Effect of intensity training block on anxiety state and performance in competitive swimmers.

Background: An increase in training intensity could create changes in psychological and physiological variables in competitive athletes. For this reason, it is very relevant to know how an intensive training block could influence psychological variables in competitive swimmers. This study examined the effect of an intensive training block (HIT) for 2 weeks on the anxiety state and swimming performance compared to standard aerobic training. Methods: Twenty-two male competition swimmers were randomly assigned to two groups: HIT group (n = 11; age = 16.5 ± 0.29 years) and control group following the standard training program (n = 11; age = 16.1 ± 0.33 years). Psychological status variables (cognitive anxiety, somatic anxiety and self-confidence) and swimming performance (100-m front crawl) were measured pre-and post-test. Results: A significant effect of time was found for all psychological variables and swimming performance (F ≥ 17.6; p < 0.001; d ≥ 0.97). Furthermore, a significant group × time interaction effect was found in cognitive (F = 14.9; p < 0.001; d = 0.62) and somatic anxiety (F = 5.37; p = 0.031; d = 0.55) were found. Only a significant group effect was found in somatic anxiety (F = 27.1; p < 0.001; d = 1.2). Post hoc comparison revealed that both groups increased their cognitive anxiety and swimming performance, and decreased their self-confidence from pre to post test. However, cognitive anxiety increase significantly more in the HIT group compared to the control group. Furthermore, only the HIT training group significantly increased somatic anxiety over time, while somatic anxiety did not change significantly over time in the control group. Conclusion: Our findings indicated that a sudden increase in training intensity increased state anxiety more than standard training, but both conditions similarly enhanced swimming performance. Although the current level of psychological state is not affecting swimming performance negatively over this period, it should be regularly monitored by psychologists as it over a longer training period perhaps could have a negative influence on swimming performance.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces depression-like phenotype.

The etiology of major depressive disorder (MDD) remains poorly understood. Our previous studies suggest a role for the aryl hydrocarbon receptor (AhR) in depression. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a toxic environmental contaminant, with a high AhR binding affinity, and an established benchmark for assessing AhR activity. Therefore, this study examined the effect of TCDD on depression-like behaviors. Female mice were fed standard chow or a high-fat diet (HFD) for 11 weeks, and their weight was recorded. Subsequently, they were tested for baseline sucrose preference and splash test grooming. Then, TCDD (0.1 µg/kg/day) or vehicle was administered orally for 28 days, and mice were examined for their sucrose preference and performances in the splash test, forced swim test (FST), and Morris water maze (MWM) task. TCDD significantly decreased sucrose preference, increased FST immobility time, and decreased groom time in chow-fed mice. HFD itself significantly reduced sucrose preference. However, TCDD significantly increased FST immobility time and decreased groom time in HFD-fed mice. A small decrease in bodyweight was observed only at the fourth week of daily TCDD administration in chow-fed mice, and no significant effects of TCDD on bodyweights were observed in HFD-fed mice. TCDD did not have a significant effect on spatial learning in the MWM. Thus, this study demonstrated that TCDD induces a depression-like state, and the effects were not due to gross lethal toxicity. This study further suggests that more studies should examine a possible role for AhR and AhR-active environmental pollutants in precipitating or worsening MDD.

New insights about the antidepressant-like effects of riparin A in a chronic murine model of depression.

Riparin A is a synthetic form of natural riparins. Acute scale studies that take into consideration the structure-activity relationship have shown preliminary evidence of antidepressant and anxiolytic effects of riparin A, similar to that already known for other riparins. However, for better pharmacological characterization of this new compound, further studies are required. The aim of this work was to evaluate the effect of chronic treatment with riparin A (10 mg/kg; intraperitoneally) on depressive-like behavior in the forced swimming test and tail suspension test, as well as the reduction of anhedonia in the sucrose preference test, and on anxiety-like behavior in the open field and elevated plus maze apparatus, triggered in rats previously subjected to unpredictable chronic mild stress by 4 weeks. In addition, a pentobarbital-induced sleep time test was also used. Riparin A reduced the duration of immobility in both the forced swimming test and tail suspension test, as well as attenuated the anhedonia in the sucrose preference test. Furthermore, riparin A appears to produce anxiolytic effects in rats exposed to an open field and elevated plus maze, while increasing the alertness/vigilance in rats submitted to pentobarbital-induced sleep time test, without altering their locomotor integrity. Our results suggest that chronic riparin A appears to be a potential pharmacological target for new studies on the control of depression- and anxiety-like behaviors in stressed rats.

