Sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.

The present study aimed to evaluate if sepsis sensitizes behavioural and biochemical responses induced by m-amphetamine. For this, Wistar rats were submitted to the cecal ligation and puncture. After 30 days of cecal ligation and puncture procedure, the animals were submitted to a single intraperitoneal injection of saline or m-amphetamine (.25, .50, or 1.0 mg/kg). Locomotor behaviour was assessed 2 h after the administration. Interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor-α, dopamine-cAMP-regulated phosphoprotein of 32,000 kDa (DARPP-32) and neuronal calcium sensor (NCS-1) levels were evaluated in the frontal cortex, hippocampus and striatum. Also, brain-derived neurotrophic factor (BDNF), neuronal growth factor and glial-derived neurotrophic factor levels were assessed in the hippocampus. M-amphetamine alone (.25 and 1.0 mg/kg) increased rats' locomotion and exploratory behaviour compared with the Sham + Sal. Animals from the cecal ligation and puncture + m-amphetamine (.5 and/or 1.0 mg/kg) group showed an increase in locomotion, exploratory and risk-like behaviour when compared with the Sham + Saline group and with its respective Sham groups. Cecal ligation and puncture increased interleukin levels compared with the Sham + Sal. However, cecal ligation and puncture animals that received m-amphetamine (1 mg/kg) increased even more, these inflammatory parameters compared with the Sham + Sal and the cecal ligation and puncture + saline group. M-amphetamine at lower doses increased neurotrophic factors, but higher doses decreased these parameters in the brain of cecal ligation and puncture rats. M-amphetamine dose-dependently increased DARPP-32 and NCS-1 levels in cecal ligation and puncture rats in some structures. In conclusion, these results demonstrate that sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.

Eating Disorder Risks Associated with Time Spent Using Social Media at an AMREC Population in the Coal Mining Region of Santa Catarina.

Comparing one's appearance to other people's and believing in an ideal body shape can negatively impact an individual. The probability of developing ED in individuals with high body dissatisfaction is higher than in the general population, leading to long-term emotional and metabolic damage. Populational studies on the prevalence of ED in Brazil are scarce in the literature. The research was carried out through the Google Forms website and evaluated risk of eating disorders through the Eating Attitude Test, degree of body dissatisfaction in the sample through the Body Shape Questionnaire and the Internet Addiction Test was used to evaluate time spent on the internet. The results showed that 84.5% of the sample were female and 62.3% of the individuals had eutrophic by the Body Mass Index. About 40.2% of the population studied had abnormal attitudes towards food, indicating a possible risk of developing ED, and 62.5% of the sample did not show body dissatisfaction. Regarding internet use, 10.8% had problematic internet use. The presence of risky eating attitudes was more prevalent in participants dissatisfied with their bodies. In addition, participants with problematic internet use had a higher risk for EDs.

Gut microbiota-brain axis in depression: The role of neuroinflammation.

Major depressive disorder (MDD) is a psychiatric condition that affects a large number of people in the world, and the treatment existents do not work for all individuals affected. Thus, it is believed that other systems or pathways which regulate brain networks involved in mood regulation and cognition are associated with MDD pathogenesis. Studies in humans and animal models have been shown that in MDD there are increased levels of inflammatory mediators, including cytokines and chemokines in both periphery and central nervous system (CNS). In addition, microglial activation appears to be a key event that triggers changes in signaling cascades and gene expression that would be determinant for the onset of depressive symptoms. Recent researches also point out that changes in the gut microbiota would lead to a systemic inflammation that in different ways would reach the CNS modulating inflammatory pathways and especially the microglia, which could influence responses to treatments. Moreover, pre- and probiotics have shown antidepressant responses and anti-inflammatory effects. This review will focus on studies that show the relationship of inflammation with the gut microbiota-brain axis and its relation with MDD.

Schizophrenia-like behavior is not altered by melatonin supplementation in rodents.

