Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine.

BACKGROUND: Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. AIM: The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph). METHODS: Wistar rats were given 14 days of m-amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low-frequency stimulation (LFS) or continuous high-frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field tests and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. RESULTS: M-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M-amph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. CONCLUSION: These results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.

The Revised Suicide Crisis Inventory (SCI-2): Factor Structure, Internal Consistency, and Validity in a Brazilian Sample.

OBJECTIVE: To examine the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory (SCI-2) among Brazilian adults. METHODS: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 individuals in the Brazilian community. Confirmatory factor analyses, internal consistency, and convergent and criterion validity against the suicidal narrative, stressful life events, suicidal ideation, and suicide attempts were examined. RESULTS: The revised one-factor model of the SCI-2 resulted in adequate, but not optimal, model fit (χ2[1539] = 31,442.79, p < .001, CFI = .99, TLI = .99, RMSEA = .09, SRMR = .05). The revised five-factor model, on the other hand, demonstrated good fit (χ2[1529] = 14,174.86, p < .001, CFI = 1.00, TLI = 1.00, RMSEA = .06, SRMR = .04). Comparison of these two models indicated that the five-factor exhibited a superior model fit to the one-factor model. The SCI-2 total and subscales showed strong internal consistency, good convergent, and criterion validity in relation to stressful life events, suicidal narrative (except goal disengagement subscale), suicidal ideation, and suicide attempts. CONCLUSIONS: These findings indicate that the Brazilian version of the SCI-2 is a valid tool for measuring symptoms of the Suicide Crisis Syndrome.

Abbreviated Suicidal Narrative Inventory: Factor Structure, Internal Consistency, and Validity in a Brazilian Sample.

AIM: To investigate the factor structure, reliability, and validity of the Brazilian version of the Abbreviated Suicidal Narrative Inventory (SNI-38). METHODS: We used an anonymous online questionnaire of the SNI-38 and self-report measures administered between November 2020 and October 2021 in the Brazilian community. Participants were recruited through social media advertisements. Confirmatory factor analysis was carried out to test the factor structure of the SNI-38. In addition, we examined internal consistency, and convergent validity against stressful life events, the suicide crisis syndrome, suicidal ideation, and suicide attempts. RESULTS: 2660 participants were included. The eight-factor model SNI-38 had a good model fit (χ2[637] = 7,473.98, p < .001, CFI = .99, TLI = .99, RMSEA = .07, SRMR = .06); all items were significantly and positively loaded onto their respective factors (factor loadings ≥ .45). Reliability was good to high in all subscales except goal disengagement. Additionally, all subscales - except goal disengagement - were correlated positively which the suicide crisis syndrome, stressful life events, lifetime/past-month suicidal ideation, and lifetime suicide attempts. CONCLUSIONS: These findings provide preliminary support for the validity of the Brazilian version of the SNI-38, being an appropriate and valid tool for measuring suicidal narrative among Brazilian samples.

Effects of paradoxical sleep deprivation on oxidative parameters in the serum and brain of mice submitted to the animal model of hyperglycemia.

The present study aimed to investigate the effects of paradoxical sleep deprivation (PSD) on behavioral and oxidative stress parameters in the brain and serum of mice submitted to the animal model of hyperglycemia induced by alloxan, mimicking the main symptom of diabetes mellitus (DM). Adults C57BL/6 male and female mice received an injection of alloxan, and ten days later, the animals were submitted to the PSD for 36 h. The animals' behavioral parameters were evaluated in the open-field test. Oxidative stress parameters [Diacetyldichlorofluorescein (DCF), Thiobarbituric acid reactive substances (TBARS), Superoxide dismutase (SOD), and Glutathione] were assessed in the frontal cortex, hippocampus, striatum, and serum. The PSD increased the male and female mice locomotion, but the alloxan's pre-administration prevented the PSD-induced hyperactivity. In addition, the male mice receiving alloxan and submitted to the PSD had elevated latency time in the first quadrant and the number of fecal boli, demonstrating increased anxiety-like behavior. The HPA-axis was hyperactivating in male and female mice pre-administered alloxan and/or PSD-submitted animals. The oxidative stress parameters were also increased in the serum of the animals administered alloxan and/or sleep-deprived mice. Despite alloxan or PSD leading to behavioral or biochemical alterations, the one did not potentiate the other in mice. However, more studies are necessary to identify the link between sleep and hyperglycemia.