Antidepressant-like effects of Cimicifuga dahurica (Turcz.) Maxim. via modulation of monoamine regulatory pathways.

Sheng-ma is recorded in the Compendium of Materia Medica and mainly originates from the rhizomes of Cimicifuga dahurica (Turcz.) Maxim. (CD), Cimicifuga heracleifolia Kom. and Cimicifuga foetida L. The alcoholic extract of Cimicifuga foetida L. (Brand name: Ximingting®) has been approved for the treatment of perimenopausal symptoms accompanying hot flash, depression and anxiety in China. However, there's no further study about the antidepressant-like effects of C. dahurica (CD). The aim of this study is to investigate the antidepressant-like effect of CD extracted by 75% ethanol and its possible mechanisms.The neuro-protective effects of CD on injured PC12 cells induced by corticosterone was measured firstly. Then, forced swim test (FST), tail suspension test (TST), reserpine-induced hypothermia, 5-hydroxytryptophan (5-HTP) induced head twitch response in mice and chronic unpredictable mild stress (CUMS) on sucrose preference tests were executed. Moreover, the potential mechanisms were explored by measuring levels of monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme A (MAO-A) activities in the brains of CUMS-exposed mice. Results showed that CD (60, 120 mg/kg) can significantly decreased the immobility period in FST and TST in mice without affecting locomotor activity. CD (30 mg/kg, 60 mg/kg, 120 mg/kg) could significantly counteracted reserpine-induced hypothermia and increased the number of head-twitches in 5-HTP induced head twitch response. It was also found that the monoamine neurotransmitter levels in the hippocampus and frontal cortex were significantly increased in 60 mg/kg and 120 mg/kg CD treated mice. In addition, CD (60 and 120 mg/kg) significantly inhibited MAO-A after 6-week CUMS exposure. CD can effectively produce an antidepressant-like effect, which involved with modulation of monoamine regulatory pathways.

Differential effects of perigestational consumption of sucrose-sweetened beverages on anxiety and depression-related behaviors in adult offspring: Sex disparity in a mouse model.

Consumption of sucrose-sweetened drinks (SSDs) during pregnancy and breastfeeding can lead to various health and metabolism issues, but the potential impact on neurodevelopment and long-term effects remains unclear. This study aims to examine how maternal consumption of SSDs during gestation and lactation influences anxiety and depression-related behavior in adult offspring. Adult female CD-1 mice were randomly assigned to a control group (CG) or a sucrose group (SG) 2 weeks before gestation. The SG had 2 h of access to an SSD (15% w/w, 0.6 kcal/ml) for 2 weeks before mating, during pregnancy, and throughout lactation, totaling 8 weeks. Adult offspring were then evaluated for depressive-related behaviors and anxiety-related behaviors. Our findings reveal that perigestational consumption of SSDs does not lead to offspring presenting behaviors related to depression, but it does increase swimming behavior. However, maternal consumption of SSDs could impact the fighting response due to a diminished motivational component. In contrast, perigestational consumption of SSDs has apparent effects on anxiety-related behavior. Furthermore, female offspring appeared to be particularly vulnerable, exhibiting a higher anxiety index compared with controls. These findings indicate that females could be more vulnerable to the effects of maternal consumption of SSDs, being more susceptible to the presence of anxiety-related behaviors.

Perfectionism, disordered eating and well-being in aesthetic sports: The mediating role of passion.

