Locomotor Activity In Response Research Articles

Cognitive and behavioral effects of whole brain conventional or high dose rate (FLASH) proton irradiation in a neonatal Sprague Dawley rat model.

Recent studies suggest that ultra-high dose rates of proton radiation (>40 Gy/s; FLASH) confer less toxicity to exposed healthy tissue and reduce cognitive decline compared with conventional radiation dose rates (~1 Gy/s), but further preclinical data are required to demonstrate this sparing effect. In this study, postnatal day 11 (P11) rats were treated with whole brain irradiation with protons at a total dose of 0, 5, or 8 Gy, comparing a conventional dose rate of 1 Gy/s vs. a FLASH dose rate of 100 Gy/s. Beginning on P64, rats were tested for locomotor activity, acoustic and tactile startle responses (ASR, TSR) with or without prepulses, novel object recognition (NOR; 4-object version), striatal dependent egocentric learning ([configuration A] Cincinnati water maze (CWM-A)), prefrontal dependent working memory (radial water maze (RWM)), hippocampal dependent spatial learning (Morris water maze (MWM)), amygdala dependent conditioned freezing, and the mirror image CWM [configuration B (CWM-B)]. All groups had deficits in the CWM-A procedure. Weight reductions, decreased center ambulation in the open-field, increased latency on day-1 of RWM, and deficits in CWM-B were observed in all irradiated groups, except the 5 Gy FLASH group. ASR and TSR were reduced in the 8 Gy FLASH group and day-2 latencies in the RWM were increased in the FLASH groups compared with controls. There were no effects on prepulse trials of ASR or TSR, NOR, MWM, or conditioned freezing. The results suggest striatal and prefrontal cortex are sensitive regions at P11 to proton irradiation, with reduced toxicity from FLASH at 5 Gy.

Blunted Amphetamine-induced Reinforcing Behaviors and Transporter Downregulation in Knock-in Mice Carrying Alanine Mutations at Threonine-258 and Serine-259 of Norepinephrine Transporter

Altered amine transporter function, phosphorylation, and association with interacting proteins are evident in animals with a history of psychostimulant exposure. Our previous studies have shown that the Thr258/Ser259 motif in the norepinephrine transporter (NET) is involved in amphetamine (AMPH)-mediated NET regulation and behavior. However, the neurobiological consequences of in vivo Thr258/Ser259-dependent NET regulation in an intact animal model are unclear. Therefore, we generated a viable construct-valid NET-Thr258Ala/Ser259Ala (NET-T258A/S259A) mouse model using CRISPR/Cas9 technology by replacing Thr258/Ser259 motif with Ala258/Ala259 motif. NET-T258A/S259A mice have a birth rate consistent with Mendelian inheritance ratios. Both male and female homozygous NET-T258A/S259A mice are viable, display normal growth and general health, and exhibit normal body weight (sex-dependent) and total activity in the open field similar to their wild-type (WT) littermates. NET-T258A/S259A mice showed reduced NET function in the prefrontal cortex (PFC) compared to WT mice while NET function in the nucleus accumbens (NAc) remained unchanged. Compared to respective WT counterparts, NET-T258A/S259A males but not females showed significantly reduced locomotor activation in response to acute AMPH administration and significantly reduced AMPH-induced conditioned place preference (CPP). When tested in the males only, acute AMPH administration inhibited NET function and surface expression in the WT NAc but not in the NET-T258A/S259A NAc while AMPH administration inhibited DAT function and surface expression in the NAc of both WT and NET-T258A/S259A mice. Collectively, our findings reveal that the mice carrying the T258A/S259A mutation in NET gene display brain region-specific differences in NET functional expression and blunted response to AMPH.

Prelimbic medial prefrontal cortex has bidirectional control over the expression of behavioral sensitization to 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) depending on the context of drug administration

