Locomotor Activity In Mice Research Articles

Combined Effects of Arsenic and Bisphenol-A on Locomotor Activity and Oxidative Stress Mediated Neurotoxicity in Mice.

Bisphenol A (BPA) is a monomer of plastic that can leach into water from scratched containers when used for an extended period. Arsenic (As) is an environmental toxicant, and people are exposed to both arsenic and BPA through drinking water and through scratched plastic containers used in contaminated areas. However, the combined effects of As and BPA on locomotor performance and neurobehavioral changes are yet to be investigated. Thus, this study was designed to assess the combined effect of As and BPA on locomotor activity and neurotoxicity through a mouse model. The neurobehavioral changes in experimental mice were evaluated using the different maze tests. Mice exposed to As or BPA exhibited higher anxiety-like behavior, decreased locomotor activity, and impaired learning and memory including social interaction compared with control mice. However, As + BPA-exposed mice showed a significantly reduced anxiety-like behavior, improved learning and memory including locomotor activity, and social interaction compared to individual As-exposed mice. Furthermore, mice exposed to As or BPA showed lower levels of antioxidant and cholinesterase enzymes activity, nuclear factor erythroid-2-related factor-2 (Nrf2), heme-oxygenase-1 (HO-1), and interleukin-10 (IL-10) in the brain and higher levels of interleukin-6 (IL-6) in the brain and lactate dehydrogenase (LDH) in the serum compared to control mice. However, combined exposure augmented antioxidant and cholinesterase enzymes activity, Nrf2, HO-1, IL-10 levels in the brain and reduced serum LDH activity and IL-6 in the brain compared to As exposure. Therefore, this study suggests that As and BPA may have antagonistic effects, and BPA could attenuate the As-induced neurobehavioral and biochemical changes in co-exposed mice.

A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity

A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity

Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice

Intra-telencephalic neurons are a crucial class of cortical principal neurons that heavily innervate the striatum and cortical areas bilaterally. Their extensive cortico-cortical and cortico-striatal connectivity enables sensorimotor integration within the telencephalon, but their role in motor control remains poorly understood. Here, we used a chemogenetic approach to explore the role of intra-telencephalic neurons in spontaneous locomotor activity. Bilateral chemogenetic activation of intra-telencephalic Tlx3+ neurons in the mouse motor cortex reduced spontaneous locomotor activity in the open field, increasing states of freezing and immobility. This anti-motor effect was achieved in separate experiments with either administration of two chemogenetic actuators, clozapine N-oxide and deschloroclozapine. A systemic administration of the dopamine D1 receptor agonist SKF82958 reversed the chemogenetic effect on locomotor activity. Selective chemogenetic stimulation of intra-telencephalic neurons was confirmed through post-mortem c-Fos quantification in cortical layer 5 Tlx3+ neurons. The results establish a causal link between the activity level of intra-telencephalic neurons in the motor cortex, spontaneous locomotor activity in the open field, and the dopamine system. The findings are compatible with the hypothesis that intra-telencephalic neurons regulate spontaneous motor behavior via its bilateral cortico-striatal projections.

Synergistic Anxiolytic Effects of Linalool and Sesamol Co-Treatment on Swiss Albino Mice: A Potential GABAergic Intervention.

Sesamol (SES) and linalool (LIN) are aromatic compounds that have neuroprotective effects. The main purpose of this study is to evaluate the anxiolytic activity of LIN and SES co-treatment on Swiss albino mice and analyze its possible mechanism through in silico study. In this sense, the mice were given the gamma-aminobutyric acid type A receptors (GABAA) agonist diazepam (DZP; 3mg/kg, p.o.) as a positive control. A vehicle (10mL/kg) was served as control. The tested chemicals, single-dose LIN (50mg/kg) and SES (50mg/kg), as well as a combination (LIN+SES) and (DZP+LIN+SES), were administered orally in order to conduct several behavioral tests, including open-field, swings box, hole-crossing, and dark-resident time tests. Further, molecular docking studies of LIN, SES, and DZP were carried out through different software. The results showed that LIN and SES individually have significant anxiolytic-like activity in mice. Further, when LIN was combined with SES and with (SES+DZP), it exhibited a relatively lower locomotor activity in mice compared to individual treatment groups, indicating a synergistic action. In addition, the molecular docking analysis revealed that LIN and SES have a moderate binding affinity (-5.0 and -5.1kcal/mol) toward the GABAA receptor α3 subunit. In conclusion, our findings suggest that LIN and SES exerted synergistic anxiolytic activity on Swiss albino mice, possibly through the GABAergic interaction pathways.

