sensitivity to the acute pharmacological effects of drugs/alcohol. The objectives of the present study were (1) to identify quantitative trait loci (QTLs) associated with the initial sensitivity to the effects of morphine in the A/J, C57BL/6J and AXB/BXA recombinant inbred strains of mice; (2) to identify potential commonalities in the chromosomal regions associated with morphine, cocaine and ethanol sensitivity using multiple-trait genetic analysis and (3) to determine whether there were interstrain differences in dopamine uptake and transporter binding. Initial sensitivity to morphine was determined by measuring locomotor activity in a computerized open-field apparatus following acute morphine administration (0, 10, 20 and 40 mg/kg). Significant differences in morphine-induced activation were observed across the panel of AXB/BXA mice. Genetic analysis found significant QTLs on chromosomes 5, 7, 11, 12, 15 and 17 close to loci previously mapped for cocaine-related behaviours and to parameters of dopaminergic functioning (uptake and receptor binding). Comparisons of the A/J vs. C57BL/6J progenitors found no strain differences for total dopamine uptake (V(max) or K(m)) in freshly prepared striatal synaptosomes from naive animals, and no differences in the IC(50) for the inhibition of dopamine uptake by cocaine. In addition, there were no differences in dopamine transporter density (B(max) or K(d)) measured using (3)H-GBR 12935 binding in synaptosomal membranes or via quantitative autoradiography. Multiple-trait analysis was conducted to examine the genetic interrelationships among morphine-, cocaine- and ethanol-induced activation in the AXB/BXA. Analysis yielded suggestive QTLs for the joint trait on chromosomes 5, 8, 13 and 15, as well as significant regions on chromosomes 11 (Pmv46, 11 cM, LOD = 7.39) and 12 (D12Mit110, 19 cM, LOD = 4.43) that may be common to all three drugs of abuse.

Ethnic Disparities in Blood Pressure Management in Patients With Hypertension After the Introduction of Pay for Performance

Little is known about the impact of pay-for-performance incentives on health care disparities. We examined ethnic disparities in the management of hypertension among patients with and without cardiovascular comorbidities after the implementation of a major pay-for-performance incentive scheme in UK primary care. We undertook a population-based, cross-sectional survey of medication prescriptions and blood pressure control among patients with hypertension using electronic medical records from 16 family practices in southwest London. Black patients with hypertension were significantly less likely to achieve an established treatment target for blood pressure control than white or South Asian patients (adjusted odds ratio, 0.86; 95% confidence interval, 0.74-0.99). The prevalence of cardiovascular comorbidities was higher among South Asian patients with hypertension than among their white or black counterparts (41.3% vs 28.5% vs 28.8%). The presence of 2 or more cardiovascular comorbidities was associated with significantly improved blood pressure control among white patients but not among black or South Asian patients (mean systolic blood pressure, -9.4 mm Hg, -0.6 mm Hg, and -1.8 mm Hg, respectively). South Asian patients with poorly controlled hypertension were prescribed fewer antihypertensive medications than their black or white peers (adjusted odds ratio, 0.66; 95% confidence interval, 0.46-0.96). Ethnic disparities in the management of hypertension have persisted in the United Kingdom despite major investment in quality improvement initiatives, including pay for performance. These disparities are particularly marked among patients with multiple cardiovascular conditions.

Anxiogenic-like effects induced by NMDA receptor activation are prevented by inhibition of neuronal nitric oxide synthase in the periaqueductal gray in mice