The role of interpersonal stressors and connectedness in acute suicide risk and the suicide crisis syndrome during the COVID-19 pandemic.

BACKGROUND: The global COVID-19 pandemic rapidly and drastically impacted everyday life and relationships. Fear of contracting and spreading the virus brought governments and individuals to adopt strict social distancing measures. These changes have had a significant negative impact on mental health, including a suggested increase in suicidal behaviors. The present study examined the role of interpersonal stress and connectedness in suicidal ideation, deliberate self-harm, suicide attempts, and the suicide crisis syndrome during the COVID-19 pandemic. METHODS: An international sample of 7837 adult participants was recruited across ten participating countries to complete an anonymous online battery of self-report questionnaires. Questionnaires assessed suicide-related outcomes, stressful life events (SLE), and connectedness. Multilevel regression analyses were used to examine the associations between SLE and connectedness on suicide-related outcomes within the past month. RESULTS: Interpersonal SLEs and low connectedness were associated with an increased likelihood of suicide-related outcomes and increased severity of suicide crisis syndrome. Specifically, higher rates of SLEs and lower levels of connectedness were associated with more suicide-related outcomes. LIMITATIONS: The use of a cross-sectional design and snowball sampling method may restrict the ability to establish causal relationships and limit the representativeness of the findings. CONCLUSIONS: Our findings suggest elevated suicide-related outcomes during the COVID-19 pandemic among individuals experiencing multiple interpersonal stressful life events and low connectedness with others. The circumstances of social life during the COVID-19 pandemic highlight the urgency of implementing preventive programs aimed at mitigating potential suicide risks that may arise in the aftermath of public stress situations.

Relationship Between Severity and Length of Exposure to COVID-19 Parameters and Resulting Government Responses and the Suicide Crisis Syndrome (SCS).

OBJECTIVE: The COVID-19 pandemic has had a globally devastating psychosocial impact. A detailed understanding of the mental health implications of this worldwide crisis is critical for successful mitigation of and preparation for future pandemics. Using a large international sample, we investigated in the present study the relationship between multiple COVID-19 parameters (both disease characteristics and government responses) and the incidence of the suicide crisis syndrome (SCS), an acute negative affect state associated with near-term suicidal behavior. METHODS: Data were collected from 5528 adults across 10 different countries in an anonymous web-based survey between June 2020 and January 2021. RESULTS: Individuals scoring above the SCS cut-off lived in countries with higher peak daily cases and deaths during the first wave of the pandemic. Additionally, the longer participants had been exposed to markers of pandemic severity (eg, lockdowns), the more likely they were to screen positive for the SCS. Findings reflected both country-to-country comparisons and individual variation within the pooled sample. CONCLUSION: Both the pandemic itself and the government interventions utilized to contain the spread appear to be associated with suicide risk. Public policy should include efforts to mitigate the mental health impact of current and future global disasters.

Intentions to use mental health and suicide prevention resources among individuals with symptoms of the suicide crisis syndrome and/or suicidal ideation.

INTRODUCTION: The suicide crisis syndrome (SCS) has demonstrated efficacy in predicting suicide attempts, showing potential utility in detecting at-risk individuals who may not be willing to disclose suicidal ideation (SI). The present international study examined differences in intentions to utilize mental health and suicide prevention resources among community-based adults with varying suicide risk (i.e., presence/absence of SCS and/or SI). METHODS: A sample of 16,934 community-based adults from 13 countries completed measures about the SCS and SI. Mental health and suicide prevention resources were provided to all participants, who indicated their intentions to use these resources. RESULTS: Individuals with SCS (55.7%) were just as likely as those with SI alone (54.0%), and more likely than those with no suicide-related symptoms (45.7%), to report willingness to utilize mental health resources. Those with SI (both with and without SCS) were more likely to seek suicide prevention resources (52.6% and 50.5%, respectively) than those without SI (41.7% and 41.8%); however, when examining endorsements for personal use, those with SCS (21.6%) were more likely to use resources than individuals not at risk (15.1%). CONCLUSIONS: These findings provide insight into individuals' willingness to use resources across configurations of explicitly disclosed (SI) and indirect (SCS) suicide risk.