Perinatal Photoperiod Has Long-Term Effects on the Rest-Activity Cycle and Sleep in Male and Female Mice.

Environmental light conditions during development can have long-lasting effects on the physiology and behavior of an animal. Photoperiod, a clear example of environmental light conditions, is detected by and coded in the suprachiasmatic nucleus. It is therefore possible that differences observed in behavior in adulthood after exposure to different perinatal photoperiods are caused by lasting changes in the suprachiasmatic nucleus or alternatively, in other nuclei affected by perinatal photoperiod. It can then be expected that behavior with strong circadian aspects, like rest-activity and sleep, are affected by difference in photoperiod during development as well. To investigate this further, we exposed mice to different photoperiods during their development in the womb until weaning (long: 16 h of light, 8 h of darkness; short: 8 h of light, 16 h of darkness). After weaning, the animals were exposed to a 12 h:12 h light:dark cycle for at least 3 more weeks and some animals were subsequently exposed to constant darkness. We assessed their rest-activity patterns by recording voluntary locomotor activity and used EEG recordings to determine sleep architecture and electroencephalographic spectral density. Perinatal long photoperiod animals showed a shorter duration of locomotor activity than short photoperiod-developed mice in a 12:12 light-dark cycle. This difference disappeared in constant darkness. In the light phase, that is, during the day, perinatal long photoperiod mice spent less time awake and more time in NREM sleep than short photoperiod-developed mice. No effects of perinatal photoperiod were observed in the EEG spectral density or in response to sleep deprivation. We see lasting differences in behavioral locomotor activity and sleep in female and male mice after exposure to different perinatal photoperiods. We conclude that perinatal photoperiod programs a developing mammal for different external conditions and changes brain physiology, which in turn results in long-lasting, possibly even permanent, changes in the sleep and locomotor activity.

Locomotor and discriminative stimulus effects of NBOH hallucinogens in rodents.

Despite the efforts of the Drug Enforcement Administration to safeguard the public from hazardous analogs of synthetic hallucinogens, these compounds have increasingly been observed in the illicit drug market. Four novel compounds were found to be similar in structure to the previously described 25X-NBOMe synthetic hallucinogens. These four compounds, 25B-NBOH, 25C-NBOH, 25E-NBOH, and 25I-NBOH were evaluated for their ability to modify spontaneous locomotor activity in mice to obtain dose range and time-course information and were then tested for discriminative stimulus effects similar to the prototypical hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM). All four test compounds decreased locomotor activity. The locomotor depressant effects were similar in magnitude and potency to DOM, but less potent than the 25X-NBOMe compounds in previous reports. 25B-NBOH, 25C-NBOH, and 25E-NBOH fully substituted (≥80%) in DOM-trained rats, whereas 25I-NBOH failed to fully substitute for DOM even at doses that suppressed responding. The discriminative stimulus effects were more potent than those of DOM and the 25X-NBOMe compounds. These findings suggest that three of the four test compounds are most likely to be used as recreational hallucinogens in a similar manner to DOM and the 25X-NBOMe compounds, whereas 25I-NBOH may be less liable to illicit use.