Behavioral sensitization to MDMA is observed in the vast majority of rats if tested in the same environment in which previous MDMA exposure occurred, but not if tested in a novel, unpaired context. Previous studies have revealed a critical role for the prelimbic region of medial prefrontal cortex (PL) in the expression of sensitization to MDMA, but these studies assessed sensitization only in MDMA-paired environments. Given that PL activity can both facilitate and suppress behavior depending on context, we tested the hypothesis that PL has bidirectional control over the expression of locomotor sensitization to MDMA depending on the context of drug administration. Rats were treated with either saline or MDMA (5.0 mg/kg) twice daily for 5 days, in either their home cages (unpaired groups) or the activity monitors that were used for tests of sensitization on challenge days (paired groups). Prior to MDMA challenge injections (2.5 mg/kg; at ∼ 2 weeks of withdrawal), rats received bilateral PL microinjections of either lidocaine (100 μg/0.5 μl/side) or physiological saline (0.5 μl/side). Locomotor activity in response to MDMA challenge was unaffected by PL inactivation in saline pretreated rats. However, PL inactivation caused a decrease in locomotion to the challenge injection in MDMA/paired rats and an increase in locomotion in MDMA/unpaired rats. These results establish a novel role for PL in suppressing the expression of behavioral sensitization when subjects are challenged in a drug-unpaired context, adding to the literature implicating PL activity in both the expression and inhibition of other drug-related behaviors.

The opposing chloride cotransporters KCC and NKCC control locomotor activity in constant light and during long days

Cation chloride cotransporters (CCCs) regulate intracellular chloride ion concentration ([Cl-]i) within neurons, which can reverse the direction of the neuronal response to the neurotransmitter GABA.1 Na+ K+ Cl- (NKCC) and K+ Cl- (KCC) cotransporters transport Cl- into or out of the cell, respectively. When NKCC activity dominates, the resulting high [Cl-]i can lead to an excitatory and depolarizing response of the neuron upon GABAA receptor opening, while KCC dominance has the opposite effect.1 This inhibitory-to-excitatory GABA switch has been linked to seasonal adaption of circadian clock function to changing day length,2-4 and its dysregulation is associated with neurodevelopmental disorders such as epilepsy.5-8 In Drosophila melanogaster, constant light normally disrupts circadian clock function and leads to arrhythmic behavior.9 Here, we demonstrate a function for CCCs in regulating Drosophila locomotor activity and GABA responses in circadian clock neurons because alteration of CCC expression in circadian clock neurons elicits rhythmic behavior in constant light. We observed the same effects after downregulation of the Wnk and Fray kinases, which modulate CCC activity in a [Cl-]i-dependent manner. Patch-clamp recordings from the large LNv clock neurons show that downregulation of KCC results in a more positive GABA reversal potential, while KCC overexpression has the opposite effect. Finally, KCC and NKCC downregulation reduces or increases morning behavioral activity during long photoperiods, respectively. In summary, our results support a model in which the regulation of [Cl-]i by a KCC/NKCC/Wnk/Fray feedback loop determines the response of clock neurons to GABA, which is important for adjusting behavioral activity to constant light and long-day conditions.

The Effect of Melatonin and Exercise on Social Isolation-Related Behavioral Changes in Aged Rats.

Social isolation (SI) is well established as an environmental factor that negatively influences different behavioral parameters, including cognitive function, anxiety, and social interaction, depending on the age of isolation. Aging is a physiological process that is associated with changes in cognitive function, locomotor activity, anxiety and emotional responses. Few studies have investigated the effect of SI in senescence, or possible interventions. In the current study, we investigated the possible complementary effects of melatonin (MLT) and exercise (Ex) in improving SI-related behavioral changes in aged rats. Forty aged Wistar rats (24 months old) were randomly divided into five groups (n = 8 per group): Control (group housing), SI (individual housing for 7 weeks), SI + MLT (SI rats treated with 0.4 mg MLT/ml in drinking water), SI + Ex (SI rats treated with 60 min of swimming), and SI + MLT + Ex (SI rats treated with both MLT and Ex). Different behavioral tasks were conducted in the following sequence: open field test, elevated plus maze test, sucrose preference test, Y maze test, and Morris water maze test. Locomotor activities measured by total distance moved and velocity revealed that SI + Ex (P = 0.0038; P = 0.0015) and SI + MLT + Ex (P = 0.0001; P = 0.0003) significantly improved the locomotor activity compared with SI rats but SI + MLT (P = 0.0599; P = 0.0627) rats showed no significant change. Anxiety index score was significantly improved in SI + MLT + Ex (P = 0.0256) compared with SI rats while SI + MLT (P > 0.9999) and SI + Ex (P = 0.2943) rats showed no significant change. Moreover, latency to reach the platform in Morris water maze was significantly reduced at day 5 in SI + MLT + Ex (P = 0.0457) compared with SI rats but no change was detected in SI + MLT (P = 0.7314) or SI + Ex (P = 0.1676) groups. In conclusion, this study supports the possible potential of MLT in combination with Ex in improving physical activity, anxiety, and cognitive functions in aging population.

