[Neurobehavioral effects of explosion exposure on acute and chronic traumatic brain injury in rats].

Objective: To explore the effect of nerve injury in rats by neurobehavioral experiments, in order to provide a model and idea for further clarification of the traumatic brain injury mechanism under explosion exposure. Methods: From May 2021 to August 2022, 160 SPF male rats were randomly divided into four groups, including control group, 60 kPa group (low intensity group), 90 kPa group (medium intensity group) and 120 kPa group (high intensity group). The blast induced traumatic brain injury (bTBI) model of rats was established by using the shock tube platform to simulate the shock wave parameters of the explosion overpressure of 60 kPa, 90 kPa and 120 kPa. Acute observation was carried out after 24 h and 7 d of explosive exposure, and chronic recovery observation was carried out after 28 d and 90 d. The time effect of shock wave brain injury in different situations was discussed by open field, light dark test, active avoidance test. Finally, the results of brain injury in rats were detected by pathological tissue staining. Results: After 24 h explosion exposure, compared with the control group, the rest time of rats in low and high intensity groups increased, the total movement distance decreased, and the number of visits to the camera obscura decreased, with statistical significance (P<0.05). After 7 days of exposure, compared with the control group, the rest time of rats in high intensity group increased, and the number of visits to the obscura decreased, with statistical significance (P<0.05). After 28 and 90 days of exposure, compared with the control group, there were no significant differences in rest time, total exercise distance and times of visiting the camera obscura in all intensity groups (P>0.05). After 24 h of explosive exposure, compared with the control group, the cell morphology of rats in each intensity group was normal, and no inflammatory cell infiltration was observed. Conclusion: In the acute phase (24 h) of blast exposure, rats have no desire to explore the outside world, and shock wave exposure may damage the neurological function of rats.

Effects of long-term individual housing of middle-aged female Octodon degus on spatial learning and memory in the Barnes maze task.

Introduction: Prolonged social isolation is a form of passive chronic stress that has consequences on human and animal behavior. The present study was undertaken to elucidate whether the long-term isolation would precipitate age-related changes in anxiety and spatial learning and memory in degus. Methods: We investigated the effects of long-term social isolation on anxiety levels in the light-dark test, and spatial orientation abilities in the Barnes maze. Middle-aged female Octodon degus were allocated to either group-housed (3 animals per cage) or individually-housed for 5 months. Results: Under this experimental condition, there were no significant group differences in the anxiety level tested in the light-dark test and in the motivation to escape from the Barnes maze. There were no significant differences in cortisol levels between individually- and group-housed animals. On the last acquisition training day of spatial learning, individually- housed animals had a significantly higher number of correct responses and a smaller number of reference and working memory errors than the group-housed animals. In addition, isolated animals showed a tendency for reference and working memory impairment on the retention trial, while group-housed degus showed improvement in these parameters. Discussion and conclusion: The present study indicates that prolonged social isolation during adulthood in female degus has a dual effect on spatial orientation. Specifically, it results in a significant improvement in acquisition skills but a slight impairment in memory retention. The obtained cognitive changes were not accompanied by modification in anxiety and cortisol levels.

The potential of lemon balm (Melissa officinalis L.) essential oil as an anti-anxiety agent - is the citronellal the activity carrier?

ETHNOPHARMACOLOGICAL RELEVANCE: Among the fewest drugs discovered are those belonging to the class of anxiolytics. Although some drug targets for anxiety disorders are established, it is hard to modify and selectively choose the active principle for those targets. Thus, the ethnomedical approach to treating anxiety disorders remains one of the most prevalent ways for (self)managing the symptoms. Melissa officinalis L. (lemon balm) has been extensively used as an ethnomedicinal remedy for the treatment of different psyche-related symptoms, especially dose related to restlessness. AIM OF THE STUDY: This work aimed to evaluate the anxiolytic activity, in several in vivo models, of the essential oil extracted from Melissa officinalis (MO) and its main constituent citronellal, a widespread plant utilized for managing anxiety. MATERIALS AND METHODS: In the present study several animal models were used to assess MO anxiolytic potential in mice. The effect of the MO essential oil applied in doses ranging from 12.5 to 100 mg/kg was estimated in light/dark, hole board, and marble burying tests. In parallel doses of citronellal corresponding to the ones in the MO essential oil were applied to animals to determine if this is the activity carrier. RESULTS: The results indicate that the MO essential oil exerts anxiolytic potential in all three experimental settings by significantly altering the traced parameters. The effects of citronellal are somewhat inconclusive and should not be interpreted only as anxiolytic but rather as a combination of anti-anxiety and motor-inhibiting effects. CONCLUSIONS: In conclusion, we could say that the results of the present study provide a base for future mechanistic studies that would evaluate the activity of M. officinalis essential oil on various neurotransmitter systems involved in the generation, propagation, and maintenance of anxiety.