Medial prefrontal cortex-periaqueductal gray circuit overcomes anxiety-like behavior in male mice following adversity

BackgroundInescapable stress leads to various long-lasting physical and mental dysfunctions. Acute stress exposure is linked to a high risk of psychological disorders, such as anxiety disorders. The medial prefrontal cortex (mPFC) and periaqueductal gray (PAG) are anatomical regions associated with social information processing and emotional valence. However, it is unclear whether mPFC projections to the PAG are involved in anxiety behavior. MethodsIn this study, an anxiety model by an inescapable foot shock was established. And used immunofluorescence, FosTRAP strategy, specific chemogenetics, optogenetics and behavior test to reveal that the stressful event increased the anxiety behavior of mice after exposure to foot shock and activation of mPFC-PAG circuitry can improve anxiety-like behavior and the locomotor behavior of mice. ResultsNotably, FosTRAP results indicated that c-Fos expression in the PAG and mPFC is increased during foot shock, but inhibiting these brain regions did not significantly alleviate anxiety behavior. Additionally, chemogenetic activation of mPFC projections to the PAG improved anxiety-like behavior and locomotor activity in mice only during stress. Optogenetic activation of the mPFC-PAG circuitry increased the total distance traveled in the open field test and slightly increased the number of entries into the center area, while optogenetic inhibition slightly increased anxiety-like behavior in control mice. LimitationThe limitation of this study is that only the changes and regulations of mPFC-PAG of anxiety male animals were studied. ConclusionsOverall, our findings suggest that the valence-encoding mPFC-PAG circuit modulates anxiety, and that these projections may be potential targets for treatment of anxiety disorders.

The Synergistic Effect of Curcumin and Piperine Nanoparticles on Methamphetamine-induced Neurotoxicity, Oxidative Stress, and Memory Impairments in Mice Brain

Background: Methamphetamine (METH) is a highly addictive neural stimulant that severely affects the CNS and can induce oxidative damage. Piperine and curcumin are active constituents that have numerous properties, including antioxidant, anti-inflammatory, and neuroprotective Objective: In this study, the synergistic effect of piperine and curcumin nanoparticles was investigated on the acute doses of METH-induced neurotoxicity in mice brains. Methods: METH (6 mg/kg, i.p) was administered to 14 groups of mice and piperine-curcumin nanoparticles at different doses (10, 20, 40 mg/kg and 20, 40 and 60 mg/kg, respectively) were administered. Open field test (OFT) and conditioned place preference (CPP) were used to investigate locomotor activity, anxiety-like behavior, and addictive behavior in mice. Oxidative stress biomarkers (reactive oxygen species (ROS), protein carbonyl content, lipid peroxidation, glutathione content, and mitochondrial function were evaluated in isolated brain mitochondria. Results: We found that piperine and curcumin nanoparticles significantly decreased hyperlocomotion and anxiety-like behavior in METH-treated mice. Also, METH enhanced CPP whilst piperine and curcumin nanoparticles suppressed the effect of METH-induced CPP. METH administration significantly increased ROS, protein carbonyl content, and lipid peroxidation and decreased glutathione content and mitochondrial function in the isolated brain mitochondria. Piperine and curcumin nanoparticles (at all doses) showed synergistic effects on reducing oxidative damages in a dosedependent manner compared to the METH group. Conclusion: In conclusion, combined piperine and curcumin nanoparticles showed greater neuroprotective effects against METH-induced neurotoxicity due to their greater permeability and better antioxidant properties than piperine and curcumin alone

A mouse in the spotlight: Response capacity to artificial light at night in a rodent pest species, the southern multimammate mouse (Mastomys coucha)

Multimammate mice are prolific breeders, can cause significant agricultural damage, and are reservoir hosts for a number of pathogens. They are nocturnal and given their success in urbanised rural environments, we were interested in how they would respond to increasingly bright anthropogenic spaces. We evaluated the locomotor activity of southern multimammate mice (Mastomys coucha), under four treatments: in an outdoor enclosure with natural light and temperature fluctuations, in a laboratory under a standard light regime, and two artificial light at night (ALAN) regimes (2 Lux) of varying proximity. The study animals remained nocturnal for the duration of the experiments. They were more active under the laboratory conditions with lower day-time light levels compared to the outdoor treatment but reduced their activity under ALAN. When the night light originated remotely, activity levels decreased by more than 50%, whereas under direct ALAN from above the cages, there was a 75% decrease in activity. The onset of activity was later during the two LAN treatments. We concluded that Mastomys coucha is strongly averse to light and show severe behavioural and circadian responses to light at night. We predict that it is unlikely that Mastomys will flourish in cities, but that they could thrive in and around dark urbanised refugia.