Impact of acute and chronic nicotine administration on midbrain dopaminergic neuron activity and related behaviours in TRPV1 knock-out juvenile mice.

The addictive properties of nicotine, the main alkaloid in tobacco and tobacco-derived products, largely depend on its action on the activity of midbrain dopamine (DA) neurons. The transient receptor potential vanilloid 1 (TRPV1) channel has also been examined as an emerging contributor to addiction-related symptoms due to its ability to modulate midbrain neurons. Thus, the objective of our study was to explore the role of TRPV1 receptors (TRPV1Rs) on nicotine-induced behaviours and associated response of DA neuron activity. Both wild type juvenile mice and juvenile mice with invalidation of the TRPV1R gene were exposed to acute or chronic nicotine 0.3mg/kg administration. We analysed locomotor activity in response to the drug. In addition, we performed cell-attached and whole-cell recordings from ventral tegmental area (VTA) neurons after nicotine exposure. Our results showed that the genetic deletion of TRPV1Rs reduced nicotine-induced locomotor sensitization. In addition, it provided evidence in support of TRPV1Rs being regulators of inhibitory synaptic transmission in the VTA. However, TRPV1Rs did not seem to modulate either nicotine-induced conditioning place preference or nicotine-evoked electrical activity of DA neurons. In conclusion, TRPV1Rs modulate nicotine-induced psychomotor sensitization in mice independently of a control on VTA DA neuron activity. Thus, TRPV1R control may depend on another key player of the mesolimbic circuit.

Rrn3 gene knockout affects ethanol-induced locomotion in adult heterozygous zebrafish.

Genome-wide analysis has identified the transcription factor, RRN3 (or TIF-1A), on human chromosome 16p13.11 as a candidate gene associated with mental disorders. Both genetic and biochemical experiments have demonstrated that RRN3 plays a major role in the transcriptional regulation of ribosomal DNA and cell growth. Previous research has suggested that loss of RRN3 from mature neurons reproduces the chronic nature of neurodegenerative processes. Here, we report the first generation and characterization of rrn3 mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique. Homozygous knockout zebrafish exhibited morphological changes, such as pericardial oedema and deformed heads, and died at the larval stage of embryonic development. Behaviourally, the locomotion and shoaling behaviour of adult rrn3+/- zebrafish was not significantly different compared with rrn3+/+ zebrafish. Notably, rrn3+/- zebrafish demonstrated abnormal locomotor activity in response to ethanol. We found decreased norepinephrine expression in the brains of rrn3+/- zebrafish when treated with ethanol. In summary, our results indicated that rrn3 was closely associated with early embryonic development in zebrafish. Furthermore, behavioural and neurochemical research revealed the importance of genetic differences in drug sensitivity. The results suggest that caution should be taken when treating RRN3 heterozygous patients.

Conditioned Lick Suppression: Assessing Contextual, Cued, and Context-cue Compound Fear Responses Independently of Locomotor Activity in Mice.

Pavlovian fear conditioning is a widely used procedure to assess learning and memory processes that has also been extensively used as a model of post-traumatic stress disorder (PTSD). Freezing, the absence of movement except for respiratory-related movements, is commonly used as a measure of fear response in non-human animals. However, this measure of fear responses can be affected by a different baseline of locomotor activity between groups and/or conditions. Moreover, fear conditioning procedures are usually restricted to a single conditioned stimulus (e.g., a tone cue, the context, etc.) and thus do not depict the complexity of real-life situations where traumatic memories are composed of a complex set of stimuli associated with the same aversive event. To overcome this issue, we use a conditioned lick suppression paradigm where water-deprived mice are presented with a single conditioned stimulus (CS, a tone cue or the context) previously paired with an unconditioned stimulus (US, a foot shock) while consuming water. We use the ratio of number of licks before and during the CS presentation as a fear measure, thereby neutralizing the potential effect of locomotor activity in fear responses. We further implemented the conditioned lick suppression ratio to assess the effect of cue competition using a compound of contextual and tone cue conditioned stimuli that were extinguished separately. This paradigm should prove useful in assessing potential therapeutics and/or behavioral therapies in PTSD, while neutralizing potential confounding effects between locomotor activity and fear responses on one side, and by considering potential cue-competition effects on the other side. This protocol was validated in: Transl Psychiatry (2022), DOI: 10.1038/s41398-022-01815-2 Graphical abstract Schematic representation of the compound context-cue condition lick suppression procedure. Illustration reproduced from Bouchekioua et al. (2022).