Aesthetic athletes face higher risks of disordered eating, and perfectionism is one of the determinants involved. While research suggests that perfectionism in sport may play a role in physical and psychological well-being, its influence remains to be confirmed. As such, further examination of the influence of perfectionism on health is warranted as it could lead to better interventions. This preregistered research sought to shed new light on these relationships by investigating the mediating role of passion in the perfectionism-disordered eating relationship as well as physical and psychological well-being in aesthetic sports. In Study 1, 229 American recreational and competitive athletes practicing either gymnastics (n = 150) or artistic swimming (n = 79) were recruited on MTurk to complete an online questionnaire. The same recruitment procedure was used for Study 2, with 107 American gymnasts (n = 69) and artistic swimmers (n = 38) completing the questionnaire at two timepoints, one year apart. Results from path analyses showed that socially prescribed perfectionism was associated with obsessive passion, which in turn was associated with disordered eating. Self-oriented perfectionism was associated with both obsessive and harmonious passion, the latter being more adaptative as it was associated with physical and psychological well-being. Thus, the way one engages in aesthetic sports matters, as engaging with obsessive passion may take a toll on one's health and lead to disordered eating. Conversely, fostering harmonious engagement seems to temper the negative associations between perfectionism and health outcomes and promote positive relationships with athlete's well-being, but requires further study.

Antidepressant Effect of Sodium Butyrate is Accompanied by Brain Epigenetic Modulation in Rats Subjected to Early or Late Life Stress.

BACKGROUND: Major depression has a complex and multifactorial etiology constituted by the interaction between genetic and environmental factors in its development. OBJECTIVE: The aim of this study was to evaluate the effects of sodium butyrate (SD) on epigenetic enzyme alterations in rats subjected to animal models of depression induced by maternal deprivation (MD) or chronic mild stress (CMS). METHODS: To induce MD, male Wistar rats were deprived of maternal care during the first 10 days of life. To induce CMS, rats were subjected to the CMS for 40 days. Adult rats were then treated with daily injections of SD for 7 days. Animals were subjected to the forced swimming test (FST), and then, histone deacetylase (HDAC), histone acetyltransferase (HAT), and DNA methyltransferase (DNMT) activities were evaluated in the brain. RESULTS: MD and CMS increased immobility time in FST and increased HDAC and DNMT activity in the animal brains. SD reversed increased immobility induced by both animal models and the alterations in HDAC and DNMT activities. There was a positive correlation between enzyme activities and immobility time for both models. HDAC and DNMT activities also presented a positive correlation between themselves. CONCLUSION: These results suggest that epigenetics can play an important role in major depression pathophysiology triggered by early or late life stress and its treatment.

Temporal perception in closed-skill sports: An experimental study on expert swimmers and runners.

The cognitive benefits of closed-skill sports practice have so far been scantily investigated. Here, we thus focused on the potential impact of swimming and running - two sports that highly rely on a precise control of timing - on time processing. To investigate the impact of these closed-skill sports on time perception and estimation, three groups of participants (for a total of eighty-four young adults) took part in the present study: expert swimmers, expert runners, and non-athletes. The ability to process temporal information in the milliseconds and seconds range was assessed through a time reproduction and a finger-tapping tasks, while a motor imagery paradigm was adopted to assess temporal estimation of sport performance in a wider interval range. We also employed the Vividness of Movement Imagery Questionnaire to assess the individual's ability of motor imagery. Results showed that closed-skill sports, specifically time-related disciplines, enhance motor imagery and time perception abilities. Swimmers were more accurate and consistent in perceiving time when compared to runners, probably thanks to the sensory muffled environment that leads these athletes to be more focused on the perception of their internal rhythm.

Environmental enrichment affects behavioral and pharmacological response to antidepressants in CF1 mice.