An emerging area in schizophrenia research focuses on the impact of immunomodulatory drugs such as melatonin, which have played important roles in many biological systems and functions, and appears to be promising. The objective was to evaluate the effect of melatonin on behavioral parameters in an animal model of schizophrenia. For this, Wistar rats were divided and used in two different protocols. In the prevention protocol, the animals received 1 or 10mg/kg of melatonin or water for 14 days, and between the 8th and 14th day they received ketamine or saline. In the reversal protocol, the opposite occurred. On the 14th day, the animals underwent behavioral tests: locomotor activity and prepulse inhibition task. In both protocols, the results revealed that ketamine had effects on locomotor activity and prepulse inhibition, confirming the validity of ketamine construction as a good animal model of schizophrenia. However, at least at the doses used, melatonin was not able to reverse/prevent ketamine damage. More studies are necessary to evaluate the role of melatonin as an adjuvant treatment in psychiatric disorders.

Olfactory deficit as a result of clozapine withdrawal syndrome in an animal model of schizophrenia: preliminary results.

Clozapine is an antipsychotic that produces serious withdrawal effects in schizophrenic patients. Olfactory deficits are well known as part of negative symptoms, but it is not known whether antipsychotic use and/or withdrawal are implicated. Then, we tested clozapine withdrawal in association with two widely used schizophrenia models: Neonatal immune challenge by Polycitidilic-polyinosinic acid (polyI:C) and ketamine. PolyI:C (or saline) was injected subcutaneously in neonatal period, dose of 5 mg/kg from 2 to 6 Post Natal Days, and ketamine or saline at the dose 25mg/kg intraperitoneally (i.p.), daily for 7 days from 53 to 60 post natal day. Clozapine 10mg/kg (or saline) was administered i.p. from 46 to 60 post natal day. Olfactory discrimination test (sensorial and cognitive deficit) was performed at 61 post natal day, 24h after the last injections. The association of PolyI:C, ketamine and clozapine disrupted Olfactory Discrimination, equating time in familiar and non-familiar compartments. PolyI:C plus ketamine increased crossings between compartments. It was produced, for the first time, an olfactory deficit induced by clozapine withdrawal in Wistar rats subjected to schizophrenia animal models.

The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine.

Studies have shown that schizophrenic patients seem to have nutritional deficiencies. Ascorbic acid (AA) has an important antioxidant effect and neuromodulatory properties. The aim of this study was to evaluate the effects of AA on locomotor activity and the acetylcholinesterase activity (AChE) in an animal model of schizophrenia (SZ). Rats were supplemented with AA (0.1, 1, or 10 mg/kg), or water for 14 days (gavage). Between the 9th and 15th days, the animals received Ketamine (Ket) (25 mg/kg) or saline (i.p). After the last administration (30 min) rats were subjected to the behavioral test. Brain structures were dissected for biochemical analysis. There was a significant increase in the locomotor activity in Ket treated. AA prevented the hyperlocomotion induced by ket. Ket also showed an increase of AChE activity within the prefrontal cortex and striatum prevented by AA. Our data indicates an effect for AA in preventing alterations induced by Ket in an animal model of SZ, suggesting that it may be an adjuvant approach for the development of new therapeutic strategies within this psychiatric disorder.

Antioxidant treatment ameliorates experimental diabetes-induced depressive-like behaviour and reduces oxidative stress in brain and pancreas.

Studies have shown a relationship between diabetes mellitus (DM) and the development of major depressive disorder. Alterations in oxidative stress are associated with the pathophysiology of both diabetes mellitus and major depressive disorder. This study aimed to evaluate the effects of antioxidants N-acetylcysteine and deferoxamine on behaviour and oxidative stress parameters in diabetic rats. To this aim, after induction of diabetes by a single dose of alloxan, Wistar rats were treated with N-acetylcysteine or deferoxamine for 14 days, and then depressive-like behaviour was evaluated. Oxidative stress parameters were assessed in the prefrontal cortex, hippocampus, amygdala, nucleus accumbens and pancreas. Diabetic rats displayed depressive-like behaviour, and treatment with N-acetylcysteine reversed this alteration. Carbonyl protein levels were increased in the prefrontal cortex, hippocampus and pancreas of diabetic rats, and both N-acetylcysteine and deferoxamine reversed these alterations. Lipid damage was increased in the prefrontal cortex, hippocampus, amygdala and pancreas; however, treatment with N-acetylcysteine or deferoxamine reversed lipid damage only in the hippocampus and pancreas. Superoxide dismutase activity was decreased in the amygdala, nucleus accumbens and pancreas of diabetic rats. In diabetic rats, there was a decrease in catalase enzyme activity in the prefrontal cortex, amygdala, nucleus accumbens and pancreas, but an increase in the hippocampus. Treatment with antioxidants did not have an effect on the activity of antioxidant enzymes. In conclusion, animal model of diabetes produced depressive-like behaviour and oxidative stress in the brain and periphery. Treatment with antioxidants could be a viable alternative to treat behavioural and biochemical alterations induced by diabetes.

Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats.

Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p.) or vehicle (2% Tween 80). Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

Effects of omega-3 supplementation on interleukin and neurotrophin levels in an animal model of schizophrenia.

New studies suggest that polyunsaturated fatty acids, such as omega-3, may reduce the symptoms of schizophrenia. The present study evaluated the preventive effect of omega-3 on interleukines (IL) and neurotrophin brain-derived neurotrophic factor (BDNF) levels in the brains of young rats subjected to a model of schizophrenia. Treatment was performed over 21 days, starting on the 30th day of rat's life. After 14 days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25 mg/kg) was started and maintained until the last day of the experiment. BDNF levels in the rat's prefrontal cortex were decreased at 1 h and 24 h after the last administration of ketamine, whereas the group administered with ketamine and omega-3 showed a decrease in BDNF levels only after 24 h. In contrast, both interventions induced similar responses in levels of IL-1ß and IL6. These findings suggest that the similarity of IL-1ß and IL6 levels in our experimental groups is due to the mechanism of action of ketamine on the immune system. More studies have to be carried out to explain this pathology. In conclusion, according to previous studies and considering the current study, we could suggest a prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.

In vivo and in vitro effects of fructose on rat brain acetylcholinesterase activity: an ontogenetic study.

Increased fructose concentrations are the biochemical hallmark of fructosemia, a group of inherited disorders on the metabolic pathway of this sugar. The main clinical findings observed in patients affected by fructosemia include neurological abnormalities with developmental delay, whose pathophysiology is still undefined. In the present work we investigated the in vitro and in vivo effects of fructose on acetylcholinesterase (AchE) activity in brain structures of developing rats. For the in vitro experiments, fructose was added at increasing concentrations to the incubation medium. It was observed that fructose provoked an inhibition of acetylcholinesterase activity in cerebral cortex of 30-day-old-rats, even at low concentrations (0.1 mM). For the in vivo experiments, rats were killed 1 h after a single fructose administration (5 µmol/g). Control group received the same volume of saline solution. We found that AchE activity was increased in cerebral cortex of 30- and 60-day-old rats receiving fructose administration. Finally, we observed that AchE activity was unaffected by acute fructose administration in cerebral cortex, striatum or hippocampus of 15- and 90-day-old rats. The present data suggest that a disruption in cholinergic homeostasis may be involved in the pathophysiology of brain damage observed in young patients affected by fructosemia.

Evaluation of acetylcholinesterase activity and behavioural alterations induced by ketamine in an animal model of schizophrenia.

OBJECTIVE: Cognitive deficits in schizophrenia play a crucial role in its clinical manifestation and seem to be related to changes in the cholinergic system, specifically the action of acetylcholinesterase (AChE). Considering this context, the aim of this study was to evaluate the chronic effects of ketamine in the activity of AChE, as well as in behavioural parameters involving learning and memory. METHODS: The ketamine was administered for 7 days. A duration of 24 h after the last injection, the animals were submitted to behavioural tests. The activity of AChE in prefrontal cortex, hippocampus and striatum was measured at different times after the last injection (1, 3, 6 and 24 h). RESULTS: The results indicate that ketamine did not affect locomotor activity and stereotypical movements. However, a cognitive deficit was observed in these animals by examining their behaviour in inhibitory avoidance. In addition, an increase in AChE activity was observed in all structures analysed 1, 3 and 6 h after the last injection. Differently, serum activity of AChE was similar between groups. CONCLUSION: Chronic administration of ketamine in an animal model of schizophrenia generates increased AChE levels in different brain tissues of rats that lead to cognitive deficits. Therefore, further studies are needed to elucidate the complex mechanisms associated with schizophrenia.