Suicide Crisis Inventory-2: factor structure, internal consistency, and validity in a Brazilian sample

Objective: To evaluate the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory-2 (SCI-2) among Brazilian adults. Methods: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 Brazilian participants. Confirmatory factor analysis (CFA) was used to assess factor structure, internal consistency, convergent validity, and criterion validity by using measures such as suicidal narratives, stressful life events, suicidal ideation, and suicide attempts. Results: The revised one-factor model of the SCI-2 demonstrated an adequate, although not optimal, model fit (χ2[1539] = 31,442.79, p < 0.001, comparative fit index [CFI] = 0.99, Tucker-Lewis index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.09, standardized root mean residual [SRMR] = 0.05). The revised five-factor model, on the other hand, demonstrated good fit (χ2[1529] = 14,174.86, p < 0.001, CFI = 1.00, TLI = 1.00, RMSEA = 0.06, SRMR = 0.04). Comparison of these two models indicated that the five-factor model had a better fit than the one-factor model. Both the total and subscale scores of the SCI-2 showed strong internal consistency and good convergent and criterion validity in relation to stressful life events, suicidal narratives (excluding the goal disengagement subscale), suicidal ideation, and suicide attempts. Conclusion: Our findings suggest that the Brazilian version of the SCI-2 is a valid tool for assessing symptoms of suicidal crisis syndrome.

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Bipolar disorder (BD) is a chronic mental illness characterized by changes in mood that alternate between mania and hypomania or between depression and mixed states, often associated with functional impairment. Although effective pharmacological and non-pharmacological treatments are available, several patients with BD remain symptomatic. The advance in the understanding of the neurobiology underlying BD could help in the identification of new therapeutic targets as well as biomarkers for early detection, prognosis, and response to treatment in BD. In this review, we discuss genetic, epigenetic, molecular, physiological and neuroimaging findings associated with the neurobiology of BD. Despite the advances in the pathophysiological knowledge of BD, the diagnosis and management of the disease are still essentially clinical. Given the complexity of the brain and the close relationship between environmental exposure and brain function, initiatives that incorporate genetic, epigenetic, molecular, physiological, clinical, environmental data, and brain imaging are necessary to produce information that can be translated into prevention and better outcomes for patients with BD.

Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

Aumento de estresse oxidativo no sangue de pacientes com ostomia / Increased oxidative stress in the blood of ostomy patients

ABSTRACT BACKGROUND: Ostomy is a surgical procedure that creates a stoma that aims to construct a new path for the output of feces or urine. The relationship of oxidative stress (OxS) markers in patients with ostomy is still poorly described. OBJECTIVE: The present study was aimed at investigating the changes in oxidative stress parameters in peripheral blood collected from ostomy patients when compared with a healthy control group. METHODS: It was evaluated 29 ostomy patients and 30 healthy control patients. The oxidative stress parameters evaluated were: lipid peroxidation [lipid hydroperoxide (LPO), 8-isoprostane (8-ISO) and 4-hydroxynonenal (4-HNE)], protein oxidation and nitration [carbonyl and 3-nitrotyrosine (3-NT)] and DNA oxidation [8-hydroxy-2'-deoxyguanosine (8-OHDG)] in serum from ostomy patients compared to health controls. RESULTS: The data showed an increase of LPO, 8-ISO, 4-HNE, 3-NT and 8-OHDG in serum collected from ostomy patients when compared to healthy controls. CONCLUSION: The findings support the hypothesis that ostomy triggers the oxidative stress observed in the blood collected from these patients.