It has been described that environmental enrichment (EE) exerts beneficial effects on cognitive and emotional performances, dendritic branching, synaptic density, neurogenesis and modulation of neurotrophic systems and neurotransmitters in rodents. However, the influence of EE on pharmacological and behavioral responses in animal models of psychiatric disorders has not been fully established. In this context, the aim of this study was to evaluate the influence of exposure to EE on mice behavior in the open field test (OFT) and forced swimming tests (FST), as well as the response to antidepressant drugs (fluoxetine 30 mg/kg and bupropion 30 mg/kg, p.o.). CF1 mice were exposed to an enriched housing condition at different developmental stages: from mating to postnatal day (PND) 55 (lifelong enrichment), from mating to PND21 (perinatal enrichment) and from PND21 to PND55 (post-weaning enrichment). At PND58 the male offspring were evaluated in the OFT and FST. BDNF gene expression in the hippocampus was determined through qPCR. Mice exposed to perinatal enrichment remained longer in the peripheral zone of the OFT and performed fewer grooming than mice housed under standard condition, and these effects were independent of drug treatment. Post-weaning and lifelong enrichment increased grooming behavior. Bupropion reduced grooming in all groups except in perinatal enriched. In turn, fluoxetine decreased grooming only in post-weaning enriched group. None of the enriched housing conditions altered the immobility time in the FST, which indicates that EE had no antidepressant-like effect. However, all enriched housing conditions abolished the anti-immobility effect of bupropion. None of the EE protocols affected BDNF hippocampal expression. The main conclusion is that mice behavior in the OFT is sensitive to alterations in the housing environment and depends on the developmental stage of exposure. Bupropion and fluoxetine yielded divergent responses depending on the housing condition, which suggests that EE modulates monoaminergic neurotransmission pathways.

Ansiedad precompetitiva y habilidades psicológicas relacionadas con el rendimiento deportivo / Precompetitive anxiety and psychological skills in sports performance

Antecedentes: la vinculación entre el estrés, la ansiedad y el rendimiento deportivo constituye un relevante tema de interés en el área de la psicología deportiva, si bien existe poca evidencia acerca de cómo diferentes variables pueden afectar a los niveles de ansiedad y así alterar el rendimiento deportivo. Objetivo: comparar las relaciones existentes entre las características psicológicas relacionadas con el rendimiento deportivo y ansiedad precompetitiva en una muestra de deportistas federados y no federados que difieren en sexo, edad y deporte practicado. Método: en este estudio han participado 202 deportistas con edades comprendidas entre los 18 y 30 años (X = 22,35; DT = 3,69) que practican fútbol, baloncesto, atletismo y/o natación. Resultados: se ha encontrado que existe relación entre las habilidades psicológicas relacionadas con el rendimiento deportivo y la ansiedad precompetitiva. Asimismo, se ha hallado que solo existen diferencias estadísticamente significativas en la ansiedad somática dependiendo de si el deporte practicado es individual o grupal, así como diferencias en los niveles de ansiedad precompetitiva según el sexo, si bien no hay relación diferencial en los niveles de ansiedad respecto a la edad. Conclusiones: a través de este estudio se ha pretendido aportar más evidencia empírica al ámbito de la psicología deportiva y se valoran sus beneficios.(AU)

Introduction: The link between stress, anxiety and sports performance is a relevant topic of interest in the area of sports psychology, although there is little evidence about how different variables can affect anxiety levels and thus alter sports performance. Objective: Compare the relationships between psychological characteristics related to sports performance and pre-competitive anxiety in a sample of federated and non-federated athletes differing in sex, age and sport practiced. Method: 202 sportsmen and women aged between 18 and 30 years (X = 22.35; SD = 3.69) who play football, basketball, athletics and/or swimming participated. Results: it was found that there is a relationship between psychological skills related to sports performance and pre-competitive anxiety. Likewise, it was found that there are only statistically significant differences in somatic anxiety depending on whether the sport practised is individual or group, as well as differences in the levels of pre-competitive anxiety by gender, although there is no differential relationship in the levels of anxiety with respect to age. Conclusions: the aim of this study is to provide more empirical evidence to the field of sport psychology and to assess its benefits.(AU)

Antidepressant-like Effect of 1-(2-(4-(4-Ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one in Mice: Evidence of the Contribution of the Serotonergic System.