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.

Effects of sodium butyrate in animal models of mania and depression: implications as a new mood stabilizer.

Bipolar disorder is a severe mood disorder with high morbidity and mortality. Despite adequate treatment, patients continue to have recurrent mood episodes, residual symptoms, and functional impairment. Some preclinical studies have shown that histone deacetylase inhibitors may act on depressive-like and manic-like behaviors. Therefore, the aim of the present study was to evaluate the effects of sodium butyrate (SB) on behavioral changes in animal models of depression and mania. The animals were submitted to protocols of chronic mild stress or maternal deprivation for induction of depressive-like behaviors and subjected to amphetamine, or ouabain administration for induction of manic-like behaviors. SB reversed the depressive-like and manic-like behaviors evaluated in the animal models. From these results we can suggest that SB may be a potential mood stabilizer.

Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia.

Schizophrenia is one of the most disabling mental disorders that affects up to 1 % of the population worldwide. Although the causes of this disorder remain unknown, it has been extensively characterized by a broad range of emotional, ideational and cognitive impairments. Studies indicate that schizophrenia affects neurotransmitters such as dopamine, glutamate and acetylcholine. Recent studies suggest that rivastigmine (an acetylcholinesterase inhibitor) is important to improve the cognitive symptoms of schizophrenia. Therefore, the present study evaluated the protective effect of rivastigmine against the ketamine-induced behavioral (hyperlocomotion and cognitive deficit) and biochemical (increase of acetylcholinesterase activity) changes which characterize an animal model of schizophrenia in rats. Our results indicated that rivastigmine was effective to improve the cognitive deficit in different task (immediate memory, long term memory and short term memory) induced by ketamine in rats. Moreover, we observed that rivastigmina reversed the increase of acetylcholinesterase activity induced by ketamine in the cerebral cortex, hippocampus and striatum. However, rivastigmine was not able to prevent the ketamine-induced hyperlocomotion. In conslusion, ours results indicate that cholinergic system might be an important therapeutic target in the physiopathology of schizophrenia, mainly in the cognition, but additional studies should be carried.

Prenatal Stress Induces Long-Term Behavioral Sex-Dependent Changes in Rats Offspring: the Role of the HPA Axis and Epigenetics.

Preclinical genetic studies have related stress early exposures with changes in gene regulatory mechanisms, including epigenetic alterations, such as modifications of DNA methylation, histone deacetylation, and histones acetylation. This study evaluates the effects of prenatal stress on the behavior, hypothalamus-pituitary-adrenal (HPA)-axis, and epigenetic parameters in stressed dams and their offspring. The rats were subjected to a protocol of chronic unpredictable mild stress on the fourteenth day of pregnancy until the birth of offspring. After birth, maternal care was evaluated for six days. Following weaning, the locomotor and depressive-like behaviors of the dams and their offspring (60 days old) were assessed. The HPA axis parameters were evaluated in serum from dams and offspring, and epigenetic parameters (histone acetyltransferase (HAT), histone deacetylase (HDAC), DNA methyltransferase (DNMT) activities, and the levels of histone H3 acetylated at lysine residue 9 (H3K9ac) and histone 3 acetylated at lysine residue 14 (H3K14ac)) were assessed in dams' and offspring' brains. Prenatal stress did not significantly influence maternal care; however, it induced manic behavior in female offspring. These behavioral alterations in the offspring were accompanied by hyperactivity of the HPA-axis, epigenetic adaptations in the activity of HDAC and DNMT, and acetylation in the histones H3K9 and H3K14. In addition, the prenatal stressed female offspring showed increased levels of ACTH compared to their male counterpart. Our findings reinforce the impact of prenatal stress on behavior, stress response, and epigenetic profile of offspring.

Haloperidol alters neurotrophic factors and epigenetic parameters in an animal model of schizophrenia induced by ketamine.