Effects of simulated environmental discharges of the salmon lice pesticides deltamethrin and azamethiphos on the swimming behaviour and survival of adult Northern shrimp (Pandalus borealis).

Swimming behaviour was investigated in adult egg-carrying northern shrimp (Pandalus borealis) exposed to dilute concentrations of the pesticides Alpha Max® (active ingredient deltamethrin) and Salmosan® (active ingredient azamethiphos) used to control parasitic copepods in salmon aquaculture. These treatments are applied topically within fish nets or well boats. Following a short treatment period, the pesticides are directly discharged to sea, exposing non-target organisms such as P. borealis to diluted concentrations of these chemicals. Locomotor activity was measured continuously in individual shrimp over several days within which they were exposed to treatments of diluted AlphaMax® or Salmosan®. Dilutions were based on modelling and dispersion studies from the literature and were considered environmentally realistic for greater than 1km from point of discharge. 24h continuous flow treatments were delivered within a 3.5-day monitoring period to observe the timeline of events following the release of treatment water, addressing questions of temporal responses in locomotor activity, recognising key time points of significant events and assessing the survival capacity of the shrimp. Exposure of shrimp to 1ng l-1 deltamethrin triggered an immediate increase in swimming activity which reduced in intensity over the following 22h leaving all shrimp either moribund or dead. A further exposure trial exposing shrimp to 0.2ng l-1 deltamethrin (nominal) showed an increase in activity at the start of exposure that continued throughout the 24h delivery, returning to previous levels by the end of the 3.5-day monitoring period. All these shrimps survived for at least four weeks after exposure, putting the threshold concentration of deltamethrin leading to immobility or death in adult P. borealis within this study at greater than 0.2ng l-1 (nominal) and less than 1ng l-1 (measured). Exposure of P. borealis to azamethiphos at 30ng l-1 induced several periods of significantly increased activity within the first 10h of exposure and an extended period of reduced activity during post exposure, though no morbidity was observed with this treatment. No significant increase in activity or morbidity was observed in shrimp during a water vehicle control assessment. Shrimps exposed to a combination of 30ng l-1 azamethiphos and 1ng l-1 deltamethrin broadly followed the response pattern shown by shrimp exposed to 1ng l-1 deltamethrin alone. Pesticide residues were not detected in post exposure tissue analyses for either chemical. The potential ecological significance of increased swimming activity at the start of pesticide exposures is discussed.

Paracetamol (Acetaminophen) and the Developing Brain.

Paracetamol is commonly used to treat fever and pain in pregnant women, but there are growing concerns that this may cause attention deficit hyperactivity disorder and autism spectrum disorder in the offspring. A growing number of epidemiological studies suggests that relative risks for these disorders increase by an average of about 25% following intrauterine paracetamol exposure. The data analyzed point to a dose–effect relationship but cannot fully account for unmeasured confounders, notably indication and genetic transmission. Only few experimental investigations have addressed this issue. Altered behavior has been demonstrated in offspring of paracetamol-gavaged pregnant rats, and paracetamol given at or prior to day 10 of life to newborn mice resulted in altered locomotor activity in response to a novel home environment in adulthood and blunted the analgesic effect of paracetamol given to adult animals. The molecular mechanisms that might mediate these effects are unknown. Paracetamol has diverse pharmacologic actions. It reduces prostaglandin formation via competitive inhibition of the peroxidase moiety of prostaglandin H2 synthase, while its metabolite N-arachidonoyl-phenolamine activates transient vanilloid-subtype 1 receptors and interferes with cannabinoid receptor signaling. The metabolite N-acetyl-p-benzo-quinone-imine, which is pivotal for liver damage after overdosing, exerts oxidative stress and depletes glutathione in the brain already at dosages below the hepatic toxicity threshold. Given the widespread use of paracetamol during pregnancy and the lack of safe alternatives, its impact on the developing brain deserves further investigation.

