Transcranial Direct Current Stimulation (tDCS) Promotes state-dependent Effects on Neuroinflammatory and Behavioral Parameters in rats Chronically Exposed to Stress and a Hyper-Palatable Diet.

Chronic stress is a common condition affecting health, often associated with unhealthy eating habits. Transcranial direct current stimulation (tDCS) has been proposed to address these issues. Thus, this research investigated the effects of tDCS on biometric, behavioral, and neurochemical parameters in chronically stressed rats fed a hyper-palatable cafeteria diet (CAFD). The study lasted 8 weeks, with CAFD exposure and/or chronic restraint stress model (CRS - 1 h/day, 5 days/week, for 7 weeks) started concurrently. tDCS or sham sessions were applied between days 42 and 49 (0.5 mA, 20 min/day). CAFD increased body weight, caloric consumption, adiposity, and liver weight. It also altered central parameters, reducing anxiety and cortical levels of IL-10 and BDNF. In turn, the CRS resulted in increased adrenals in rats with standard diet (SD), and anxiety-like and anhedonic behaviors in rats with CAFD. tDCS provided neurochemical shifts in CAFD-fed stressed rats increasing central levels of TNF-α and IL-10, while in stressed rats SD-fed induced a decrease in the adrenals weight, relative visceral adiposity, and serum NPY levels. These data demonstrated the anxiolytic effect of CAFD and anxiogenic effect of stress in CAFD-fed animals. In addition, tDCS promoted state-dependent effects on neuroinflammatory and behavioral parameters in rats chronically exposed to stress and a hyper-palatable diet. These findings provide primary evidence for additional mechanistic and preclinical studies of the tDCS technique for stress-related eating disorders, envisioning clinical applicability.

Transcranial direct current stimulation alters anxious-like behavior and neural parameters in rats with chronic pain exposed to alcohol.

The aim of this study was to evaluate the effects of transcranial direct current stimulation (tDCS) on anxiety-like behavior and neural parameters in rats with chronic pain exposed to alcohol. Thirty-six adult male Wistar rats were randomly assigned to control (CT), neuropathic pain (NP), NPtDCS, NP + alcohol (NPAL), or NPALtDCS groups, subjected to sciatic nerve chronic constriction injury (CCI) and exposed to alcohol (20% v/v solution, 4 g/kg) or vehicle by gavage for 15 days. Afterward, rats were treated using bimodal tDCS (0.5 mA/20 min/8 days) and tested in the open field. Rats were killed 24 h after the last behavioral assessment, and brain and spinal cord tissue samples were collected and processed for NPY immunohistochemistry, expression of Il1a and Il1b in the spinal cord, cerebellum, and hippocampus, and levels of IL-1α and IL-1ß in the same brain structures and the striatum. tDCS reverted the anxiety-like behavior induced by CCI and alcohol, and the increased expression of Il1a in the spinal cord induced by alcohol, which increased the expression of Il1b in the cerebellum. In addition, tDCS modulated the hypothalamic NPY-immunoreactivity, increased the levels of IL-1α in the hippocampus (like NP and AL), and increased the expression of Il1b in the spinal cord (like AL). Thus, this study shows that tDCS changes NP and alcohol-induced anxiety-like behavior, possibly through its central modulatory effect of NPY and spinal cord expression of Il1a and Il1b, being considered a treatment option for alcohol and NP-induced anxiety symptoms.

Bimodal transcranial direct current stimulation reduces alcohol consumption and induces long-term neurochemical changes in rats with neuropathic pain.

This study aimed to evaluate the effects of repeated bimodal transcranial direct current stimulation (tDCS) on alcohol consumption and immunohistological and neurochemical parameters in nerve-injured rats. Forty-eight adult male Wistar rats were distributed into six groups: control, neuropathic pain (NP) + sham-tDCS, NP + alcohol + sham-tDCS, alcohol + sham-tDCS, alcohol + tDCS, and NP + alcohol + tDCS. NP is induced by chronic sciatic nerve constriction (CCI). The rats were exposed to a 10% alcohol solution by voluntary consumption for 14 days. From the 16th day after surgery, bimodal tDCS was applied for 20 min/day for 8 days. Brain structures were collected to evaluate the number of neuropeptide Y (NPY)-positive neurons, neurites, and argyrophilic grains by immunohistochemistry, and brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), interleukin (IL)-6, and IL-10 by ELISA. Nerve-injured rats showed a progressive increase in alcohol consumption compared to the non-injured rats. In addition, there was a reduction in voluntary alcohol consumption over time induced by tDCS. Alcohol exposure, chronic pain, and tDCS treatment modulated the central NPY immunoreactivity. tDCS increased the cerebellar levels of IL-6 and IL-10, and CCI and/or tDCS reduced striatal BDNF levels. The current data suggest that tDCS could be a promising non-pharmacological adjuvant to treat patients with chronic pain who use alcohol to relieve their symptoms.