Loss of Tyro3 causes anxiety-relevant behavioural changes in female mice.

White-matter brain abnormalities have been found across a variety of psychiatric disorders. The extent of white matter pathology is proposed to be predictive of the severity of anxiety disorders. However, it is still unknown whether disruptions of white matter integrity precede, and are sufficient to give rise to, the behavioural symptoms. Interestingly, mood disturbances feature prominently in central demyelinating diseases such as multiple sclerosis. It is unclear whether the greater frequency of neuropsychiatric symptoms is linked to underlying neuropathology. In this study, we characterised male and female Tyro3 knockout (KO) mice using a variety of behavioural paradigms. Anxiety-related behaviours were assessed with the elevated-plus maze and light-dark box. Fear memory processing was assessed using fear conditioning and extinction paradigms. Finally, we assessed immobility time in the Porsolt swim test as a measure of depression-related behavioural despair. Surprisingly, loss of Tyro3 did not lead to manifestation of major shifts in baseline behaviour. We noted significant differences in habituation to novel environments and post-conditioning freezing levels of female Tyro3 KO mice, which are consistent with the female bias in anxiety disorders and could be indicative of maladaptive stress-responses. This study has demonstrated that white matter pathology related to a loss of Tyro3 is associated with pro-anxiety behavioural responses of female mice. Future studies could probe their contribution to increased risk for neuropsychiatric disorders when combined with stressful triggering events.

Under or Absent Reporting of Light Stimuli in Testing of Anxiety-Like Behaviors in Rodents: The Need for Standardization.

Behavioral neuroscience tests such as the Light/Dark Test, the Open Field Test, the Elevated Plus Maze Test, and the Three Chamber Social Interaction Test have become both essential and widely used behavioral tests for transgenic and pre-clinical models for drug screening and testing. However, as fast as the field has evolved and the contemporaneous involvement of technology, little assessment of the literature has been done to ensure that these behavioral neuroscience tests that are crucial to pre-clinical testing have well-controlled ethological motivation by the use of lighting (i.e., Lux). In the present review paper, N = 420 manuscripts were examined from 2015 to 2019 as a sample set (i.e., n = ~20-22 publications per year) and it was found that only a meager n = 50 publications (i.e., 11.9% of the publications sampled) met the criteria for proper anxiogenic and anxiolytic Lux reported. These findings illustrate a serious concern that behavioral neuroscience papers are not being vetted properly at the journal review level and are being released into the literature and public domain making it difficult to assess the quality of the science being reported. This creates a real need for standardizing the use of Lux in all publications on behavioral neuroscience techniques within the field to ensure that contributions are meaningful, avoid unnecessary duplication, and ultimately would serve to create a more efficient process within the pre-clinical screening/testing for drugs that serve as anxiolytic compounds that would prove more useful than what prior decades of work have produced. It is suggested that improving the standardization of the use and reporting of Lux in behavioral neuroscience tests and the standardization of peer-review processes overseeing the proper documentation of these methodological approaches in manuscripts could serve to advance pre-clinical testing for effective anxiolytic drugs. This report serves to highlight this concern and proposes strategies to proactively remedy them as the field moves forward for decades to come.

Anxiolytic effect of Anthemis nobilis L. (roman chamomile) and Citrus reticulata Blanco (tangerine) essential oils using the light-dark test in zebrafish (Danio rerio).