Glutamate-NMDA ( N-methyl- d-aspartate) receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction. We have recently demonstrated that the vigorous defensive-like behaviors (e.g. jumping and running) and antinociception induced by intra-PAG injection of N-methyl- d-aspartate (NMDA) were completely blocked by prior infusion of N ω-propyl- l-arginine (NPLA), a specific neuronal nitric oxide synthesis (nNOS) enzyme inhibitor, into the same midbrain structure. It remains unclear however, whether the inhibition of nNOS within the mouse PAG changes the anxiety-like behavior per se or the effects of the inhibition of nNOS depend on the suppression of downstream of glutamate-NMDA receptor activation. This study investigated whether intra-PAG infusion of NPLA ( i) attenuates anxiety in the elevated plus-maze (EPM) and ( ii) antagonizes the anxiogenic-like effects induced by intra-PAG injection of NMDA. Test sessions were videotaped and subsequently scored for conventional indices of anxiety (percentage of open arm entries and percentage of open arm time) and locomotor activity (closed arm entries). Results showed that intra-PAG infusions of NPLA (0.2, 0.4 or 0.8 nmol/0.1 μl) did not alter significantly any behavioral response in the EPM when compared to control group (Experiment 1). Intra-PAG infusion of NMDA (0 and 0.02 nmol/0.1 μl; a dose that does not provoke vigorous defensive behaviors per se in mice) significantly reduced open arm exploration, confirming an anxiogenic-like effect (Experiment 2). When injected into the PAG 10 min prior local NMDA injection (0.02 nmol/0.1 μl), NPLA (0.4 nmol/0.1 μl) was able to revert the anxiogenic-like effect of glutamate-NMDA receptor activation. Neither intra-PAG infusion of NMDA nor NPLA altered closed arm entries, a widely used measure of locomotor activity in the EPM. These results suggest that intra-PAG nitric oxide synthesis does not play a role on anxiety-like behavior elicited during EPM exposure; however its synthesis is important for the proaversive effects produced by activation of glutamate-NMDA receptors located within this limbic midbrain structure.

The absence of 5-HT1A receptors has minor effects on dopamine but not serotonin release evoked by MK-801 in mice prefrontal cortex

Non-competitive NMDA receptor antagonists markedly increase neuronal activity in medial prefrontal cortex (mPFC), an effect which partly underlies their schizomimetic actions. Projection pyramidal neurons and local GABAergic interneurons in mPFC express 5-HT(1A) receptors, whose activation modulates dopaminergic (DA) and serotonergic (5-HT) activity in midbrain and the cortical release of both monoamines. To examine whether the presence of 5-HT(1A) receptors can modulate the effect of NMDA receptor blockade with MK-801 (dizocilpine) on DA and 5-HT release in mouse mPFC. Brain microdialysis and locomotor activity measures in wild-type and 5-HT(1A) receptor knockout mice. Systemic MK-801 administration (0.125, 0.25, 0.50, and 1 mg/kg i.p.) induced a dose-dependent increase in mPFC 5-HT output, which was independent of the genotype. MK-801 increased DA output in a dose-dependent manner with a significant effect of genotype on low doses (0.125, 0.25 mg/kg). These differences were not paralleled by differences in gross locomotor activity. Overall, MK-801 increased more markedly DA than 5-HT output in both genotypes. Finally, the local perfusion of MK-801 in mPFC (30, 100, 300 muM) by reverse dialysis did not elevate dialysate DA or 5-HT concentrations in mPFC. 5-HT(1A) receptors partly modulate the increase in mPFC DA (but not 5-HT) release produced by NMDA receptor blockade. The lack of effect observed after the local MK-801 application suggests that the change in cortical monoamines is mainly driven by subcortical NMDA receptor blockade, without a significant involvement of PFC 5-HT(1A) receptors.

Intra-periaqueductal gray matter injections of midazolam fail to alter anxiety in plus-maze experienced mice