Single exercise stress reduces central neurotrophins levels and adenosine A1 and A2 receptors expression, but does not revert opioid-induced hyperalgesia in rats.

BACKGROUND: This study assessed the effects of an acute stress model upon the long-term hyperalgesia induced by repeated morphine administration in neonatal rats. We also evaluated neurotrophins and cytokines levels; expressions of adenosine and acetylcholine receptors, and acetylcholinesterase enzyme at the spinal cord. MATERIAL AND METHODS: Male Wistar rats were subjected to morphine or saline administration from P8 to P14. Thermal hyperalgesia and mechanical hyperesthesia were assessed using the hot plate (HP) and von Frey (vF) tests, respectively, at postnatal day P30 and P60. After baseline measurements, rats were subjected to a single exercise session, as an acute stress model, at P30 or P60. We measured the levels of BDNF and NGF, interleukin-6, and IL-10 in the cerebral cortex and the brainstem; and the expression levels of adenosine and muscarinic receptors, as well as acetylcholinesterase (AChE) enzyme at the spinal cord. RESULTS: A stress exercise session was not able to revert the morphine-induced hyperalgesia. The morphine and exercise association in rats induced a decrease in the neurotrophins brainstem levels, and A1 , A2A , A2B receptors expression in the spinal cord, and an increase in the IL-6 cortical levels. The exercise reduced M2 receptors expression in the spinal cord of naive rats, while morphine prevented this effect. CONCLUSIONS: Single session of exercise does not revert hyperalgesia induced by morphine in rats; however, morphine plus exercise modulate neurotrophins, IL-6 central levels, and expression of adenosine receptors.

Maternal Deprivation and Sex Alter Central Levels of Neurotrophins and Inflammatory Cytokines in Rats Exposed to Palatable Food in Adolescence.

Maternal deprivation (MD) in rodents is used to simulate human-infant early life stress, which leads to neural, hormonal, and behavioral alterations. Palatable food (PF) can reduce the stress response, and individuals use it as a self-applied stress relief method. Thus, the present study aimed to evaluate the effect of the association between MD in the early life (P1-P10) and PF consumption (condensed milk, P21-P44) in the central neuroplasticity (BDNF/NGF levels) and central neuroinflammatory parameters (TNF-α, IL-6, and IL-10 levels) in male and female Wistar rats in the adolescence. In addition, weight-related parameters (weight gain, Lee Index, and relative adipose tissue weight) were evaluated. PF exposure increased relative adipose tissue weight; however, it did not lead to a change in animals' body weight. MD reduced hypothalamic BDNF and NGF levels, and hippocampal TNF-α levels in male and female rats. Animals of both sexes that received PF, exhibited reduced hypothalamic NGF levels. Neuroinflammatory marker evaluations showed that male rats were more susceptible to the interventions than female rats, since MD reduced their cortical IL-10 levels and PF increased their IL-6 levels. Differences in the Lee index, central BDNF, TNF-α, and IL-6levels were observed between sexes. Male animals per se presented greater Lee index. Female rats had higher BDNF and IL-6 levels in the hippocampus and hypothalamus and higher hypothalamic TNF-α levels than those observed in males. In conclusion, there were more noticeable effects of MD than PF on the variables measured in this study. Sex effect was identified as an important factor and influenced most of the neurochemical measures in this study. In this way, we suggest including both female and male animals in researches to improve the quality of translational studies.

Maternal deprivation alters nociceptive response in a gender-dependent manner in rats.