ETHNOPHARMACOLOGICAL RELEVANCE: The anxiety disorders are the most prevalent mental health condition, and anxiety is considered the sixth cause of disability surpassing diabetes mellitus, chronic obstructive pulmonary disease, and osteoarthritis. Besides, the COVID-19 pandemic provided an increase in the number of psychiatric diseases diagnosis in all social layers around the world. About 55%-94% of patients diagnosed with anxiety disorders are treated with benzodiazepines, meanwhile benzodiazepines can promote several adverse effects. In this way, alternative therapies, such as essential oils may offer significant benefits in the treatment of patients with anxiety disorders. However, the anxiolytic effect of these essential oils must be proper evaluated appropriate as well as the suitable dosage and side effect need further research. AIM OF THE STUDY: The aim was to evaluate the anxiolytic effect of Roman chamomile (Anthemis nobilis L.) and tangerine (Citrus reticulata Blanco) essential oils using the light-dark test in adult zebrafish (Danio rerio). MATERIAL AND METHODS: Both essential oils were analyzed by GC-MS and the major compounds were identified. The anxiolytic effect was evaluated by light-dark test in adult zebrafish. RESULTS: The results showed that roman chamomile essential oil has anxiolytic effect in adult zebrafish, whereas tangerine essential oil tends to reduce anxiety The major compounds of tangerine essential oil were limonene and γ-terpinene, and the major compounds of roman chamomile were pentadecyl-3-methyl-2-butenoate, hexadecyl-3-methyl-2-butenoate, 1-piperidinol and trans-1-ethyl-3-methyl-cyclopentane. CONCLUSIONS: The present study demonstrated that this anxiolytic effect may be attributed to the synergistic effect of the compounds present in roman chamomile essential oil, particularly the major compounds. The roman chamomile essential oil at the highest concentration showed anxiolytic effect. The tangerine essential oil showed a tendency to reduce anxiety, but it was not statistically significative. In addition, roman chamomile and tangerine essential oils did not cause cause alteration in locomotion activity and exploratory ability of the fish.

A comparative analysis of Danionella cerebrum and zebrafish (Danio rerio) larval locomotor activity in a light-dark test.

The genus Danionella comprises some of the smallest known vertebrate species and is evolutionary closely related to the zebrafish, Danio rerio. With its optical translucency, rich behavioral repertoire, and a brain volume of just 0.6 mm3, Danionella cerebrum (Dc) holds great promise for whole-brain in vivo imaging analyses with single cell resolution of higher cognitive functions in an adult vertebrate. Little is currently known, however, about the basic locomotor activity of adult and larval Danionella cerebrum and how it compares to the well-established zebrafish model system. Here, we provide a comparative developmental analysis of the larval locomotor activity of Dc and AB wildtype as well as crystal zebrafish in a light-dark test. We find similarities but also differences in both species, most notably a striking startle response of Dc following a sudden dark to light switch, whereas zebrafish respond most strongly to a sudden light to dark switch. We hypothesize that the different startle responses in both species may stem from their different natural habitats and could represent an opportunity to investigate how neural circuits evolve to evoke different behaviors in response to environmental stimuli.

Standardized Method for the Assessment of Behavioral Responses of Zebrafish Larvae.

Zebrafish are easy to breed in a laboratory setting as they are extremely fertile and produce dozens of eggs per set. Because zebrafish eggs and the skin of the early-stage larvae are transparent, their embryos and the hearts and muscles of their larvae can be easily observed. Multiple rapid analyses of heart rate and behavior can be performed on these larvae simultaneously, enabling investigation of the influence of neuroactive substances on abnormal behavior, death, and associated pathogenetic mechanisms. Zebrafish larvae are becoming increasingly popular among researchers and are used in laboratories worldwide to study various vertebrate life phenomena; more experimental systems using zebrafish will undoubtedly be developed in the future. However, based on the available literature, we believe that the conceptualization of a protocol based on scientific evidence is necessary to achieve standardization. We exposed zebrafish larvae at 6-7 days post-fertilization to 50 repeated light-dark stimuli at either 15-min or 5-min intervals. We measured the traveled distance and habituation time through a video tracking apparatus. The traveled distance stabilized after the 16th repetition when the zebrafish were exposed to light-dark stimuli at 15-min intervals and after the 5th repetition when exposed at 5-min intervals. Additionally, at 15-min intervals, the peak of the traveled distance was reached within the first minute in a dark environment, whereas at 5-min intervals, it did not reach the peak even after 5 min. The traveled distance was more stable at 5-min intervals of light/dark stimuli than at 15-min intervals. Therefore, if one acclimatizes zebrafish larvae for 1 h and collects data from the 5th repetition of light/dark stimuli at intervals of 5 min in the light/dark test, a stable traveled distance result can be obtained. The establishment of this standardized method would be beneficial for investigating substances of unknown lethal concentration.