Major depressive disorder (MDD) is a psychiatric disorder that affects a large portion of the population, with dysregulation of the serotonergic system, which is deeply involved in both the pathophysiology of MDD and mechanism of action of many antidepressants. Current pharmacological therapies do not meet the neurobiological needs of all depressed individuals, making the development of new antidepressants necessary. In recent decades, compounds containing triazoles have become promising due to their range of biological activities, including antidepressant activity. In this study, we evaluated the antidepressant-like effect of a hybrid containing triazole and acetophenone, 1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one (ETAP) (0.5-5 mg/kg), in the forced swimming test (FST) and tail suspension test (TST) in mice, as well as the involvement of the serotonergic system in this effect. Our findings demonstrated that ETAP exhibited an antidepressant-like effect from the dose of 1 mg/kg and that this effect is modulated by 5-HT2A/2C and 5-HT4 receptors. We also demonstrated that this effect may be related to inhibition of monoamine oxidase A activity in the hippocampus. Additionally, we evaluated the in silico pharmacokinetic profile of ETAP, which predicted its penetration into the central nervous system. ETAP exhibited a low potential for toxicity at a high dose, making this molecule interesting for the development of a new therapeutic strategy for MDD.

Long-lasting and sex-dependent effects of late lactational maternal deprivation on socioemotional behaviors in adult mice.

The lactation period is an important period for individual development and a sensitive period for the behavioral phenotypes and plasticity of individual offspring. Early life experiences (e.g., maternal deprivation (MD) and neglect) have significant long-lasting and dual effects on individual stress reactivities during adulthood. Theoretically, stress inoculation can improve the adaptive capacity of the body, but overstress can lead to dysfunction when adaptive mechanisms fail.To date, the potential effects of late lactational MD on the socioemotional behaviors of mouse offspring during adulthood are still not fully understood. In the present study, mice were subjected to early deprivation by individually separating pups from their dam for 0 min, 15 min, and 3 h per day from PND 13-25. The social dominance test (SDT), social interaction test (SI), open field test (OFT), and forced swim test (FST) were carried out during adulthood. The results showed that the social dominance of male mice in the 15 min/d MD group significantly increased, especially in low-rank mice. In the 3 h/d MD group, the social dominance of female mice was decreased, especially in the lower-rank mice. The anxiolytic and antidepressant-like effects of the 15 min/d MD group were significantly increased in male mice. Our study provides direct evidence that MD during late lactation period results in long-lasting effects on social dominance as well as on anxiety and depression phenotypes in a sex-dependent manner.

Antidepressant Potential of a Functionalized 3-Selanyl Benzo[b]Furan Compound in Mice: Focus on the Serotonergic System.

The present study investigated the antidepressant-like potential of a functionalized 3-selanyl benzo[b]furan (SeBZF) in male Swiss mice. To evaluate possible antidepressant-like actions, the compounds SeBZF1-5 (50 mg/kg, intragastric, i.g., route) were acutely screened in the tail suspension tests (TSTs). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) was then selected. Dose-response and time-response curves revealed that SeBFZ3 exerts antidepressant-like effects in the TST (5-50 mg/kg) and forced swimming test (FST; 50 mg/kg). Additional tests demonstrated that pretreatment with receptor antagonists WAY100635 (5-HT1A; 0.1 mg/kg, subcutaneous route), ketanserin (5-HT2A/C; 1 mg/kg, intraperitoneal, i.p.), or ondansetron (5-HT3; 1 mg/kg, i.p.) blocked the SeBZF3 antidepressant-like effects (50 mg/kg) in the TST. In addition, the coadministration of subeffective doses of SeBZF3 (1 mg/kg, i.g.) and fluoxetine (a selective serotonin reuptake inhibitor; 5 mg/kg, i.p.) produced synergistic action. A high dose of SeBZF3 (300 mg/kg) did not produce oral acute toxicity. The present results provide evidence for the antidepressant-like action of SeBZF3 and its relative safety, as well as predict the possible interactions with the serotonergic system, aiding in the development of novel options to alleviate psychiatric disabilities.