The present study aimed at investigating both the early and long-term effects of maternal deprivation as well as gender on neuromotor reflexes, anxiety behavior and thermal nociceptive responses. A total of 64 Wistar rats pups (32 males, 32 females) were utilized and were deprived of their mother for 3 h/daily, from postnatal day 1 (P1) until P10. Successively, animals were divided into 2 groups: control group (C) - pups no subjected to intervention; and the maternal-deprived group (MD): pups subjected to maternal deprivation. The neuromotor reflexes were evaluated through the righting reflex and negative geotaxis tests; the exploratory behavior by open field test (OFT); the anxiety-like behavior by elevated plus-maze test (EPM); the thermal nociceptive responses byhot plate (HP) and tail-flick (TFL) tests. All the animals subjected to maternal deprivation showed a delayed reflex response at P8 in the negative geotaxis test. In contrast, the OFT at P20 identified an effect of gender on the outer crossings and grooming as well as an interaction between gender and maternal deprivation on latency. Additionally, effect of maternal deprivation in the open and closed arms as well as gender effect in the protected head-dipping (PHD) and non-protected head-dipping (NPHD) were observed at P20 (EPM). In contrast, there were a gender effect on latency and an interaction between gender and maternal deprivation on rearing at P42. Moreover, in nociceptive tests was observed an analgesic effect induced by maternal deprivation; however, in the TFL test, only deprived females showed this effect. Surprisingly, only control animals presented an ontogeny nociceptive effect in the HP testat P21 and P43, which may be related to an increase in the inhibitory nociceptive pathways throughout life. In this way, we suggest maternal deprivation to be able to anticipate the maturation of the inhibitory nociceptive pathway. In conclusion, maternal deprivation induced a delayed reflex response at P8 and altered the anxiety and nociceptive behaviors according to the time after exposure to this stressor, in a gender-specific manner.

Transcranial direct current stimulation (tDCS) and trigeminal pain: A preclinical study.

OBJECTIVE: Our objective was to evaluate the Transcranial direct current stimulation (tDCS) effect on facial allodynia induced by chronic constriction of the infraorbital nerve (CCI-ION) and on the brainstem levels of TNF-α, NGF, IL-10, and serum LDH in rats. METHODS: Rats were exposed to the CCI-ION model. Facial allodynia was assessed by von Frey filaments test at baseline, 3, 7, 10, and 14 days postsurgery and 24 hr and 7 days after the bimodal tDCS sessions for 20 min/day/8 days. RESULTS: Chronic constriction of the infraorbital nerve induced a significant decrease in the mechanical threshold 14 days after surgery. This effect was reversed by tDCS treatment, with the mechanical threshold returning to basal levels at 24 hr after the end of the treatment and it persisted for 7 days after the end of the treatment. tDCS also decreased LDH serum levels compared to those in the control group. There was an interaction between pain and treatment with respect to brainstem levels of NGF, TNF-α, and IL-10. CONCLUSION: Chronic constriction of the infraorbital nerve model was effective in establishing trigeminal neuropathic pain on 14 days after surgery, and tDCS reduced allodynia and LDH serum levels and promoted alterations in NGF, TNF-α, and IL-10 brainstem levels. Thus, we suggest that tDCS may be a potential therapy in the trigeminal pain treatment.

Transcranial direct current stimulation (tDCS) modulates biometric and inflammatory parameters and anxiety-like behavior in obese rats.

Obesity is a multifactorial disease associated with metabolic dysfunction and the prevention and treatment of obesity are often unsatisfactory. Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique that has proven promising in the treatment of eating disorders such as obesity. We investigate the effects of tDCS on locomotor and exploratory activities, anxiety-like and feeding behavior, and levels of brain-derived neurotrophic factor (BDNF), IL (interleukin)-10, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in the cerebral cortex of obese rats. A total of 40 adult male Wistar rats were used in our study. Animals were divided into groups of three or four animals per cage and allocated to four treatment groups: standard diet plus sham tDCS treatment (SDS), standard diet plus tDCS treatment (SDT), hypercaloric diet plus sham tDCS treatment (HDS), hypercaloric diet plus tDCS treatment (HDT). After 40 days on a hypercaloric diet and/or standard diet were to assessed the locomotor and exploratory activity and anxiety-like behavior to by the open field (OF) and elevated plus maze (EPM) tests respectively before and after exposure to tDCS treatment. The experimental groups were submitted to active or sham treatment tDCS during eight days. Palatable food consumption test (PFT) was performed 24 h after the last tDCS session under fasting and feeding conditions. Obese animals submitted to tDCS treatment showed a reduction in the Lee index, visceral adipose tissue weight, and food craving. In addition, bicephalic tDCS decreased the cerebral cortex levels of IL-1ß and TNF-α in these animals. Exposure to a hypercaloric diet produced an anxiolytic effect, which was reversed by bicephalic tDCS treatment. These results suggest that, in accordance with studies in humans, bicephalic tDCS could modulate biometric and inflammatory parameters, as well as anxiety-like and feeding behavior, of rats subjected to the consumption of a hypercaloric diet.

