Behavioral Responses Of Rats Research Articles

Effects of TNF-α on Behaviour and Inflammation in Rats with Rotator Cuff Injury through NGF.

Rotator cuff injury is a common injury that includes inflammation, partial tearing, or complete tearing of the rotator cuff tendon. In cases of rotator cuff tears (RCTs), Tumor Necrosis Factor-alpha (TNF-α) can trigger the release of nerve growth factor (NGF). TNF-α is an important inflammatory mediator that affects rotator cuff activity and increased NGF expression is observed in RCTs. Therefore, this study aimed to investigate whether inhibition of TNF-α could reduce behavioural responses and inflammation levels in rats through NGF. A rat RCT model was established, and the CatWalk gait analysis system was used for behavioural assessment. Immunohistochemistry was used to detect NGF protein levels in tendon tissue. Hematoxylin eosin (HE) staining was used to observe histopathological changes. The expressions of Interleukin-1beta (IL-1β) and Cyclooxygenase-2 (COX2) were detected by western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of apoptosis protein Bcl-2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and Cysteine-aspartic acid protease-3 (Caspase-3) were detected using WB. Oxidative stress markers, namely Reactive Oxygen Species (ROS), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) were quantified in tissues using an ELISA kit. In the RCT model, elevated NGF protein expression, noticeable atrophy in the supraspinatus muscle tissue, and substantial fat infiltration were observed. The levels of IL-1β, COX2, apoptosis, and oxidative stress were all increased. TNF-α inhibition resulted in decreased NFG expression, decreased tissue fibrosis, and improved tendon atrophy. Moreover, when TNF-α was inhibited, the expressions of IL-1β and Cox2 were reduced and both apoptosis and oxidative stress were decreased. The results showed that inhibiting TNF-α had the potential to reduce inflammation levels and behavioural responses in rats. TNF-α can affect behaviour and inflammation in rats with RCTs through NGF, and TNF-α inhibition can improve rotator cuff injury.

High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats

Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

Influence of mesenchymal stromal cells of different origins on behavioural reactions of rats with cerebral ischemia-reperfusion

A new direction in cell therapy for ischemic stroke has been the use of mesenchymal stromal cells, which have shown a positive impact on functional changes in the central nervous system due to their neuroprotective effects, reduction of ischemia-reperfusion-induced injury, inhibition of ischemia-reperfusion-induced apoptosis, and restoration of motor function. This study aimed to investigate the effect of mesenchymal stromal cells of different origins, their lysate, and citicoline on the functional state of the central nervous system in rats with experimental brain ischemia-reperfusion. The study considered the effect of mesenchymal stromal cells derived from human umbilical cord Wharton’s jelly, human and rat adipose tissue, rat embryonic fibroblasts, as well as mesenchymal stromal cell lysate and citicoline on the emotional and behavioural responses of sexually mature Wistar rats (3-4 months) weighing 160-190 g. The behavioural responses of rats were studied using the open field test on the 7th and 14th days of the experiment; the following behavioural acts were recorded: ambulation (locomotion), climbing, rearing, and grooming. The significance of differences was determined using the non-parametric Mann-Whitney U test. It was established that after ischemia-reperfusion, animals with control pathology showed a significant decrease in the duration of episodes of ambulation in peripheral and central squares, vertical locomotor activity, and exploratory activity compared to the sham-operated group. In rats that received citicoline and transplanted human umbilical cord Wharton’s jelly mesenchymal stromal cells, a significant increase in the duration of episodes of horizontal locomotor activity was observed compared to other types of stem cells and the control. Intravenous administration of rat embryonic fibroblasts increased the emotional activity of the experimental animals. The least impact on locomotor and adaptive exploratory activity in rats with ischemia-reperfusion was registered in groups of animals that received mesenchymal stromal cells from human and rat adipose tissue, as well as mesenchymal stromal cell lysate. The practical significance of the study lies in the search for the most effective class of stem cells with neuroprotective properties for the creation of an injectable drug for intravenous transplantation in the treatment of patients with acute ischemic stroke