Anxiety and Alzheimer's disease: Behavioral analysis and neural basis in rodent models of Alzheimer's-related neuropathology.

Alzheimer's disease (AD) pathology is commonly associated with cognitive decline but is also composed of neuropsychiatric symptoms including psychological distress and alterations in mood, including anxiety and depression. Emotional dysfunction in AD is frequently modeled using tests of anxiety-like behavior in transgenic rodents. These tests often include the elevated plus-maze, light/dark test and open field test. In this review, we describe prototypical behavioral paradigms used to examine emotional dysfunction in transgenic models of AD, specifically anxiety-like behavior. Next, we summarize the results of studies examining anxiety-like behavior in transgenic rodents, noting that the behavioral outcomes using these paradigms have produced inconsistent results. We suggest that future research will benefit from using a battery of tests to examine emotional behavior in transgenic AD models. We conclude by discussing putative, overlapping neurobiological mechanisms underlying AD-related neuropathology, stress and anxiety-like behavior reported in AD models.

Correlation of distinct behaviors to the modified expression of cerebral Shank1,3 and BDNF in two autistic animal models.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder featuring altered neuronal circuitry and consequently impaired social interactions, restrictive interests plus repetitive stereotypic activities. In the present study, differentiated behaviors of valproic (VPA) and propionic (PPA) acid-mediated autism rats were correlated to cerebral scaffolding proteins (Shank1,3) and BDNF expression variations. Sprague-Dawley offspring that received VPA during pregnancy displayed a notably diminished permanence (-78 %, p < 0.01) in the light chamber of light dark (LD) test, reduced exploratory tasks, i.e. grooming (-90 %) and rearing (-65 %). Moreover, they executed extremely greater climbing intervals (+300 %, p < 0.001) in novel cage (NC) test, plus exhibited an extremely reduced (-331 %) discrimination index in novel object recognition (NOR) test when compared to controls. PPA-treated postnatal days (PND) 12-16 rats also displayed anxiety-like behaviors, although in a less evident manner, as indicated by a moderate time (+55 %; p < 0.05) spent in dark chamber along with notable and moderate decreases in digging (-78 %) plus grooming (-52 %), respectively. Contextually, VPA- more than PPA supplied opposite Shank1,3 expression changes in cerebellum (CB; -62 %; +78 %), dorsomedial prefrontal cortex (DM-PFC; +95 % -76 %), respectively, while resulting extremely upregulated in hippocampus (HIP; +125 % - +155 %). Even BDNF resulted to be substantially and notably diminished in HIP (-85 %) and DM-PFC (-72 %), respectively, of VPA rats while it was only moderately reduced (-35 % to -45 %) in these same areas of PPA rats. The early altered brain-specific expression levels accounting for different behavioral performances may provide useful diagnostic indications and constitute valuable therapeutic strategies for autistic patients.

Anxiolytic-Like Action of Selected 4-(Alkylamino)-3-nitrocoumarin Derivatives in BALB/c Mice.

In this work, we explored the possible polypharmacological potential of the already established antimicrobials against gastrointestinal pathogens, 4-(alkylamino)-3-nitrocoumarins, as antianxiety agents, using a battery of in vivo experiments. Three chosen coumarin derivatives, differing in the substituent (sec-butylamino, hexadecylamino, or benzylamino) at position 4, at the doses of 25, 50 and 100 mg kg-1 , were evaluated in light/dark, open-field, horizontal wire and diazepam-induced sleep models using male BALB/c mice. Depending on the applied dose, all three tested coumarins displayed a noteworthy anxiolytic-like effect. 4-(sec-Butylamino)-3-nitro-2H-chromen-2-one and 4-(hexadecylamino)-3-nitro-2H-chromen-2-one could be recognized as true anxiolytics in the lowest applied dose, based on three tests, without exerting any sedative effects. Thus, the 3-nitrocoumarin core deserves further chemical diversity exploration in the 'antianxiety' direction.