Morphine exposure and maternal deprivation during the early postnatal period alter neuromotor development and nerve growth factor levels.

The objective of this study was to verify whether repeated morphine administration and maternal deprivation in early life alter neurobehavioral development and central nerve growth factor (NGF) levels. A total of 58 male Wistar rat pups were used in our study. From postnatal day 1 (P1), litters were daily deprived of their mother for 3h; this was continued for the first 10days of life. Animals were divided into 5 groups: total control (C), did not receive any intervention; saline (S), received saline solution; morphine (M), received morphine; deprived-saline group (DS), were subjected to maternal deprivation and received saline solution; and deprived-morphine (DM), were subjected to maternal deprivation and received morphine. From P8, newborns received subcutaneous (s.c.) injections of morphine or saline (5µg) once daily for 7days. Righting reflex, negative geotaxis and gait were chosen as postural parameters to evaluate neuromotor reflexes. In the righting reflex test, a delay in the development of animals was evidenced in the M group. Performance of negative geotaxis was slower in the M and DM groups. In the gait test, all groups showed a daily improvement in performance in terms of locomotion frequency. An increased frequency of rearing was observed in the M, DS, and DM groups from P16 to P20. The DM group presented an increase in NGF levels in the brainstem. An increase in cerebral cortex NGF levels in the M, DS, and DM groups was observed as well. Our results suggest that changes in environmental conditions and the disruption of mother-infant interactions during the neonatal period can produce changes in the neurobiology, physiology, and emotional behavior of rats. This finding has important implications for the maternal-neonate interaction needed for normal brain development in newborns.

Increased Oxidative Parameters and Decreased Cytokine Levels in an Animal Model of Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous disorder characterized by impairing levels of hyperactivity, impulsivity and inattention. Oxidative and inflammatory parameters have been recognized among its multiple predisposing pathways, and clinical studies indicate that ADHD patients have increased oxidative stress. In this study, we aimed to evaluate oxidative (DCFH oxidation, glutathione levels, glutathione peroxidase, catalase and superoxide dismutase activities) and inflammatory (TNF-α, IL-1ß and IL-10) parameters in the most widely accepted animal model of ADHD, the spontaneously hypertensive rats (SHR). Prefrontal cortex, cortex (remaining regions), striatum and hippocampus of adult male SHR and Wistar Kyoto rats were studied. SHR presented increased reactive oxygen species (ROS) production in the cortex, striatum and hippocampus. In SHR, glutathione peroxidase activity was decreased in the prefrontal cortex and hippocampus. TNF-α levels were reduced in the prefrontal cortex, cortex (remaining regions), hippocampus and striatum of SHR. Besides, IL-1ß and IL-10 levels were decreased in the cortex of the ADHD model. Results indicate that SHR presented an oxidative profile that is characterized by an increase in ROS production without an effective antioxidant counterbalance. In addition, this strain showed a decrease in cytokine levels, mainly TNF-α, indicating a basal deficit. These results may present a new approach to the cognitive disturbances seen in the SHR.

Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats.

Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd.

Morphine exposure during early life alters thermal and mechanical thresholds in rats.