The enteric metabolite, propionic acid, impairs social behavior and increases anxiety in a rodent ASD model: Examining sex differences and the influence of the estrous cycle

Research suggests that certain gut and dietary factors may worsen behavioral features of autism spectrum disorder (ASD). Treatment with propionic acid (PPA) has been found to create both brain and behavioral responses in rats that are characteristic of ASD in humans. A consistent male bias in human ASD prevalence has been observed, and several sex-differential genetic and hormonal factors have been suggested to contribute to this bias. The majority of PPA studies in relation to ASD focus on male subjects; research examining the effects of PPA in females is scarce. The present study includes two experiments. Experiment 1 explored sex differences in the effects of systemic administration of PPA (500 mg/kg, ip) on adult rodent social behavior and anxiety (light-dark test). Experiment 2 investigated differential effects of systemic administration of PPA (500 mg/kg) on social behavior and anxiety in relation to fluctuating estrogen and progesterone levels during the adult rodent estrous cycle. PPA treatment impaired social behavior and increased anxiety in females to the same degree in comparison to PPA-treated males. As well, females treated with PPA in their diestrus phase did not differ significantly in comparison to females administered PPA in their proestrus phase, in terms of reduced social behavior and increased anxiety.

The effect of 2-oxoindoline-3-glyoxylic acid derivatives on animals’ behavioral and autonomic reactions in the open field test

ABSTRACT Screening research on the effect of 2-oxoindoline-3-glyoxylic acid derivatives on the emotional and behavioral responses of rats in the open field test was performed. 2-oxoindoline derivatives were suspended in the injection water using the Tween-80 emulsifier (one drop with 25 mg of test substance) and intraperitoneally administered at a dose of 12 mg/kg 1 hour before the first test. Diazepam was administered in the dosage of 2 mg/kg and in the same way as the investigated compounds. Neuroethological indicators have been studied including the latent period of the first movement, ambulation (horizontal activity), number of upright postures (vertical activity), the number of times animals moved to the center, autonomic balance indicators such as the number of grooming acts and defecation acts calculated by the number of fecal balls (boluses). It was found that most 2-oxoindoline derivatives suppressed or did not affect animals’ orienting and investigatory responses in the open field test. Under these conditions, the compounds suppressed emotionality manifested as a reduced number of fecal balls and grooming acts indicating a decrease in anxiety and fear in a stressful situation caused by the novelty of the open field test. Based on the analysis, it can be argued that 2-oxoindoline derivatives can modify the psychophysiological features of intact rats, i.e. their neuropsychotropic properties.

Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats.

Mechanical allodynia (pain produced by innocuous stimuli such as touch) is the main symptom of neuropathic pain. Its underlying mechanism remains to be elucidated, but peripheral nerve injury (PNI)-induced malfunction of neuronal circuits in the central nervous system, including the spinal dorsal horn (SDH), is thought to be involved in touch-pain conversion. Here, we found that intra-SDH injection of adeno-associated viral vectors including a prodynorphin promoter (AAV-PdynP) captured a subset of neurons that were mainly located in the superficial laminae, including lamina I, and exhibited mostly inhibitory characteristics. Using transgenic rats that enable optogenetic stimulation of touch-sensing Aβ fibers, we found that the light-evoked paw withdrawal behavior and aversive responses after PNI were attenuated by selective ablation of AAV-PdynP-captured SDH neurons. Notably, the ablation had no effect on withdrawal behavior from von Frey filaments. Furthermore, Aβ fiber stimulation did not excite AAV-PdynP+ SDH neurons under normal conditions, but after PNI, this induced excitation, possibly due to enhanced Aβ fiber-evoked excitatory synaptic inputs and elevated resting membrane potentials of these neurons. Moreover, the chemogenetic silencing of AAV-PdynP+ neurons of PNI rats attenuated the Aβ fiber-evoked paw withdrawal behavior and c-FOS expression in superficial SDH neurons. Our findings suggest that PNI renders AAV-PdynP-captured neurons excitable to Aβ fiber stimulation, which selectively contributes to the conversion of Aβ fiber-mediated touch signal to nociceptive. Thus, reducing the excitability of AAV-PdynP-captured neurons may be a new option for the treatment of neuropathic allodynia.