Impacts of circadian disruptions on behavioral rhythms in mice.

Circadian rhythms are fundamental biological processes that recur approximately every 24 h, with the sleep-wake cycle or circadian behavior being a well-known example. In the field of chronobiology, mice serve as valuable model animals for studying mammalian circadian rhythms due to their genetic similarity to humans and the availability of various genetic tools for manipulation. Monitoring locomotor activity in mice provides valuable insights into the impact of various conditions or disturbances on circadian behavior. In this review, we summarized the effects of disturbance of biological rhythms on circadian behavior in mice. External factors, especially light exert a significant impact on circadian behavior. Additionally, feeding timing, food composition, ambient temperature, and physical exercise contribute to variations in the behavior of the mouse. Internal factors, including gender, age, genetic background, and clock gene mutation or deletion, are effective as well. Understanding the effects of circadian disturbances on murine behavior is essential for gaining insights into the underlying mechanisms of circadian regulation and developing potential therapeutic interventions for circadian-related disorders in humans.

Characterization of novel nitazene recreational drugs: Insights into their risk potential from in vitro µ-opioid receptor assays and in vivo behavioral studies in mice

2-Benzylbenzimidazole derivatives or ‘nitazenes’ are increasingly present on the recreational drug market. Here, we report the synthesis and pharmacological characterization of 15 structurally diverse nitazenes that might be predicted to emerge or grow in popularity. This work expands the existing knowledge about 2-benzylbenzimidazole structure-activity relationships (SARs), while also helping stakeholders (e.g., forensic toxicologists, clinicians, policymakers) in their risk assessment and preparedness for the potential next generation of nitazenes. In vitro µ-opioid receptor (MOR) affinity was determined via competition radioligand (3[H]DAMGO) binding assays in rat brain tissue. MOR activation (potency and efficacy) was studied by means of a cell-based β-arrestin 2 recruitment assay. For seven nitazenes, including etonitazene, opioid-like pharmacodynamic effects (antinociception, locomotor activity, body temperature changes) were evaluated after subcutaneous administration in male C57BL/6 J mice. The results showed that all nitazenes bound to MOR with nanomolar affinities, and the functional potency of several of them was comparable to or exceeded that of fentanyl. In vivo, dose-dependent effects were observed for antinociception, locomotor activity, and body temperature changes in mice. SAR insights included the high opioid-like activity of methionitazene, iso-butonitazene, sec-butonitazene, and the etonitazene analogues 1-ethyl-pyrrolidinylmethyl N-desalkyl etonitazene and ethylene etonitazene. The most potent analogue of the panel across all functional assays was α’-methyl etonitazene. Taken together, through critical pharmacological evaluation, this work provides a framework for strengthened preparedness and risk assessments of current and future nitazenes that have the potential to cause harm to users.

The combined use of thymoquinone and metformin provides more effective neuroprotection in a mouse model of MPTP-induced Parkinson’s disease

Thymoquinone (TQ) is known for its antioxidant properties, and although metformin (MM) is known as an antidiabetic drug, it is suggested that it reduces neurodegeneration. The study aimed to investigate the neuroprotective effects of TQ and MM, particularly when used together, in relation to Parkinson’s disease (PD). In the study, sixty-eight male C57BL/6 mice weighing 25–30 g were divided into five groups as follows: control, MPTP, MPTP+TQ, MPTP+MM, and MPTP+TQ+MM. MM (500 mg/kg, orally) and TQ (5 mg/kg, i.p.) were administered for 21 days. Motor coordination and locomotor activities were evaluated by the pole test. TOS and TAS analyses were conducted to determine oxidative stress levels in the substantia nigra. Dopaminergic degeneration in the substantia nigra was evaluated by analyzing Tyrosine hydroxylase (TH). To evaluate the apoptotic pathway, the expression levels of iNOS, BDNF, Complex 1, Bax, Bcl-2, Cytochrome C, AIF, and Caspase-3 were examined immunohistochemically. Compared to the MPTP-treated group, TQ, MM and MM+TQ treatment provided significant improvement in locomotor activity in mice, significantly increased antioxidant activity, significantly reduced the expression levels of iNOS, Bax, Cytochrome C, Caspase-3, and AIF, significantly increased BDNF, Bcl-2, and Complex 1 expressions, and significantly increased the number of TH positive cells. The separate use of TQ and MM exhibits neuroprotective activity, however, we showed that using TQ and MM in combination may be more effective. This may provide preclinical evidence supporting the therapeutic potential of their combined use for treating PD.