BACKGROUND: Morphine is an opioid analgesic used to relieve moderate-to-severe pain, including pain in neonates at the intensive care unit. In our previous study, we showed that repeated morphine exposure during early life could trigger long-lasting implications on the developing nervous system, such as long-term neurochemical and behavioral alterations in adult rats. AIMS: The aim of our study was to determine the short-, intermediate-, and long-term effects of repeated morphine administration during early life on the thermal and mechanical thresholds and on the central levels (cerebral cortex and brainstem) of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and cytokines (interleukin-6 [IL-6] and IL-10). METHODS: Male Wistar rats were administered morphine (5µg/day, s.c.) or saline for 7days from postnatal day 8 (P8) until P14. The nociceptive effect was assessed by evaluating the thermal response using the hot plate test (HPT) and the mechanical response by Von Frey (VFT) and Randall-Selitto (RST) tests at P16, P30, and P60. BDNF, NGF, IL-6, and IL-10 levels were measured in the cerebral cortex and brainstem. RESULTS: In HPT, no difference in latency was observed at P16; however, at P30 and P60, the morphine-treated group exhibited a less increase in the nociceptive threshold compared to the saline group. VFT and RST demonstrated an interaction between group and age, where the morphine group showed a less pronounced increase in latency with age, which is indicative of allodynia. In the cerebral cortex, an association between BDNF and NGF levels and age was observed, where neurotrophin level increased with age in the saline group, and decreased with age in the morphine group. In addition, IL-10 levels decreased with age in both groups; however, there was no significant difference in IL-6 levels. In the brainstem, BDNF, NGF, IL-6, and IL-10 levels increased with age. DISCUSSION: Repeated morphine exposure during neonatal life triggered alterations in the nociceptive behavior, including thermal hyperalgesia and mechanical allodynia, as well as decreased levels of BDNF and NGF in the cerebral cortex. Our study highlights the importance of extensive comprehension of the pharmacological interventions during CNS maturation.

Cafeteria diet increases liquid intake and serum creatinine levels in rats

Introduction: Important changes in human dietary pattern occurred in recent decades. Increased intake of processed foods leads to obesity, which is related with the development of chronic diseases such as type 2 diabetes mellitus, hypertension, as well as cardiovascular and chronic kidney diseases. The prevalence of hypertension has also dramatically increased in recent years, and high sodium intake contributes to this scenario. In healthy individuals, kidneys are the primary end-organs that regulate sodium homeostasis. This study aims to evaluate renal function parameters and systolic blood pressure measurements in an animal model of obesity. Methods: Sixty-day-old male Wistar rats (n=30) were divided into two groups: standard (SD) and cafeteria diet (CD). Cafeteria diet was altered daily and was composed by crackers, wafers, sausages, chips, condensed milk, and soda. All animals had free access to water and chow and the experiment was carried out for 6 weeks. Weight gain, sodium and liquid intake control, systolic blood pressure measurements, and renal function parameters were evaluated. Results: Animals exposed to cafeteria diet had an increase of 18% in weight compared to the control group. Sodium intake was increased by cafeteria diet and time (F(1,28)=773.666, P=0.001 and F(5,28)=2.859, P=0.02, respectively) and by the interaction of both factors (F(6,28)=2.859, P=0.02). On liquid intake occurred only effect of cafeteria diet and time (F(1,28)=147.04, P=0.001 and F(5,28)=3.996, P=0.003, respectively). Cafeteria diet exposure also induced an increase on creatinine serum levels (P=0.002), however this effect was not observed on creatinine urine levels (P>0.05) nor on systolic pressure measurements (Students' t test, P>0.05). Conclusions: Obesity induced by cafeteria diet exposure increases liquid intake and alters creatinine serum levels, an important renal function marker. Considering the high consumption of hypercaloric food currently in the world, further studies are required to elucidate the modifications on renal function triggered by this diet over time (AU)

Evaluation of different procedure involved in the Transcranial Direct Current Stimulation (tDCS) technique experimental application

Introduction: The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in the central nervous system of animals and humans. Furthermore, tDCS has been suggested as a therapeutic tool for pain management. The aim of this study was to standardize a non-invasive tDCS technique indexed by the nociceptive response of rats submitted to different conditions necessary to the tDCS application. Method: 60-day-old male Wistar rats (n=65), divided into 6 groups: control(C); non-active sham (NAS); active-sham (AS); active-sham restrained (ASR); non-active sham restrained (NASR); active tDCS treatment. Animals received treatment during 30 seconds (sham-active) or 20 minutes (restraint and tDCS)/8 days. Nociceptive threshold was assessed by Hot Plate test at baseline, immediately and 24h after the first session, immediately and 24h after the last session. Variance analysis of repeated measurements followed by Bonferroni was performed for intra-group comparison. Results: Physical restraint and 30 seconds stimulation (sham-tDCS) increased pain sensitivity (P≤0.05), and tDCS treatment was able to prevent the thermal hyperalgesia. Our original tDCS montage is similar to that used in the procedure with humans, because it is not an invasive technique. The electrodes are positioned on the head, and the animals are immobilized during the 20-minute treatment. As this procedure could involve behavior and neurochemical alterations due to stress induced by restriction (thus, it creates a research bias), we hypothesized that a 30-second electrical stimulus application (sham-tDCS) and the physical restriction used during tDCS treatment might alter nociceptive response in rats. Conclusion: There are methodological limitations in the present tDCS-technique. Although active-tDCS treatment is able to prevent these harmful effects, interference of these factors has to be considered during the results' analysis. Future adaptations of the tDCS-technique in rats are required to evaluate its therapeutic effects (AU)

Melatonin as a potential counter-effect of hyperalgesia induced by neonatal morphine exposure.