Behavioural and morphological changes in rats with lead poisoning aggravated by medicinal hypothyroidism

Relevance. Metals are transported by run-off from human settlements and industrial plants and accumulate in the sediments of water bodies. Lead is found in high concentrations in the soil of agricultural land. Lead can be transported with water, seafood, animal products and plants to humans. Poisoning may occur in workers and in the population in contact with lead. At the same time, hypothyroidism is a widespread disease, often due to living in areas of endemic iodine deficiency in water and soil. Latent hypothyroidism can aggravate occupational effects of heavy metals in exposed workers.Intention. To study behavioural and morphological changes in rats with lead poisoning aggravated by medicinal hypothyroidism. Methodology. 32 albino outbred adult male rats were studied. Lead poisoning was induced by lead acetate at a dose of 60 mg/kg body weight in drinking water tanks for 30 days. Hypothyroidism in rats was induced from the ninth day of the experiment with daily injections of thyrozol (thyroid static substance) at a dose of 30 mg/kg for 21 days. Behavioral responses in rats were studied using open field tests, and survey records were processed using Real Timer. For morphological analysis, layered serial cuts of brain tissue were prepared and painted using the Nissl method, and slides were visualized via observation microscopy.Results and Discussion. Under lead poisoning, animals demonstrated decreased locomotor and exploration activity and increased anxiety with increasing intoxication combined with hypothyroidism. Changes in the rat brain after exposure to lead were confirmed histologically: increased neuron degeneration, neuronophagia and glyosis. New histological data were obtained in case of lead-thyrozol combination: increased neuronal death, decreased number of astroglial cells compared to animals exposed to lead only. This suggests predominant irreversible neurodegeneration due to combined effects of lead poisoning and thyroidstatic exposure.Conclusion. Under combined exposure to lead and tyrozol, the thyroidstatic substance exacerbated decline in locomotor and exploration activity as well as lead-associated neurodegenerative processes in the rat brain.

CHANGES IN BEHAVIOURAL REACTIONS OF RATS FOLLOWING MODELLED TRAUMATIC BRAIN INJURY AND THEIR CORRECTION WITH TRANSCRIPTION FACTORS MODULATORS

This study aimed at investigating the effect of modulators of transcription factors NF-κB, AP-1 and Nrf2 on the behavioural responses of rats in the "Dark-light chamber" and "Open field" tests following the simulation of traumatic brain injury (TBI). The study included 42 white Wistar male rats weighing 180-220 g, divided into 6 groups of 7 rats in each: the control group included the animals exposed to the above mentioned tests before TBI modelling and 3 – 7 days after it; as for the animals of other groups, for 7 days after TBI simulation they were given intraperitoneal injections of the following transcription factor modulators: ammonium pyrrolidine dithiocarbamate, an inhibitor of nuclear translocation NF-κB, was injected in a dose of 76 mg/kg; AP-1 SR 11302 inhibitor given in a dose of 1 mg/kg; Nrf2 inductors as dimethyl fumarate given in a dose of 15 mg/kg of a 10% dimethyl sulfoxide solution and epigallocatechin-3-gallate in a dose of 1 mg/kg as well as a water-soluble form of quercetin (corvitin), which acts as an NF-κB inhibitor and Nr inducer, in a dose of 100 mg / kg (10 mg / kg in terms of quercetin). Unlike the test animals, the rats of the control group were given intraperitoneal injections of 1 ml of isotonic sodium chloride solution. It has been found out that during the first week following TBI simulation, the locomotor activity and psycho-emotional state of the rats were disturbed: the indicators of motor and exploratory activity, orienting reaction became deteriorated, anxiety and fear increased as well as the frequency of self-grooming actions. The use of inhibitors of transcription factors NF-κB (ammonium pyrolidindithiocarbamate) and AP-1 (SR 11302), Nrf2 inducers (dimethyl fumarate and epigallocatechin-3-gallate) and the water-soluble form of quercetin (corvitin) for the 1st week after TBI simulation improves motor performance and exploratory activity, orienting reaction, and reduces emotional anxiety and fear as well.