Behavioral effects of two cannabidiol and cannabigerol-rich formulas on mice

Cannabis sativa L. produces more than 100 specific bioactive compounds, known as cannabinoids. The major non-psychotropic Cannabis constituent is cannabidiol (CBD), which displays beneficial properties in a variety of medical conditions. However, the potential therapeutic role of other minor phytocannabinoids, such as cannabigerol (CBG), and their use in combination with CBD, has remained largely unexplored. In this study, we wanted to assess the in vivo effects of two novel non-psychotropic cannabinoid formulas, both containing relatively high percentages of CBD but differing mainly for CBG content, hereafter called CBG+ and CBG-formulas. We employed different behavioral tests to evaluate the effects of these formulas at three different dosages on mice locomotor activity, anxiety-related behaviors, short-term memory and sociability. We found that these two formulas display unique behavioral profiles: CBG + formula produced an increase in mice locomotor activity and displayed anxiolytic properties, whereas both formulas improved spatial short-term memory and social interactions. The results obtained suggest that different combinations of phytocannabinoids are able to determine different behavioral effects and highlight the importance of studying the effects of less known phytocannabinoids (like CBG), which used in combination with other phytocannabinoids can change the profile of action of other active compounds (such as CBD).

Curcumin alleviates arsenic trioxide-induced neural damage in the murine striatal region.

Arsenic-induced neurotoxicity, with dose-dependent effects, is well-documented in rodents. Curcumin (CUR), a cost-effective plant polyphenol, shows neuroprotective effects by modulating oxidative stress, apoptosis, and neurochemistry. This study evaluates curcumin's neuroprotective potential against arsenic trioxide (As2O3) in the mouse striatal region. Healthy adult male mice were chronically administered with varying concentrations of As2O3 (2, 4 and 8mg/kg bw) alone and along with CUR (100mg/kg bw) orally for 45days.Towards the end of the experimental period, the animals were subjected to behavioural paradigms including open field task, novel object recognition, rota-rod, and Morris water maze. Striatal tissues were freshly collected from the animals on day 46 for biochemical analyses (MDA, GPx, and GSH). Additionally, perfusion-fixed brains were processed for morphological observations. Behavioural study showed an apparent decrease in certain cognitive functions (learning and memory) and locomotor activity in mice exposed to As2O3 compared to controls. Simultaneous treatment of As2O3 (2, 4 and 8mg/kg bw) and curcumin (100mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. As2O3 alone exposure also exhibited a significant increase in oxidative stress marker (MDA) and a decrease in antioxidant enzyme levels (GPx, GSH). Morphological alterations were noted in mice subjected to elevated doses of As2O3 (4 and 8mg/kg bw). However, these changes were reversed in mice who received As2O3 + CUR co-treatment. Collectively, our findings indicate that curcumin offers neuroprotection to the striatal region against As2O3-induced behavioral deficits, as well as biochemical and morphological alterations.

Anti-inflammatory and antinociceptive effects of Aloysia gratissima leaves essential oil: An in vivo study