RESUMO CONTEXTO: Ostomia é um procedimento cirúrgico que cria um estoma com objetivo de construir um novo caminho para a saída das fezes ou urina. A relação dos marcadores de estresse oxidativo em pacientes ostomizados ainda é pouco descrita. OBJETIVO: O presente estudo tem como objetivo investigar as alterações dos parâmetros de estresse oxidativo em sangue de pacientes ostomizados comparados a controles saudáveis. MÉTODOS: Foram avaliados 29 pacientes ostomizados e 30 controles saudáveis. Os parâmetros de estresse oxidativo avaliados foram: peroxidação lipídica [hidroperóxido de lipídio (LPO), 8-isoprostano (8-ISO) e 4-hidroxinonenal (4-HNE)], oxidação e nitração de proteínas [carbonila e 3-nitrotirosina (3-NT)] e oxidação do DNA [8-hidroxi-2'-desoxiguanosina (8-OHDG)] em soro de pacientes ostomizados comparados a controles saudáveis. RESULTADOS: Os dados mostraram um aumento de LPO, 8-ISO, 4-HNE, 3-NT e 8-OHDG em soro de pacientes ostomizados em comparação a controles saudáveis. CONCLUSÃO: Os achados sustentam a hipótese de que a ostomia desencadeia o estresse oxidativo observado no sangue coletado destes pacientes.

Histone deacetylase activity and brain-derived neurotrophic factor (BDNF) levels in a pharmacological model of mania

Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity. .

Contributions of animal models to the study of mood disorders

Mood disorders are a leading cause of morbidity and mortality, yet their underlying pathophysiology remains unclear. Animal models serve as a powerful tool for investigating the neurobiological mechanisms underlying psychiatric disorders; however, no animal model developed to date can fully mimic the “corresponding” human psychiatric disorder. In this scenario, the development of different animal models contributes to our understanding of the neurobiology of these disorders and provides the possibility of preclinical pharmacologic screening. The present review seeks to provide a comprehensive overview of traditional and recent animal models, recapitulating different features and the possible pathologic mechanisms of mood disorders emulated by these models.

Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain

Objective: To investigate the effects of cannabidiol (CBD) on mitochondrial complex and creatine kinase (CK) activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg) in an acute (single dose) or chronic (once daily for 14 consecutive days) regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex. Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV) and CK in the rat brain. Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity) by CBD could be an important mechanism implicated in the action of CBD. .

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain / Diminuição dos níveis de BDNF em amígdala e hipocampo após a administração intracerebroventricular de ouabaína

OBJECTIVE: The present study aims to investigate the effects of ouabain intracerebroventricular injection on BDNF levels in the amygdala and hippocampus of Wistar rats.METHODS: Animals received a single intracerebroventricular injection of ouabain (10-3 and 10-2 M) or artificial cerebrospinal fluid and immediately, 1h, 24h, or seven days after injection, BDNF levels were measured in the rat's amygdala and hippocampus by sandwich-ELISA (n = 8 animals per group).RESULTS: When evaluated immediately, 3h, or 24h after injection, ouabain in doses of 10-2 and 10-3 M does not alter BDNF levels in the amygdala and hippocampus. However, when evaluated seven days after injection, ouabain in 10-2 and 10-3 M, showed a significant reduction in BDNF levels in both brain regions evaluated.DISCUSSION: In conclusion, we propose that the ouabain decreased BDNF levels in the hippocampus and amygdala when assessed seven days after administration, supporting the Na/K ATPase hypothesis for bipolar illness.

OBJETIVO: O presente estudo tem como objetivo investigar os efeitos da injeção intracerebroventricular de ouabaína sobre os níveis de BDNF na amígdala e no hipocampo de ratos Wistar.MÉTODOS: Os animais receberam uma única injeção intracerebroventricular de ouabaína (10-3 and 10-2 M) ou fluido cerebroespinhal artificial e, imediatamente, 3h, 24h ou sete dias após a injeção, os níveis de BDNF foram mensurados na amígdala e hipocampo dos ratos por ELISA sandwich (n = 8 animais por grupo).RESULTADOS: Quando avaliados imediatamente após a injeção, 3h ou 24h, ouabaína nas doses 10-2 e 10-3 M não alterou os níveis de BDNF em ambas as estruturas avaliadas. Entretanto, quando avaliados sete dias após a injeção, ouabaína nas doses 10-2 e 10-3 M mostrou uma significante redução nos níveis de BDNF em amígdala e hipocampo.CONCLUSÃO: Em conclusão, propõe-se que a administração de ouabaína diminuiu os níveis de BDNF em amígdala e hipocampo quando avaliados sete dias após a injeção, suportando a hipótese da participação da Na/K ATPase no transtorno bipolar.

Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases / Comparação das fases de depressão, mania e eutimia sobre os níveis de creatina quinase em pacientes bipolares

OBJECTIVE: Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic), and healthy volunteers. METHOD: Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring < 8 on the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS); manic-scoring < 7 on the HDRS and > 7 on the YMRS; depressive-scoring > 7 on the HDRS and < 7 on the YMRS. Patients in mixed phases were excluded. Blood samples were collected from all participants. RESULTS: Creatine kinase levels were higher in the manic patients than in the controls. However, we observed no significant difference between euthymic and depressive patients in terms of the creatine kinase level. CONCLUSION: Our results suggest that the clinical differences among the depressive, manic, and euthymic phases of bipolar disorder are paralleled by contrasting levels of creatine kinase. However, further studies are needed in order to understand the state-dependent differences observed in serum creatine kinase activity.

OBJETIVO: O transtorno do humor bipolar é uma doença psiquiátrica grave, recorrente e crônica associada a significativo prejuízo funcional, morbidade e mortalidade. A creatina quinase tem sido proposta como um marcador de dano cerebral. A creatina quinase é uma enzima importante principalmente para células que necessitam de uma grande quantidade de energia, como os neurônios. O objetivo do presente estudo foi comparar os níveis de creatina quinase entre as fases depressiva, maníaca e eutímica de pacientes com transtorno do humor bipolar. MÉTODO: Para avaliação dos níveis de creatina quinase no soro, 48 pacientes bipolares foram recrutados; 18 estavam eutímicos, 17 estavam em mania e 13 em episódio depressivo. Foi feita também uma comparação com um grupo controle que incluiu 41 voluntários saudáveis. Grupo eutimia: foram incluídos os pacientes que não cumpriam os critérios do DSM-IV para episódios de humor e deveriam ter a pontuação inferior a oito nas escalas de avaliação de mania (YMRS) e depressão (HDRS); grupo mania: foram incluídos os pacientes que apresentavam YMRS > 7 e HDRS < 7; grupo depressão: foram incluídos os pacientes que apresentavam HDRS > 7 e YMRS < 7. Os pacientes em episódios mistos não foram incluídos no estudo. Amostras de sangue foram coletadas de todos os participantes. RESULTADOS: Durante a mania, os níveis de creatina quinase foram aumentados em comparação com voluntários saudáveis. Entretanto, não houve diferença significativa nos níveis de creatina quinase em pacientes eutímicos e depressivos, quando comparados com o grupo controle. CONCLUSÃO: Nossos resultados sugerem que as fases maníaca, depressiva e eutímica do transtorno do humor bipolar, além de apresentarem sintomatologia distinta, também podem ser diferenciadas pelo nível de creatina quinase presente no sangue do paciente. Entretanto, mais estudos são necessários para entender as diferenças observadas na atividade da creatina quinase durante as fases do transtorno do humor bipolar.

Evaluation of light/dark cycle in anxiety- and depressive-like behaviors after regular treatment with methylphenidate hydrochloride in rats of different ages / Avaliação do ciclo claro e escuro no comportamento relacionado à ansiedade e à depressão em ratos de diferentes idades após tratamento crônico com hidrocloridrato de metilfenidato

OBJECTIVE: Methylphenidate hydrochloride is the most widely used medication for treatment and management of attention-deficit hyperactivity disorder. However, the chronic effects of methylphenidate hydrochloride on anxiety- and depressive-like rat behaviors remain poorly investigated. In this context, the present study evaluated the effects of treatment with methylphenidate hydrochloride on anxiety- and depressive-like behaviors using young and adult rats during the light and the dark cycle. METHOD: Male Wistar rats (25 or 60 days old) received a once-daily (in either the light or dark cycle) methylphenidate hydrochloride (2mg/kg) or saline intraperitoneal injection for 28 days. We performed elevated plus maze and forced swimming test two hours after the last injection. RESULTS: The light/dark cycle was a significant factor in the anxiety-like behaviors; however, no significant interaction between all three factors (cycle, age and methylphenidate hydrochloride) was found. Nevertheless, we observed a nominally significant interaction between the light/ dark cycle and age in the forced swimming test. CONCLUSION: Our results have shown that age and the light/dark cycle are more significant modulators of anxiety- and depressive-like behaviors than methylphenidate hydrochloride treatment.