MK-801-induced behavioral and dopaminergic responses in the shell part of the nucleus accumbens in adult male rats are disrupted after neonatal blockade of the ventral subiculum

The present study was conducted in the context of animal modeling of schizophrenia. It investigated in adult male rats, after transient neonatal blockade of the ventral subiculum (VSub), the impact of a very specific non-competitive antagonist of NMDA receptors (MK-801) on locomotor activity and dopaminergic (DAergic) responses in the dorsomedial shell part of the nucleus accumbens (Nacc), a striatal subregion described as the common target region for antipsychotics.The functional neonatal inactivation of the VSub was achieved by local microinjection of tetrodotoxin (TTX) at postnatal day 8 (PND8). Control pups were microinjected with the solvent phosphate buffered saline (PBS). Locomotor responses and DAergic variations in the dorsomedial shell part of the Nacc were measured simultaneously using in vivo voltammetry in awake, freely moving male animals after sc administration of MK-801. The following results were obtained: 1) a dose-dependent increase in locomotor activity in PBS and TTX animals, greater in TTX rats/PBS rats; and 2) divergent DAergic responses for PBS and TTX animals. A decrease in DA levels with a return to around basal values was observed in PBS animals. An increase in DA levels was obtained in TTX animals. The present data suggest that neonatal blockade of the VSub results in disruption in NMDA glutamatergic transmission, causing a disturbance in DA release in the dorsomedial shell in adults male rats. In the context of animal modeling of schizophrenia using the same approach it would be interesting to investigate possible changes in postsynaptic NMDA receptors-related proteins in the dorsomedial shell region in the Nacc.

Effects of fentanyl on acute locomotor activity, behavioral sensitization, and contextual reward in female and male rats

BackgroundAlthough fentanyl has gained widespread prominence, there remains a lack of knowledge on this opioid synthetic agonist, particularly related to sex effects. Therefore, we conducted behavioral tests in female and male rats to measure drug abuse-related responses to fentanyl hypothesizing sex-specific responses. MethodsUsing female and male rats, we measured the effects of acute or repeated administration of fentanyl (20 μg/kg) on locomotor activity (LMA) and behavioral sensitization in an open field test. We further measured contextual-reward and associated locomotor activity during training in a conditioned place preference (CPP) paradigm using a low (4 μg/kg) or high (16 μg/kg) dose of fentanyl. Vaginal lavage samples were collected from female rats in the CPP study, and the estrous phase was determined based on the cytological characterization. ResultsFemale, but not male, rats showed elevated LMA in response to acute fentanyl and behavioral sensitization to repeated administration of fentanyl. Fentanyl produced significant CPP in both sexes, but it was more potent in males. Finally, our secondary investigation of the estrous cycle on fentanyl-CPP suggests that non-estrus phases, likely reflecting high estradiol, may predict the degree of fentanyl preference in females. ConclusionsFentanyl was more potent and/or effective to produce LMA and LMA sensitization in females but more potent to produce CPP in males. Furthermore, the role of sex in fentanyl responses varied across endpoints, and sex differences in LMA were not predictive of sex differences in CPP.

THE EFFECTS OF SYSTOLIC ARTERIAL PRESSURE ON LOCOMOTOR ACTIVITY IN CONGENIC RATS DERIVED FROM STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR KYOTO RATS