Pharmacological evaluation of the hydro-alcoholic extract of Campomanesia phaea fruits in rats.

Campomanesia phaea (Myrtaceae), popularly known as cambuci, is one of several species of plants producing comestible fruits, largely used in human nutrition. Despite its consumption and economic potential, limited scientific research is available on the Campomanesia, especially those related to its therapeutic benefits. It is reported by traditional medicine the use of the plant in the treatment of different disorders, such as cardiovascular and nervous system disturbances. So, the aim of this study was to carry out the pharmacological evaluation of the hydro-alcoholic extract (HAE) of Campomanesia fruits in rats by screening consisting of tests: a) neuropharmacological observation, b) test on the cardiovascular system. The HAE, prepared from the extraction of fruits with water/ethanol, was concentrated and freeze-dried. Behavioral responses in rats were investigated in open field test and the cardiovascular actions were investigated by a register of indirect blood pressure and the register of spontaneous beating rate right atrium. The results revealed that HAE induced grooming, hypotension and bradycardia. So, this study identified an action on the central nervous system, represented by grooming, and a cardiovascular activity of Campomanesia. The hypotension, attributed in part to bradycardia, was not related to a cholinergic effect, discarding a possible cholinomimetic action of the plant that could justify both cardiovascular and central actions.

Isoflurane and Carbon Dioxide Elicit Similar Behavioral Responses in Rats.

Euthanasia in rodents is an ongoing topic of debate due to concerns regarding the aversive nature of gases with anesthetic properties such as carbon dioxide (CO2) and isoflurane. The aim of this study was to expand upon previously published work evaluating the aversiveness of CO2 by introducing an isoflurane treatment group in parallel. Aversion was tested using a forced exposure setup and an aversion-avoidance setup. In the first part of the study, 12 naïve female Sprague-Dawley rats were exposed during four consecutive days, once to each of four treatments: isoflurane, fox urine, oxygen, and CO2. In the second part of the study, 24 naïve female Sprague-Dawley rats and 12 rats from the first experiment were exposed to CO2, isoflurane, or both gases. In the forced exposure study, there were no significant differences between CO2 and isoflurane treatments except in line crosses. Overall, rats were more active in the isoflurane and CO2 treatments compared to the control groups, suggesting that isoflurane and CO2 are similarly aversive. In the aversion-avoidance study, rats previously exposed to isoflurane left the dark chamber significantly earlier compared to naïve rats during exposure to isoflurane. We also show that learned aversion to isoflurane is sustained for at least 15 days after initial exposure. Given this result, we suggest that CO2 is superior to isoflurane when euthanizing rodents with prior exposure to isoflurane. Overall, these results confirm previous studies which suggest that care should be taken when considering the serial use of isoflurane as an anesthetic.

The study of the emotional and behavioral response in rats after introduction of the neogalenical phytocomplex from Ledum palustre shoots

While studying new medicinal products their effect on the central nervous system should be researched, namely the hypnotic and anxiolytic action of drugs should be determined. The results of the studies are necessary for further study of the drug and further preparation of the patient information leaflet. Aim. To study emotional and behavioral responses in rats after introduction of the neogalenical phytocomplex from Ledum palustre shoots. Materials and methods. The object of the study was the neogalenical phytocomplex from Ledum palustre shoots. The emotional and behavioral response was studied in two tests: “open field” and “elevated plus maze” in rats. Results . According to the results of the study conducted the neogalenical phytocomplex from Ledum palustre shoots has no sedative, hypnotic, and anxiolytic effects. Conclusions. Neogalenical phytocomplex from Ledum palustre shoots does not affect the central nervous system; therefore, theoretically, the effect of the complex studied on the ability to drive or work with other mechanisms is not expected in patients.