OBJETIVO: Hidrocloridrato de metilfenidato é a medicação preferida para o tratamento e manutenção do transtorno de atenção e hiperatividade. No entanto, os efeitos do tratamento crônico com hidrocloridrato de metilfenidato em diferentes idades e ciclos sobre o comportamento relacionado à ansiedade e à depressão ainda não está claro. Neste contexto, o presente estudo teve como objetivo avaliar os efeitos do tratamento com hidrocloridrato de metilfenidato sobre o comportamento relacionado à ansiedade e à depressão em diferentes idades e no ciclo claro e escuro. MÉTODO: Foram utilizados ratos Wistar machos jovens e adultos que receberam uma vez ao dia (ciclo claro e escuro) hidrocloridrato de metilfenidato (2mg/kg) ou salina com injeção intraperitoneal, durante 28 dias. Após duas horas da última injeção, os animais foram submetidos ao testes de labirinto em cruz elevada e natação forçada. RESULTADOS: A fase do ciclo claro e escuro foi um fator significativo para o comportamento relacionado à ansiedade. Além disso, não houve interação significativa entre os ciclos claro e escuro, idade e metilfenidato no comportamento relacionado à ansiedade e à depressão, mas foi observada uma interação significativa entre ciclo claro e escuro e idade no teste de natação forçada. CONCLUSÃO: Nossos resultados mostraram que a idade e o ciclo claro e escuro são moduladores significativos de ambos os comportamentos quanto do tratamento com hidrocloridrato de metilfenidato.

Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats / Efeito da administração aguda da cetamina e imipramina sobre a atividade da creatina quinase no encéfalo de ratos

OBJECTIVE: Clinical findings suggest that ketamine may be used for the treatment of major depression. The present study aimed to compare behavioral effects and brain Creatine kinase activity in specific brain regions after administration of ketamine and imipramine in rats. METHOD: Rats were acutely given ketamine or imipramine and antidepressant-like activity was assessed by the forced swimming test; Creatine kinase activity was measured in different regions of the brain. RESULTS: The results showed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) reduced immobility time when compared to saline group. We also observed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in striatum and cerebral cortex. Ketamine at the highest dose (15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in cerebellum and prefrontal cortex. On the other hand, hippocampus was not affected. CONCLUSION: Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, the modulation of energy metabolism (like increase in Creatine kinase activity) by antidepressants could be an important mechanism of action of these drugs.

OBJETIVO: Vários achados clínicos sugerem que a cetamina apresenta efeito antidepressivo. O presente estudo tem como objetivo comparar efeitos comportamentais e a atividade da creatina quinase em regiões específicas do encéfalo após a administração de cetamina e imipramina em ratos. MÉTODO: Ratos Wistar receberam uma administração aguda de cetamina ou imipramina e a atividade antidepressiva foi avaliada pelo teste de nado forçado; a atividade da creatina quinase foi medida em diferentes regiões encefálicas. RESULTADOS: Os resultados mostraram que a cetamina (10 e 15mg/kg) e a imipramina (20 e 30mg/kg) diminuíram o tempo de imobilidade quando comparados ao grupo salina. Também foi observado que a cetamina (10 e 15mg/kg) e a imipramina (20 e 30mg/kg) aumentaram a atividade da creatina quinase no estriado e córtex cerebral. A dose mais alta de cetamina (15mg/kg) e a imipramina (20 e 30mg/kg) aumentaram a atividade da creatina quinase no cerebelo e córtex pré-frontal. Por outro lado, o hipocampo não foi alterado. CONCLUSÃO: Considerando que a diminuição no metabolismo provavelmente está envolvida na fisiopatologia da depressão, a modulação do metabolismo energético (como um aumento na atividade da creatina quinase) por antidepressivos pode ser um importante mecanismo de ação destes fármacos.