Background and aimAloysia gratissima is used in popular medicine as an analgesic and sedative. However, studies on its biological activities are still scarce. Therefore, this work aimed to evaluate the antinociceptive and anti-inflammatory effect of A. gratissima leaves essential oil (OAG) in mice. Experimental procedureThe OAG was obtained by hydrodistillation and its composition was determined by gas chromatography-mass spectrometry. The sesquiterpenes pinocamphone, β-pinene, and guaiol were the major constituents of OAG. The effect of OAG (1, 10, and 30 mg/kg, p.o.) was assessed by pre-treating male mice 1h before the formalin assay, carrageenan-induced peritonitis test, or the paw edema induced by arachidonic acid (AA). The acute toxicity of OAG (2000 mg/kg, p.o.) was also investigated. Results and conclusionThe minimum effective dose of OAG in the formalin test was 1 mg/kg. This dose did not affect the locomotor activity of mice. The OAG decreased the number of leukocytes/mm³ in the peritoneal exudate of mice and reduced paw edema 45 min after the arachidonic acid injection. OAG treatment elicited a reduction in NPSH levels in the paw tissue and increased NPSH levels in mice blood plasma and did not cause mice mortality. The OAG is devoid of acute toxicity and shows anti-inflammatory activity, which can be related to the presence of pinocamphone, guaiol, and β-pinene and is mediated, at least in part, by mechanisms that involve the participation of NPSH.

Aberrant copper metabolism and hepatic inflammation cause neurological manifestations in a mouse model of Wilson’s disease

Pathogenic germline mutations in the P-type copper-transporting ATPase (ATP7B) gene cause Wilson’s disease (WD), a hereditary disorder characterized by disrupted copper metabolism. The Arg778Leu (R778L) mutation in exon 8 is prevalent among individuals with WD in East Asia and is associated with more severe phenotypes. In this study, we generated a WD mouse model harboring R778L mutation (R778L mice) using CRISPR/Cas9. R778L mice exhibit a range of pathological characteristics resembling those of patients with WD and the same point mutations, including aberrant copper metabolism, pathological cellular injury, inflammation, and severe hepatic fibrosis. At 3–5 months of age, these mice started to display neurological deficits in motor coordination and cognitive dysfunction, accompanied by increased expression of inflammatory cytokines in the central nervous system. Microglia in the striatum and cortex exhibit significant activation, shorter processes, and decreased branch points. However, the Cu2+ levels in the brain tissue of R778L mice did not differ significantly from those of wild-type mice. Notably, inhibition of hepatic inflammation with PJ34 or siNfkb markedly alleviated the deficiencies in cognitive performance and improved locomotor activity in R778L mice. Thus, this study establishes a novel murine model to investigate the pathophysiology of WD, highlights the liver-brain crosstalk responsible for neurological manifestations in individuals with WD caused by the R778L point mutation, and demonstrates the potential of modulating liver inflammation as a therapeutic strategy for alleviating the neurological manifestations of WD.

A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms.

The repeated evolution of similar phenotypes in independent lineages often occurs in response to similar environmental pressures, through similar or different molecular pathways. Recently, a repeatedly occurring mutation R263Q in a conserved domain of the protein Cryptochrome-1 (CRY1) was reported in multiple species inhabiting subterranean environments. Cryptochromes regulate circadian rhythms, and glucose and lipid metabolism. Subterranean species show changes to their circadian rhythm and metabolic pathways, making it likely that this mutation in CRY1 contributes to adaptive phenotypic changes. To identify the functional consequences of the CRY1 R263Q mutation, we generated a mouse model homozygous for this mutation. Indirect calorimetry experiments revealed delayed energy expenditure, locomotor activity and feeding patterns of mutant mice in the dark phase, but no further metabolic phenotypes - unlike a full loss of function of CRY1. Gene expression analyses showed altered expression of several canonical circadian genes in the livers of the mutant mice, fortifying the notion that CRY1 R263Q impacts metabolism. Our data provide the first characterization of a novel mutation that has repeatedly evolved in subterranean environments, supporting the idea that shared environmental constraints can drive the evolution of similar phenotypes through similar genetic changes.

Endogenous Regulator of G protein Signaling 14 (RGS14) suppresses cocaine-induced emotionally motivated behaviors in female mice.

Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational circuits. We report that RGS14 is strongly expressed in discrete regions of the ventral striatum and extended amygdala in wild-type mice, and is co-expressed with D1 and D2 dopamine receptors in neurons of the nucleus accumbens (NAc). Of note, we found that RGS14 is upregulated in the NAc in mice with chronic cocaine history following acute cocaine treatment. We found significantly increased cocaine-induced locomotor sensitization, as well as enhanced conditioned place preference and conditioned locomotor activity in RGS14-deficient mice compared to wild-type littermates. Together, these findings suggest that endogenous RGS14 suppresses cocaine-induced plasticity in emotional-motivational circuits, implicating RGS14 as a protective agent against the maladaptive neuroplastic changes that occur during addiction.

Reduced voluntary wheel running behaviour in Kiss1r knockout mice

Kisspeptin and its receptor, Kiss1r, are novel players in the central balance of energy intake and expenditure. Recent evidence also indicates that kisspeptin signalling is important in thermoregulation and generation of the circadian rhythm. We used global Kiss1r knockout mice (Kiss1r KO), which are hypogonadal and develop obesity, to determine the impact of kisspeptin on circadian related behaviour. Voluntary wheel running was examined in Kiss1r KO and wild-type (WT) mice, using gonad intact and gonadectomised (GDX) mice to account for the effects of kisspeptin on gonadal sex steroids. Intact male and female Kiss1r KO mice covered only 10% and 30% of the distance travelled each day by their respective WT controls. In all mice, most of the running activity occurred during the dark phase. GDX WT mice ran significantly less during dark periods than the intact WT. GDX Kiss1r KO male mice ran significantly less than the GDX WT male mice, but the decrease was attenuated compared to intact mice. There was no difference between the female GDX Kiss1r KO and GDX WT. In contrast to the obese phenotype that develops in Kiss1r KO mice, body mass at the end of the study was significantly lower in the GDX Kiss1r KO than it was in the GDX WT mice. The difference in wheel running activity was not associated with any histological change in WAT, BAT, or muscle diameter. No difference in immunohistochemistry expression was seen in lateral hypothalamic orexin neurons or dopamine neurons in the ventral tegmental area / substantia nigra. We observed increased Iba1 expression (activation of microglia) in the arcuate nucleus of male Kiss1r KO mice. Overall, the circadian locomotor activity in male Kiss1r KO mice appears dependant on kisspeptin signalling and the obese phenotype does not develop in Kiss1r KO mice when they engage in voluntary activity.

Scopoletin and rutin attenuate ethanol reward in mouse-conditioned place preference test

IntroductionIn Traditional Chinese Medicine (TCM), Morinda citrifolia Linn. (Hai ba ji), is utilized for its various parts such as leaves, fruits, flowers, roots, and bark, serving as a tonic and addressing ailments including fever, skin, eye, throat, and gum issues, as well as nausea, vomiting, and neurological diseases. Previous research indicated that M. citrifolia Linn. fruit and its juice reduced ethanol-conditioned place preference (CPP) in mice, with scopoletin (SCOP) and rutin (RUT) proposed as the main bioactive compounds responsible for this effect. This study aimed to evaluate the impact of SCOP and RUT on ethanol reward using the CPP test in mice. MethodsThe CPP protocol consisted of a habituation phase spanning 3 days, a 1-day preconditioning phase, 10 days of conditioning, a rest day, and a post-conditioning day. The vehicle-saline control and vehicle-ethanol control groups received oral administration of a 1 % w/v solution of sodium carboxymethyl cellulose (CMC) at a dosage of 10 ml/kg. SCOP and RUT were administered orally at doses ranging from 0.05 to 1 mg/kg body weight (bw), while acamprosate (ACAM) was administered at a dosage of 300 mg/kg bw, all one hour before postconditioning. Statistical analyses utilized both repeated measures two-way and one-way ANOVA. ResultsOral administration of SCOP (0.05, 0.1, and 0.5 mg/kg bw) and RUT (0.05 mg/kg bw) one hour before postconditioning testing on day 16 markedly reduced ethanol CPP in mice. Additionally, SCOP and RUT at all tested doses (0.05–1 mg/kg bw, p.o.) did not induce any changes in normal locomotor activity in mice. DiscussionThese results suggest that SCOP and RUT diminish ethanol reward in mice, underscoring the therapeutic potential of these phytochemicals in managing alcohol use disorder.