Aromatic Bromination Abolishes the Psychomotor Features and Pro-social Responses of MDMA ("Ecstasy") in Rats and Preserves Affinity for the Serotonin Transporter (SERT).

The entactogen MDMA (3,4-methylenedioxy-methamphetamine, “Ecstasy”) exerts its psychotropic effects acting primarily as a substrate of the serotonin transporter (SERT) to induce a non-exocytotic release of serotonin. Nevertheless, the roles of specific positions of the aromatic ring of MDMA associated with the modulation of typical entactogenic effects, using analogs derived from the MDMA template, are still not fully understood. Among many possibilities, aromatic halogenation of the phenylalkylamine moiety may favor distribution to the brain due to increased lipophilicity, and sometimes renders psychotropic substances of high affinity for their molecular targets and high potency in humans. In the present work, a new MDMA analog brominated at C(2) of the aromatic ring (2-Br-4,5-MDMA) has been synthesized and pharmacologically characterized in vitro and in vivo. First, binding competition experiments against the SERT-blocker citalopram were carried out in human platelets and compared with MDMA. Besides, its effects on platelet aggregation were performed in platelet enriched human plasma using collagen as aggregation inductor. Second, as platelets are considered an appropriate peripheral model for estimating central serotonin availability, the functional effects of 2-Br-4,5-MDMA and MDMA on ATP release during human platelet aggregation were evaluated. The results obtained showed that 2-Br-4,5-MDMA exhibits higher affinity for SERT than MDMA and fully abolishes both platelet aggregation and ATP release, resembling the pharmacological profile of citalopram. Subsequent in vivo evaluation in rats at three dose levels showed that 2-Br-4,5-MDMA lacks all key MDMA-like behavioral responses in rats, including hyperlocomotion, enhanced active avoidance conditioning responses and increased social interaction. Taken together, the results obtained are consistent with the notion that 2-Br-4,5-MDMA should not be expected to be an MDMA-like substrate of SERT, indicating that aromatic bromination at C(2) modulates the pharmacodynamic properties of the substrate MDMA, yielding a citalopram-like compound.

Influence of enalapril on the functional state of the central nervous system in experimental Alzheimer’s disease

The purpose of the work. Is To investigate the effects of enalapril on the functional state of the central nervous system of rats with experimental Alzheimer's disease.Material and methods. Experiments were carried out on non-linear laboratory white male rats weighing 0.18–0.20 kg. A model of Alzheimer's disease was created by intraperitoneal administration for 27 days of scopolamine hydrochloride (Sigma, USA) at a dose of 1 mg/kg. Starting from the 28th day of the experiment, enalapril was administered intraperitoneally at a dose of 1 mg/kg in 1 ml of saline solution — once a day, 14 days. The functional state of the central nervous system was assessed by the behavioral responses of rats in "open field" tests and "conditioned reflex of passive avoidance".Results. Behavioral reactions of rats with Alzheimer's disease after enalapril administration in the "open field" test were characterized by a decrease in the time of "immobility", an increase in the number of urinates and fecal boluses; in the test of the "conditioned reflex of passive avoidance" — an increase in the latent period of the entrance of rats into a darkened compartment connected to the electric current.Conclusions. The established behavior changes in Alzheimer's disease testify to the restoration of emotional reactions, the formation of a conditioned reflex in electrical pain stimulation, and indicate the corrective capacity of enalapril under conditions of neurodegenerative disturbances of the central nervous system.