Repeated but not acute exposure with a low dose range of the nitric oxide (NO) donor sodium nitroprusside (SNP) induces anxiolytic-like behaviour in a dose-independent manner in two different rat models of anxiety.

Sodium nitroprusside (SNP) is a nitric oxide (NO) donor which actually is under assessment as a potential candidate for the treatment of schizophrenia. It is well documented that anxiety symptoms are a prominent future in various psychiatric diseases comprising schizophrenia. Prior research has shown that acute challenge with SNP (1-3 mg/kg) induced anti-anxiety effects in rats but these effects at high doses were confounded by sedation and were disappeared after repeated application of it. It is still unknown if administration of a lower SNP dose range, either acutely or sub-chronically, could induce anxiolytic-like behaviour. The present study was designed to investigate this issue in rats. For this aim, the light/dark and the open field tests were used. Acute challenge with SNP (0.1 and 0.3 mg/kg, 30 min before testing) did not affect rodents' performance in the above mentioned behavioural paradigms. Conversely, rats treated sub-chronically with SNP (0.1 and 0.3 mg/kg, once per day, for 5 consecutive days), displayed longer time spent in the light chamber of the light/dark box and in the central area of the open field with respect to their vehicle-treated counterparts. Interestingly, SNP did not influence the first latency to enter the dark chamber and the number of transitions between the light and dark compartments of the apparatus in the light/dark test and did not modify the number of squares crossed, grooming episodes and rearings in the open field test. Finally, acute administration of SNP (0.1, 0.3 and 1 mg/kg, 10 min before testing) also did not influence rats' performance in the light/dark test. The present results indicate that short-term repeated but not acute application of a range of low doses of the NO donor SNP in a dose-independent manner induced an anti-anxiety behaviour in the rat which was not accompanied by undesired effects.

Synthesis and characterization of newly synthesized neodymium zirconate zinc sulfide nanocomposite and its effect on selected aspects of albino mice behavior.

Present study was conducted to report the effect of variable doses of neodymium zirconate zinc sulfide nanocomposite on behavior of albino mice of both sexes. Five-week-old albino mice (C57BL/6 strain) of both sexes were orally treated either with 10 mg (low dose) or 20 mg/ml saline/kg body weight (high dose) of neodymium zirconate zinc sulfide nanocomposite for 11 days. An untreated control group was maintained in parallel for same duration that received saline solution orally. A series of neurological (rotarod, light and dark box, open field, and novel object recognition) tests were conducted in all treatments. Oral supplementation of both low and high dose of nanocomposite significantly reduced the rotarod test performance as well as stretch attend reflex in male mice during light dark box test. Male mice treated with high dose of neodymium zirconate zinc sulfide nanocomposite had significantly increased time mobile and decreased time immobile than control group during open field test. Female mice treated with 10 mg/ml saline/kg body weight of neodymium zirconate zinc sulfide nanocomposite had significantly more line crossing during trial 1, and they spend more time with object A during trial 2 of novel object recognition test than their saline-treated control group. Change in body weight remained unaffected when compared between nanocomposite treated and untreated albino mice. In conclusion, we are reporting that both the applied doses of neodymium zirconate zinc sulfide nanocomposite are drastically affecting the muscular activity and exploratory behavior in male albino mice, while the studied behavioral tests, in general, remained unaffected in female albino mice.

Exposure of Larval Zebrafish to the Insecticide Propoxur Induced Developmental Delays that Correlate with Behavioral Abnormalities and Altered Expression of hspb9 and hspb11.

Recent studies suggest that organophosphates and carbamates affect human fetal development, resulting in neurological and growth impairment. However, these studies are conflicting and the extent of adverse effects due to pesticide exposure warrants further investigation. In the present study, we examined the impact of the carbamate insecticide propoxur on zebrafish development. We found that propoxur exposure delays embryonic development, resulting in three distinct developmental stages: no delay, mild delay, or severe delay. Interestingly, the delayed embryos all physically recovered 5 days after exposure, but behavioral analysis revealed persistent cognitive deficits at later stages. Microarray analysis identified 59 genes significantly changed by propoxur treatment, and Ingenuity Pathway Analysis revealed that these genes are involved in cancer, organismal abnormalities, neurological disease, and hematological system development. We further examined hspb9 and hspb11 due to their potential roles in zebrafish development and found that propoxur increases expression of these small heat shock proteins in all of the exposed animals. However, we discovered that less significant increases were associated with the more severely delayed phenotype. This raises the possibility that a decreased ability to upregulate these small heat shock proteins in response to propoxur exposure may cause embryos to be more severely delayed.