Objective: The systolic arterial pressure (SAP) levels of congenic rats were reported to be intermediate between those of stroke-prone spontaneously hypertensive (SHRSP) rats and Wistar Kyoto (WKY) rats, and the congenic rats were reported to exhibit higher locomotor activity than SHRSP and WKY rats. Locomotor activity in the early morning was higher in the congenic rats than in the other two strains. However, no study on the relationship between SAP and locomotor activity in congenic rats has been performed. Therefore, we aimed to examine this topic. Design and method: We used 10 mature male congenic rats and age- and gender-matched SHRSP and WKY rats (n = 10 each) as the controls. We measured the SAP and locomotor activity of the rats telemetrically. We estimated best-fit curves of locomotor activity using the maximal entropy method. Results: The congenic rats exhibited the highest locomotor activity counts (congenic rats vs. SHRSP rats vs. WKY rats: 58 (23, 89) vs. 18 (4, 40) vs. 4 (1, 8) counts/10 seconds (median, Q1, Q3), P = 0.0010). The congenic rats also exhibited SAP levels that were intermediate between those of the SHRSP and WKY rats (congenic rats vs. SHRSP rats vs. WKY rats: 194 ± 7 vs. 229 ± 7 vs. 117 ± 4 mmHg (mean ± SD, P = 0.0098). The strongest correlation between locomotor activity and SAP was seen in the congenic rats (Y = -1851.3 + 9.87X, rS = 0.592, P = 0.00001). The ratio of the increase in locomotor activity to the increase in SAP was highest in the congenic rats (congenic rats vs. SHRSP rats vs. WKY rats: 7.05 (4.92, 10.20) vs. 0.04 (0.87, 0.88) vs. 0.11 (3.46, 3.55)(median, Q1, Q3); SHRSP rats vs. congenic rats: P < 0.01; SHRSP rats vs. WKY rats: n.s.; congenic rats vs. WKY rats: P < 0.05). Conclusions: Among these three rat strains, the response of locomotor activity to increases in SAP was strongest in the congenic rats.

Habenula GPR139 is associated with fear learning in the zebrafish

G-protein coupled receptor 139 (GPR139) is an evolutionarily conserved orphan receptor, predominantly expressing in the habenula of vertebrate species. The habenula has recently been implicated in aversive response and its associated learning. Here, we tested the hypothesis that GPR139 signalling in the habenula may play a role in fear learning in the zebrafish. We examined the effect of intraperitoneal injections of a human GPR139-selective agonist (JNJ-63533054) on alarm substance-induced fear learning using conditioned place avoidance paradigm, where an aversive stimulus is paired with one compartment, while its absence is associated with the other compartment of the apparatus. The results indicate that fish treated with 1 µg/g body weight of GPR139 agonist displayed no difference in locomotor activity and alarm substance-induced fear response. However, avoidance to fear-conditioned compartment was diminished, which suggests that the agonist blocks the consolidation of contextual fear memory. On the other hand, fish treated with 0.1 µg/g body weight of GPR139 agonist spent a significantly longer time in the unconditioned neutral compartment as compared to the conditioned (punished and unpunished) compartments. These results suggest that activation of GPR139 signalling in the habenula may be involved in fear learning and the decision-making process in the zebrafish.

Behavioral phenotyping of mice lacking the deubiquitinase USP2

Ubiquitin specific peptidase 2 (USP2) is a deubiquitinating enzyme expressed almost ubiquitously in the body, including in multiple brain regions. We previously showed that mice lacking USP2 present altered locomotor activity rhythms and response of the clock to light. However, the possible implication of USP2 in regulating other behaviors has yet to be tested. To address this, we ran a battery of behavioral tests on Usp2 KO mice. Firstly, we confirmed our prior findings of increased daily activity and reduced activity fragmentation in Usp2 KO mice. Further, mice lacking USP2 showed impaired motor coordination and equilibrium, a decrease in anxiety-like behavior, a deficit in working memory and in sensorimotor gating. On the other hand, no effects of Usp2 gene deletion were found on spatial memory. Hence, our data uncover the implication of USP2 in different behaviors and expands the range of the known functions of this deubiquitinase.

Locomotor activity and growth response of glass eel Anguilla marmorata exposed to different salinity levels

Temperate eels are well known for partial migration where contingents may remain settled in marine habitats or move between seawater and brackish and freshwater habitats during their sub-adult life. This behaviour is less described in tropical Anguillid eels, particularly as it relates to salinity preference, habitat selection, and growth. In this study, glass eels Anguilla marmorata were collected from an estuary near the Cagayan River, northern Philippines, and observed for their behaviour and growth response in freshwater, brackish water, and seawater. A. marmorata glass eels spent most of their time in freshwater and brackish water and the least amount of time in seawater throughout the 30-min trial. Some individuals showed switching behaviour between salinity choices, but freshwater was the final selection. Growth-in-length was moderately and significantly lower for seawater-reared glass eels than those reared in freshwater and brackish water. Glass eels reared in freshwater had the highest survival, followed by those reared in brackish water and seawater. Habitat choice, growth, and survival trials all indicated that A. marmorata glass eels found in the Cagayan River have a major preference for freshwater and brackish water over seawater. These findings raise concerns with regard to the increased fishing pressure of eels, water pollution, and quarrying which is concentrated in freshwater habitats.