[A new method for assessing depressive-like behaviors in female mice].

Depression is a common mental disorder and mainly characterized by persistent sadness and a lack of interest or pleasure in previously rewarding or enjoyable activities. Despair is also a common symptom of depression, and the forced swim and tail suspension tests are widely used to measure this behavior in rodents, but the results from these tests can include the effects on stress resistance in addition to depressive-like states. Reduced motivation is an important marker of psychiatric disorders, including depression, and thus we have previously developed the female encounter test, a novel and simple procedure for assessing reward-seeking behavior in adult male mice. Importantly, female mice should be considered in the development of animal models of depression and assessment of mouse behaviors since the lifetime prevalence of a major depressive disorder in women is almost twice that in men, and around one in seven women can develop postpartum depression. In this review, we summarized our recent research on the male encounter test for assessing motivation in adult female mice and introduced new topics on animal models and therapeutic drugs for postpartum depression.

The Effect of Halliwick Method on Aquatic Skills of Children with Autism Spectrum Disorder.

BACKGROUND: Swimming and the skills associated with participation in the aquatic environment tend to be an integral part of the movement literacy complex. Non-participation then affects the safety of movement in the aquatic environment and may also be the reason for the limitation of movement, psychological, and social development compared to peers. METHODS: This study is a single-subject research study. The aim of this study is to evaluate the effect of a seven-week intervention program of the Halliwick method in the development of aquatic skills, gross motor skills, and mental skills relevant for aquatic competence for children with autism spectrum disorder. Seven children with autism spectrum disorder participated in swimming classes for a two-week baseline period and a seven-week intervention program of the Halliwick method, one time per week. To measure the effect in the field of aquatic skills, we used the Alyn Water Orientation Test 1. To determine the level of gross motor skills, we used the Gross Motor Function Measure test. RESULTS: There was an improvement in aquatic skills and gross motor skills in seven participants; two of them did not improve in mental adjustment oriented to the breathing control sections in the water.

Central injection of abscisic acid attenuates mood disorders induced by subchronic stress in male mice.

Stressful life increases the risk of mental and psychological disorders and cognitive deficits. Abscisic acid (ABA) is a plant hormone that has been recently discovered in mammalians. ABA is produced in response to stressful stimuli and it can reduce anxiety-like behaviors and depression and improve cognitive function. This study was designed to evaluate the effects of microinjection of ABA on depression, anxiety, passive avoidance learning and memory deficits induced by subchronic stress. ABA (10 and 15  µ $\umu $ g/mouse, i.c.v.) was administered one week after recovery period for 4 consecutive days. A three-session forced swimming test (FST) protocol for induction of subchronic stress was administered to the mice. Exploratory, anxiety-like behavior, depression and cognitive function were assessed 24 h after the last swim stress session. The results indicated that ABA (15  µ $\umu $ g/mouse) could ameliorate anxiety and depression induced by FST. In addition, ABA had no effect on the subchronic stress-induced cognitive impairments. Taken together, the results suggest that ABA could improve anxiety and depression induced by subchronic stress.

Swimming exercise strain-dependently affects maternal care and depression-related behaviors through gestational corticosterone and brain serotonin in postpartum dams.