This study aimed to evaluate Haloperidol's (Hal) effects on the behavioral, neurotrophic factors, and epigenetic parameters in an animal model of schizophrenia (SCZ) induced by ketamine (Ket). Injections of Ket or saline were administered intraperitoneal (once a day) between the 1st and 14th days of the experiment. Water or Hal was administered via gavage between the 8th and 14th experimental days. Thirty minutes after the last injection, the animals were subjected to behavioral analysis. The activity of DNA methyltransferase (DNMT), histone deacetylase (HDAC), and histone acetyltransferase and levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippocampus, and striatum. Ket increased the covered distance and time spent in the central area of the open field, and Hal did not reverse these behavioral alterations. Significant increases in the DNMT and HDAC activities were detected in the frontal cortex and striatum from rats that received Ket, Hal, or a combination thereof. Besides, Hal per se increased the activity of DNMT and HDAC in the hippocampus of rats. Hal per se or the association of Ket plus Hal decreased BDNF, NGF, NT-3, and GDNF, depending on the brain region and treatment regimen. The administration of Hal can alter the levels of neurotrophic factors and the activity of epigenetic enzymes, which can be a factor in the development of effect collateral in SCZ patients. However, the precise mechanisms involved in these alterations are still unclear.

Acetylcholinesterase activity in the rat brain after pneumococcal meningitis.

Pneumococcal meningitis is a life-threatening disease characterized by acute purulent infection of the meninges causing neuronal injury, cortical necrosis and hippocampal apoptosis. Cholinergic neurons and their projections are extensively distributed throughout the central nervous system. The aim of this study was to assess acetylcholinesterase activity in the rat brain after pneumococcal meningitis. In the hippocampus, frontal cortex and cerebrospinal fluid, acetylcholinesterase activity was found to be increased at 6, 12, 24, 48 and 96 hr without antibiotic treatment, and at 48 and 96 hr with antibiotic treatment. Our data suggest that acetylcholinesterase activity could be related to neuronal damage induced by pneumococcal meningitis.

Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats.

Non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine inhibit cytochrome C oxidase in mouse brain regions.

The highly active antiretroviral therapy completely changed the clinical evolution of HIV infection, reducing the morbidity and mortality among human immunodeficiency virus (HIV)-1 infected patients. Therefore, in the present study we evaluated the effect of chronic efavirenz (EFV) and nevirapine (NVP) administration on mitochondrial respiratory chain complexes activities (I, II, II-III, IV) in different brain regions of mice. Mice were orally administered via gavage with EFV 10 mg/kg, NVP 3.3 mg/kg or vehicle (controls) once a day for 36 days. We observed that the complex IV activity was inhibited by both EFV and NVP in cerebral cortex, striatum and hippocampus of mice, but not in cerebellum, as compared to control group. In contrast, chronic EFV and NVP administration did not alter complexes I, II and II-III. We speculated that brain energy metabolism dysfunction could be involved in the CNS-related adverse effects.

Behavioral and neurochemical effects of sodium butyrate in an animal model of mania.

The present study investigated the effect of the histone deacetylase inhibitor, sodium butyrate (SB), on locomotor behavior and on mitochondrial respiratory-chain complexes activity in the brain of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first treated with d-AMPH or saline (Sal) for 14 days. Thereafter, between days 8 and 14, rats were administered SB or Sal. In the prevention treatment, rats were treated with SB or Sal for 14 days and received d-AMPH or Sal between days 8 and 14. The d-AMPH treatment increased locomotor behavior in Sal-treated rats under reversion and prevention treatment, and SB reversed and prevented d-AMPH-related hyperactivity. Moreover, d-AMPH decreased the activity of mitochondrial respiratory-chain complexes in Sal-treated rats in the prefrontal cortex, hippocampus, striatum, and amygdala in both experiments, and SB was able to reverse and prevent this impairment. The present study suggests that the mechanism of action of SB involves induction of mitochondrial function in parallel with behavioral changes, reinforcing the need for more studies on histone deacetylase inhibitors as a possible target for new medications for bipolar disorder treatment.