Reducing l-lactate release from hippocampal astrocytes by intracellular oxidation increases novelty induced activity in mice.

Astrocytes are in control of metabolic homeostasis in the brain and support and modulate neuronal function in various ways. Astrocyte‐derived l‐lactate (lactate) is thought to play a dual role as a metabolic and a signaling molecule in inter‐cellular communication. The biological significance of lactate release from astrocytes is poorly understood, largely because the tools to manipulate lactate levels in vivo are limited. We therefore developed new viral vectors for astrocyte‐specific expression of a mammalianized version of lactate oxidase (LOx) from Aerococcus viridans. LOx expression in astrocytes in vitro reduced their intracellular lactate levels as well as the release of lactate to the extracellular space. Selective expression of LOx in astrocytes of the dorsal hippocampus in mice resulted in increased locomotor activity in response to novel stimuli. Our findings suggest that a localized decreased intracellular lactate pool in hippocampal astrocytes could contribute to greater responsiveness to environmental novelty. We expect that use of this molecular tool to chronically limit astrocytic lactate release will significantly facilitate future studies into the roles and mechanisms of intercellular lactate communication in the brain.

Influence of acute exposure to a low dose of systemic insecticide fipronil on locomotor activity and emotional behavior in adult male mice.

Fipronil (FPN) is a systemic insecticide that antagonizes the gamma-aminobutyric acid type A (GABAA) receptors in insects. Recently, adverse effects of FPN on mammals have been reported, but most of those were caused by high doses of FPN and additives in the products. We investigated the effects of low-dose pure FPN on the emotional behavior of mice. Nine-week-old male mice conducted behavioral tests 24 hr after FPN administration by gavage at doses of 0.05 or 5 mg/kg based on the no-observed-effect level (NOEL), showed a significant increase in locomotor activity and dose-dependent responses on the time they spent in the central zone in the open field test. Pure FPN below the NOEL dose may affect the emotional behavior of mice.

The effects of ovariectomy on the behavioral and physiological responses to constant light in C57BL6/J Mice

ABSTRACT Circadian disruptions, including exposure to constant light, are known to produce behavioral and physiological issues. However, sex differences exist in how those problems manifest, as males tend to have increased susceptibility to the negative consequences of circadian disruption. As gonadal hormones play a role in circadian timekeeping, we decided to investigate whether ovariectomized C57BL6/J mice would exhibit increased behavioral and physiological sensitivity to constant light compared to female mice with intact estrogen circulation. Mice, half of which underwent an ovariectomy and the other half received sham surgery, were then placed in either constant light or a 12:12 light-dark cycle. After six weeks of photoperiod exposure, we measured their circadian locomotor activity, anxiety-like behaviors and physiological responses. Mice which underwent ovariectomy and placed into constant light experienced altered glucose levels and reduced robustness of the circadian rhythm, with some becoming arrhythmic, compared to sham surgery animals in constant light. Additionally, ovariectomy led to delayed circadian activity onsets and reduced both home-cage and novelty-induced activity. Meanwhile, constant light produced increases to ambulatory activity in the behavioral assays and reduced circadian home-cage activity. These results indicate that removal of the ovaries can mediate the circadian, behavioral, and physiological responses to continuous light.

Selective activation of D1 dopamine receptors exerts antidepressant-like activity in rats.

Major depressive disorder is a common illness that severely decreases psychosocial functioning. Due to the major limitations of current treatments including response failure, it is crucial to develop better therapy strategies. Evidence suggests that dopamine dysregulation might play a major role in major depressive disorder physiopathology. This study investigates whether the dopamine D1 receptor agonist A77636 modulates antidepressant-like activity in rats. Rats were injected with an acute single dose of A77636 (0.75, 1.5 or 3 mg/kg), a potent and selective dopamine D1-like receptor agonist. Their locomotor activity, social interactions and behavioural response to the forced swim test were analysed 30 min after the injection. During the forced swim test, the D1 agonist dose dependently reduced the immobility while the time of bursting was increased. Social interactions were significantly increased in the animals exposed to 3 mg/kg of A77636 whereas no significant changes were measured in general motor activity. The present results provide evidence that pharmacological modulation of D1 receptor by the selective agonist A77636 induces antidepressant-like effects in rats, which encourages further studies regarding D1-specific modulation in major depressive disorder treatment.