Involvement of anxiety-like behaviors and brain oxidative stress in the chronic effects of alarm reaction in zebrafish populations.

Aversive conditions elicit anxiety responses that prepare the organism to an eventual threat. Nonetheless, prolonged anxiety is a pathological condition associated with various neuropsychiatric disorders. Here, we evaluated whether the conspecific alarm substance (CAS), a chemical cue that elicits aversion, influences anxiety-like behaviors and modulates brain oxidative stress-related parameters in wild-type (WT) and leopard (leo) zebrafish following a repeated exposure protocol. CAS exposure was performed for 5 min, once daily for 7 consecutive days. In the 8th day, animals were tested in the light/dark and novel tank tests and their brains were further dissected for biochemical analyses. CAS chronically induced anxiogenic-like states in WT and leo populations when their behaviors were analyzed in the light/dark and novel tank tests. CAS also increased catalase (CAT) and glutathione S-transferase (GST) activities, as well as non-protein thiol (NPSH) content in WT and leo, but only leo had increased thiobarbituric reactive substance (TBARS) levels in the brain. At baseline conditions, leo was more 'anxious' when compared to WT, displaying lower CAT activity and carbonylated protein (CP) levels. Overall, CAS chronically triggers anxiety-like behavior in zebrafish populations, which may be associated with changes in oxidative stress-related parameters. Furthermore, the use of different zebrafish populations may serve as an interesting tool in future research aiming to investigate the neurobehavioral bases of neuropsychiatric disorders in vertebrates.

Zebrafish Larvae as a Behavioral Model in Neuropharmacology.

Zebrafish larvae show a clear and distinct pattern of swimming in response to light and dark conditions, following the development of a swim bladder at 4 days post fertilization. This swimming behavior is increasingly employed in the screening of neuroactive drugs. The recent emergence of high-throughput techniques for the automatic tracking of zebrafish larvae has further allowed an objective and efficient way of finding subtle behavioral changes that could go unnoticed during manual observations. This review highlights the use of zebrafish larvae as a high-throughput behavioral model for the screening of neuroactive compounds. We describe, in brief, the behavior repertoire of zebrafish larvae. Then, we focus on the utilization of light-dark locomotion test in identifying and screening of neuroactive compounds.

The influence of exercise on anxiety-like behavior in zebrafish (Danio rerio).

In non-human mammals, exercise has been shown to decrease anxiety-like behavior. Conversely, a number of studies have reported no effect or even an increase in anxiety-like behavior after exercise, however, inconsistent training regimes and behavioral paradigms across studies may be confounding the results. Zebrafish (Danio rerio) are a well-established animal model in neurobehavioral research, and have the potential to shed new insight into the effects of exercise on anxiety-like behavior where previous research has been limited, due to the ability to precisely control intensity and duration of exercise, and the validation of tests for measuring different aspects of anxiety-like behaviors. In the current study, fish were split between two treatment groups; Exercised and Control. Fish in the exercised condition were aerobically challenged (max water velocity: 0.5 m/s) using a swim tunnel one hour a day, five days a week, for six weeks. Control fish spent an equal amount of time in the swim tunnel but were not aerobically challenged (max water velocity: 0.05 m/s). After six weeks, all fish were tested individually in two standard complimentary anxiety tests for zebrafish: the novel tank test and the light-dark test. Exercised fish exhibited reduced anxiety-like behaviors in the novel tank test; they spent more time in the top and were quicker to enter the top of a novel tank compared to Control fish. In addition, Exercised fish spent more time in the light compartment of the light-dark test compared to Control fish. Our results demonstrate the beneficial effect of exercise on anxiety-like behavior in zebrafish.

The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish.