Pregnancy is a very complex and highly stressful time in which women become more physically and emotionally vulnerable. Therefore, mothers are more likely to face decreased self-esteem and increased postpartum depression. Despite the high prevalence of postpartum depression, more than 50 % of mothers are undiagnosed or untreated, showing an urgent need to explore an effective preventive strategy. A healthy lifestyle and regular physical activity have been suggested to be associated with an increased quality of life in pregnant and postpartum women. The purpose of this study was to determine whether swimming exercise before and during pregnancy can affect maternal care and postpartum depression-related behaviors in dams. To this end, female NMRI and C57BL/6 J mice were subjected to swimming exercise before conception and throughout pregnancy. On postpartum days 1-2, maternal behavior including nest building, active nursing, and licking/grooming were monitored. A battery of behavioral tests was also used to measure depression-related symptoms including anhedonia- and anxiety-like behavior, social behavior, and behavioral despair. To identify the underlying mechanisms, corticosterone and inflammatory cytokines during late pregnancy, and corticosterone and brain serotonin during the postpartum period were measured in dams. The findings indicated that swimming exercise increased gestational corticosterone, decreased maternal care and brain serotonin, and increased all depression-related behaviors in postpartum C57BL/6 J dams, while only increased licking/grooming and social behavior, and reduced anhedonia-like behavior in postpartum NMRI dams. Taken together, this study suggests that swimming exercise before and during pregnancy could alter maternal care and postpartum depression-like behavior in a strain-dependent manner.

Validation of the forced swim test in Drosophila, and its use to demonstrate psilocybin has long-lasting antidepressant-like effects in flies.

Psilocybin has been shown to be a powerful, long-lasting antidepressant in human clinical trials and in rodent models. Although rodents have commonly been used to model psychiatric disorders, Drosophila have neurotransmitter systems similar to mammals and many comparable brain structures involved in similar behaviors. The forced swim test (FST), which has been used extensively to evaluate compounds for antidepressant efficacy, has recently been adapted for Drosophila. The fly FST has potential to be a cost-effective, high-throughput assay for evaluating potential antidepressants. For this study we pharmacologically validated the fly FST using methamphetamine, DL-α-methyltyrosine, and the antidepressant citalopram. While methamphetamine and DL-α-methyltyrosine altered overall locomotor activity in the Drosophila Activity Monitor System (DAMS), they had no significant impact on measures of immobility in the FST. Conversely, chronic citalopram decreased measures of immobility in the FST in both sexes without increasing DAMS activity. We used the validated FST to evaluate the antidepressant-like effects of high (3.5 mM) and low (0.03 mM) doses of psilocybin. Both doses of psilocybin significantly reduced measures of immobility in male flies, but not females. 0.03 mM had an effect size comparable to chronic citalopram, and 3.5 mM had an effect size approximately twice that of chronic citalopram.

Thermoregulatory significance of immobility in the forced swim test.

The forced swim test (FST) is a widely used animal model of depression and antidepressant drug screen. Rats are forced to swim on two test days in a restricted space from which there is no escape. On the first test day the rats attempt to escape and then become largely immobile; on the second test day the onset of immobility is more rapid. Immobility is said to reflect a state of lowered mood or "behavioral despair", but the validity of the FST as a model of depression has been questioned. We show here that whatever psychological states the FST may induce, immobility is water temperature dependent and thermoregulatory. In Experiment 1, separate groups of rats were first tested in water of 15, 20, 22, 25, 30, 35, 37, or 40 °C. When retested at the same temperature, reduced activity was evident only in those groups tested above 20 °C and below 37 °C. On a third test, rats previously tested in 35 °C water failed to show reduced activity in 15 °C water, whereas rats previously tested at 15 °C water did exhibit reduced activity when tested in 35 °C water. Thus, activity was dependent on current water temperature rather than prior experience. In Experiment 2, activity and body temperature were monitored during 30 min swim tests in 27 °C water. The more the animals moved, the greater the loss of body temperature. The results are consistent with a hypothesis that immobility in the FST is an adaptive thermoregulatory response that increases survival by minimizing convective heat loss. This interpretation is also aligned with best practices for survival of humans in water that is below thermoneutral.

Histological assessment of liver and stomach damage caused by pyridazinone derivative antidepressant agents.

Depression is a serious psychological disorder that affects a significant population. We investigated the antidepressant activities of four pyridazinone derivatives that contain the hydrazide moiety using the forced swimming test (FST). The compounds tested exhibited good antidepressant activity compared to duloxetine. The most promising compound was compound 2, which reduced the duration of immobility during FST. The toxic effects of the four compounds on the histomorphology of the liver and stomach tissue also was evaluated.