Involvement of brain GABAAR-coupled Cl−/HCO3−-ATPase in phenol-induced the head-twitching and tremor responses in rats

Phenol-induced neurotoxicity manifests as twitching/tremor and convulsions, but its molecular mechanisms underlying the behavioral responses remain unclear. We assessed the role of the brain Cl−/HCO3−-ATPase in behavioral responses in rats following an in vivo intraperitoneal injection of phenol (20–160 mg/kg). Low concentrations of phenol (20–80 mg/kg) increased the ATPase activity as well as the head twitching responses in rat, whereas higher phenol concentrations (>60 mg/kg) increased the tremor but reduced the ATPase activity. At phenol concentrations >120 mg/kg, no ATPase activity was detected. Phenobarbital (10 mg/kg) and picrotoxin (1 mg/kg) as well as o-vanadate (2 mg/kg), significantly prevented (˜55–70%) the phenol-induced change in the behavioral responses and completely restored the enzyme activity. In vitro experiments confirmed that phenol stimulated the Cl−/HCO3−-ATPase activity at low concentrations, but had no stimulating effect on other transport ATPases. Low doses of phenol increased the formation of phosphoprotein and the rate of ATP-consuming Cl− transport by the reconstituted enzyme. The present findings provide evidence that phenol-induced neurotoxicity involves the Cl−/HCO3−-ATPase in the behavioral responses in mammals and indicate the potential benefit of this enzyme as a target for the treatment of head twitching and other types of tremor diseases.

Antistress and antidepressant activity of a plant drug in a mild chronic stress model

The effect of a complex herbal remedy on the function of the central nervous system in rats on a model of chronic unpredictable mild stress was studied in the present work. The level of stress disorders was determined by the behavioral responses in rats using the methods of “open field”, “elevated plus maze”, “forced swimming test” and “tail suspension model”, weights of target organs. It is established that the complex herbal remedy has adaptogenic, anti-stress and antidepressant effects. (For citation: Muruev BA, Gulyaev SM, Shantanova LN, Mondodoev AG. Antistress and antidepressant activity of a plant drug in a mild chronic stress model. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):69-73. doi: 10.17816/RCF16269-73).

Time-dependent effect of oligomeric amyloid-β (1–42)-induced hippocampal neurodegeneration in rat model of Alzheimer’s disease

ABSTRACTObjective: Alzheimer's disease (AD) is characterized with an abnormal deposition of insoluble amyloid-beta (Aβ) peptide plaques, tangles formation and synaptic dysfunction. These result in impaired functioning of neuronal circuits and alter the behavioral response owing to activation of neurotransmitter receptors. Recently, it has been implicated that Aβ influences N-methyl d-aspartate (NMDA) receptor activation in AD; however, the molecular mechanism underlying remains unclear. Thus, emerged specific aim to study the time-course effect of oligomeric Aβ(1–42) (oAβ1–42) on the mRNA expression of genes encoding NMDA and acetylcholine receptors in the rat model of AD.Methods: Aggregated forms of synthetic Aβ peptides were injected bilaterally into the intrahippocampal region of rat brain using stereotaxic surgery. Behavioral analysis was performed using eight-arm Radial Arm Maze task at the end of experimental period. Euthanized rat brain hippocampal tissue was used to study the mRNA expression of glutamatergic and cholinergic receptor using semiquantitative reverse transcription–polymerase chain reaction.Results: oAβ1–42 decreased the gene expression level of α7-nicotinic acetylcholine receptor and increased the mRNA expression of NMDA receptor 2A, and -2B subunits. In particular, oAβ1–42 aggregates increased the retention time and altered the behavioral response in rats after 15 days of injection. Further, amyloid-β1–42 are highly expressed in 15 days after postinjection in hippocampus of adult rats.Conclusion: Acute exposure of oAβ1–42 modulated differential gene expression of glutamatergic and cholinergic receptors in hippocampus of adult rats and is duration dependent reflecting changes in hippocampal circuitry system underlying learning and memory impairments.Abbreviations: AD: Alzheimer’s disease, Aβ: amyloid-β; oAβ1–42: oligomeric amyloid-β 1–42 full length peptide; CAM: calmodulin; CNS: central nervous system; CR: Congo red; DG: dentate gyrus; EC: entorhinal cortex; HFIP: 1,1,1,3,3,3-hexafluoro-2-propanol; IBO: ibotenic acid; NMDA: N-methyl d-aspartate; NMDAR: N-methyl d-aspartate receptor; NR2A: N-methyl d-aspartate receptor 2A; NR2B: N-methyl d-aspartate receptor 2B; ACh: acetylcholine; α7-nAChR: α7-nicotinic acetylcholine receptor; PBS: phosphate buffered saline; RAM: Radial Arm Maze; ThT: thioflavin T.