It is well known that prior experience to the elevated plus-maze increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effect of benzodiazepines evaluated during a subsequent exposure to the maze, a phenomenon known as “one-trial tolerance”. Centrally injected benzodiazepine drugs attenuate anxiety in some limbic structures, such as hypothalamus, amygdala and the midbrain periaqueductal gray (PAG). This study investigated the effects of intra-PAG infusions of midazolam (MDZ) in maze-naïve and maze-experienced mice. The antiaversive effects of MDZ (3.0 nmol and 30 nmol in 0.1 μl) were evaluated by prior injection of flumazenil (16 nmol/0.1 μl), a benzodiazepine receptor antagonist, into the same midbrain site. Test videotapes were scored for conventional measures of anxiety and locomotor activity, as well as a range of ethological measures related to risk assessment. In maze-naïve mice, intra-PAG infusions of MDZ increased % open arm entries (3.0 nmol) and % open arm time (3.0 and 30 nmol). These effects were observed in the absence of significant changes in locomotor activity, indicating a selective anxiolytic-like effect of MDZ. The antiaversive effects of MDZ were completely blocked by prior injection of flumazenil which in turn did not alter any other behavioral measure. In maze-experienced mice, intra-PAG infusion of MDZ did not modify any behavioral measure. Taken together, present results corroborate previous studies demonstrating that GABA/benzodiazepine receptor complex located within the PAG plays a role on anxiety modulation in maze-naïve mice as well as indicate its involvement in the OTT phenomenon.

Increased Lipid Oxidation Heralds Diabetes Onset in DR.lyp/lyp Rats

The BB rat model of type 1 diabetes exhibits altered body weight gain and body temperature regulation prior to hyperglycemia onset, implying the existence of as yet unidentified biomarkers of autoimmune processes that destroy pancreatic beta cells. To investigate this hypothesis, we compared the metabolic profile of diabetes-resistant DR.lyp/+ rats and their diabetes-prone, congenic DR.lyp/lyp littermates in the days leading up to diabetes onset. Except for the Gimap5 mutation on chromosome 4, congenic DR.lyp/lyp rats are genetically identical to DR.lyp/+ littermates. They invariably develop hyperglycemia at 46-81 days of age, whereas DR.lyp/+ rats do not develop diabetes. In addition to daily food intake and body weight, indirect calorimetry was performed continuously on male DR.lyp/lyp and DR.lyp/+ rats (n=6/group) for 6-18 days to measure locomotor activity, VO (2), VCO (2) and RQ. DR.lyp/lyp rats exhibited a progressive decrease of RQ compared to DR.lyp/+ rats 0.005+/-0.001 units/day (p<0.005). Limiting the analysis to the six days prior to diabetes onset revealed a larger decrease of 0.007+/-0.002 units/day (p<0.001) in DR.lyp/lyp animals, whereas RQ of the DR.lyp/+ rats remained unchanged. This metabolic change occurred prior to hyperglycemia onset and was not associated with changes of any other parameter. Diabetes onset in DR.lyp/lyp rats is heralded by a progressive shift towards lipid oxidation relative to carbohydrate metabolism.

Gemvid, an open source, modular, automated activity recording system for rats using digital video

Measurement of locomotor activity is a valuable tool for analysing factors influencing behaviour and for investigating brain and sleep functions. Several methods have been described in the literature for measuring the amount animal movement but most are flawed or expensive. Here, we describe an open source, modular, low-cost, user-friendly, highly sensitive, non-invasive system that records all the movements of a rat in its cage. Our activity monitoring system quantifies overall free movements of rodents without any markers, using a commercially available CCTV and a newly designed motion detection software developed on a GNU/Linux-operating computer. The operating principle is that the amount of overall movement of an object can be expressed by the difference in total area occupied by the object in two consecutive picture frames. The application is based on software modules that allow the system to be used in highthroughput work-flow. Documentation, example files, source code and binary files can be freely downloaded on the web. In a series of experiments with objects of pre-defined oscillation frequencies and movements, we documented the sensitivity, reproductibility and stability of our system. We also compared data obtained with our system and data obtained with an Actiwatch device. Finally, to validate the system, results obtained from the automated observation of 6 rats during 7 days in a regular light cycle are presented and are accompanied by a stability test. The validity of this system is further demonstrated through the observation of 2 rats in constant dark conditions that displayed the expected free running of their circadian rhythm. In conclusion, the present study describes a system that relies on video frame differences to automatically quantify overall free movements of a rodent without any markers. It allows the monitoring of rats in their own environment for an extended period of time. By using a low-cost, open source hardware/software solution, laboratories can greatly simplify their data acquisition and analysis pipelines and improve their workload.