3,4-Methylenedioxymethamphetamine (MDMA) and its derivatives, 2,5-dimethoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), are recreational drugs whose pharmacological effects have recently been attributed to serotonin 5HT2A/C receptors. However, there is growing evidence that the oxytocin (OT)/vasopressin system can modulate some the effects of MDMA. In this study, MDMA (2.5-10 mg/kg), DOB (0.5 mg/kg), or PMA (0.005, 0.1, or 0.25 mg/kg) were administered intramuscularly to adult zebra fish, alone or in combination with the V1a vasopressin antagonist, SR49059 (0.01-1 ng/kg), before carrying out conditioned place preference (CPP), social preference, novel tank diving, and light-dark tests in order to evaluate subsequent rewarding, social, and emotional-like behavior. The combination of SR49059 and each drug progressively blocked: (1) rewarding behavior as measured by CPP in terms of time spent in drug-paired compartment; (2) prosocial effects measured on the basis of the time spent in the proximity of a nacre fish picture; and (3) anxiolytic effects in terms of the time spent in the upper half of the novel tank and in the white compartment of the tank used for the light-dark test. Antagonism was obtained at SR49059 doses which, when given alone, did not change motor function. In comparison with a control group, receiving vehicle alone, there was a three to five times increase in the brain release of isotocin (the analog of OT in fish) after treatment with the most active doses of MDMA (10 mg/kg), DOB (0.5 mg/kg), and PMA (0.1 mg/kg) as evaluated by means of bioanalytical reversed-phase high-performance liquid chromatography. Taken together, these findings show that the OT/vasopressin system is involved in the rewarding, prosocial, and anxiolytic effects of MDMA, DOB, and PMA in zebra fish and underline the association between this system and the behavioral alterations associated with disorders related to substance abuse.

Correlation between photoreceptor injury-regeneration and behavior in a zebrafish model.

Direct exposure to intensive visible light can lead to solar retinopathy, including macular injury. The signs and symptoms include central scotoma, metamorphopsia, and decreased vision. However, there have been few studies examining retinal injury due to intensive light stimulation at the cellular level. Neural network arrangements and gene expression patterns in zebrafish photoreceptors are similar to those observed in humans, and photoreceptor injury in zebrafish can induce stem cell-based cellular regeneration. Therefore, the zebrafish retina is considered a useful model for studying photoreceptor injury in humans. In the current study, the central retinal photoreceptors of zebrafish were selectively ablated by stimulation with high-intensity light. Retinal injury, cell proliferation and regeneration of cones and rods were assessed at 1, 3 and 7 days post lesion with immunohistochemistry and in situ hybridization. Additionally, a light/dark box test was used to assess zebrafish behavior. The results revealed that photoreceptors were regenerated by 7 days after the light-induced injury. However, the regenerated cells showed a disrupted arrangement at the lesion site. During the injury-regeneration process, the zebrafish exhibited reduced locomotor capacity, weakened phototaxis and increased movement angular velocity. These behaviors matched the morphological changes of retinal injury and regeneration in a number of ways. This study demonstrates that the zebrafish retina has a robust capacity for regeneration. Visual impairment and stress responses following high-intensity light stimulation appear to contribute to the alteration of behaviors.

Comparative Analyses of Zebrafish Anxiety-Like Behavior Using Conflict-Based Novelty Tests.

Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized in neuroscience research and central nervous system (CNS) drug discovery. Representing the most commonly used zebrafish anxiety models, the novel tank test (NTT) focuses on zebrafish diving in response to potentially threatening stimuli, whereas the light-dark test (LDT) is based on fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate the utility of these two tests, combining meta-analyses of published literature with comparative in vivo behavioral and whole-body endocrine (cortisol) testing. Overall, the NTT and LDT behaviors demonstrate a generally good cross-test correlation in vivo, whereas meta-analyses of published literature show that both tests have similar sensitivity to zebrafish anxiety-like states. Finally, NTT evokes higher levels of cortisol, likely representing a more stressful procedure than LDT. Collectively, our study reappraises NTT and LDT for studying anxiety-like states in zebrafish, and emphasizes their developing utility for neurobehavioral research. These findings can help optimize drug screening procedures by choosing more appropriate models for testing anxiolytic or anxiogenic drugs.