Вплив гіпоксії та мелатоніну на поведінкову реакцію щурів з різним рівнем енергетичного метаболізму

Вплив гіпоксії та мелатоніну на поведінкову реакцію щурів з різним рівнем енергетичного метаболізму

Heteromers of μ opioid and dopamine D1 receptors modulate opioid-induced locomotor sensitization in a dopamine-independent manner.

Exposure to opiates induces locomotor sensitization in rodents, which has been proposed to correspond to the compulsive drug-seeking behaviour. Numerous studies have demonstrated that locomotor sensitization can occur in a dopamine transmission-independent manner; however, the underlying mechanisms are unclear. Co-immunoprecipitation, BRET and cross-antagonism assays were used to demonstrate the existence of receptor heterodimers. Function of heterodimers was evaluated by behavioural studies of locomotor sensitization. The dopamine D1 receptor antagonist SCH23390 antagonized the signalling initiated by stimulation of μ opioid receptors with agonists in transfected cells expressing two receptors and in striatal tissues from wild-type but not D1 receptor knockout (KO) mice, suggesting that SCH23390 modified μ receptor function via receptor heteromers, as the ability of an antagonist of one of the receptors to inhibit signals originated by stimulation of the partner receptor was a characteristic of receptor heteromers. The existence of μ receptor-D1 receptor heterodimers was further supported by biochemical and biophysical assays. In vivo, when dopamine release was absent (by destruction of the dopaminergic projection from the ventral tegmental area to the striatum), SCH23390 still significantly inhibited μ receptor agonist-induced behavioural responses in rats. Additionally, we demonstrated that D1 or μ receptor KO mice and thus unable to form μ receptor-D1 receptor heterodimers, failed to show locomotor sensitization to morphine. Our results suggest that μ receptor-D1 receptor heterodimers may be involved in the dopamine-independent expression of locomotor sensitization to opiates.

Assessment of Neurotoxicity of Cultivated Plants Grown in the Neighborhood of Industrial Regions of Central Kazakhstan

The article presents the results of the impact of cultivated plants grown in summer cottage areas of three industrial regions of Central Kazakhstan on the behavioral responses of rats. It was found that prolonged feeding (three months) with vegetables, grown in areas contaminated with heavy metals, caused inhibition of locomotor activity, exploratory activity, duration of freezing behavior and lack of visits to the center that is regarded as the increase of anxiety level of rats. The results showed inhibition of behavioral responses,that testifies of the neurotoxic effect of vegetables grown in the neighbourhood of industrial regions.

Effects of bark flour of Passiflora edulis on food intake, body weight and behavioral response of rats

Effects of treatment with the bark flour of Passiflora edulis Sims, Passifloraceae, were evaluated. Adult male Wistar rats were treated for 30 days (130mg/kg, p.o.) with the albedo flour, flavedo and full bark of P. edulis, corresponding to albedo associated with flavedo. Behavioral response observed after treatment with bark flour P. edulis showed sedative effects by the reduction of exploratory activity and increased duration of immobility in the open field test for the group of animals that received the albedo flour associated with the flavedo. Sedative effects were observed in the absence of motor incoordination or muscle relaxation. Food intake of experimental animals was not changed, but the weight gain was decreased both in animals that received only albedo flour, and in those who received the full bark flour. The full bark flour of Passiflora showed sedative effects, without anxiolytic effect detectable and muscle relaxation or motor incoordination, and reduces body weight gain.