Morphine administration in the neonatal period can induce long-term effects in pain circuitry leading to hyperalgesia induced by the opioid in adult life. This study explored a new pharmacological approach for reversing this effect of morphine. We focused on melatonin owing its well-known antinociceptive and anti-inflammatory effects, and its ability to interact with the opioid system. We used the formalin test to assess the medium and long-term effects of melatonin administration on hyperalgesia induced by morphine in early life. Newborn rats were divided into two groups: the control group, which received saline, and the morphine group, which received morphine (5µg subcutaneously [s.c.]) in the mid-scapular area, once daily for 7days, from P8 (postnatal day 8) until P14. At postnatal days 30 (P30) and 60 (P60), both groups were divided in two subgroups, which received melatonin or melatonin vehicle 30min before the formalin test. The nociceptive responses were assessed by analyzing the total time spent biting, flicking, and licking the formalin-injected hind paw; these responses were recorded during the first 5min (neurogenic/acute phase) and from 15 to 30min (inflammatory/tonic phase). Initially, animals in the morphine/vehicle group showed increased nociceptive behavior in phase II (inflammatory) of the formalin test at P30, and in the neurogenic and inflammatory phases at P60. These increased nociceptive responses were fully reversed by melatonin administration at either age. These findings show that melatonin administration is a potential means for countering hyperalgesia induced by neonatal morphine exposure in young and adult rats.

Melatonin Alters the Mechanical and Thermal Hyperalgesia Induced by Orofacial Pain Model in Rats.

Melatonin is a neuroendocrine hormone that presents a wide range of physiological functions including regulating circadian rhythms and sleep, enhancing immune function, sleep improvement, and antioxidant effects. In addition, melatonin has received special attention in pain treatment since it is effective and presents few adverse effects. In this study, we evaluated the effect of acute dose of melatonin upon hyperalgesia induced by complete Freund's adjuvant in a chronic orofacial pain model in Sprague-Dawley rats. Nociceptive behavior was assessed by facial Von Frey and the hot plate tests at baseline and thereafter 30, 60, and 120 min, 24 h, and 7 days after melatonin treatment. We demonstrated that acute melatonin administration alters mechanical and thermal hyperalgesia induced by an orofacial pain model (TMD), highlighting that the melatonin effect upon mechanical hyperalgesia remained until 7 days after its administration. Besides, we observed specific tissue profiles of neuroimmunomodulators linked to pain conditions and/or melatonin effect (brain-derived neurotrophic factor, nerve growth factor, and interleukins 6 and 10) in the brainstem levels, and its effects were state-dependent of the baseline of these animals.

The Influence of Palatable Diets in Reward System Activation: A Mini Review.

The changes in eating patterns that have occurred in recent decades are an important cause of obesity. Food intake and energy expenditure are controlled by a complex neural system involving the hypothalamic centers and peripheral satiety system (gastrointestinal and pancreatic hormones). Highly palatable and caloric food disrupts appetite regulation; however, palatable foods induce pleasure and reward. The cafeteria diet is such a palatable diet and has been shown consistently to increase body weight and induce hyperplasia in animal obesity models. Moreover, palatable high-fat foods (such as those of the cafeteria diet) can induce addiction-like deficits in brain reward function and are considered to be an important source of motivation that might drive overeating and contribute to the development of obesity. The mechanism of neural adaptation triggered by palatable foods is similar to those that have been reported for nondrug addictions and long-term drug use. Thus, this review attempts to describe the potential mechanisms that might lead to highly palatable diets, such as the cafeteria diet, triggering addiction, or compulsion through the reward system.

Hypoestrogenism alters mood: Ketamine reverses depressive-like behavior induced by ovariectomy in rats.

BACKGROUND: Estrogen deficiency is associated with the onset of depressive and anxiety symptoms, cognitive impairment, and adverse consequences. We investigated depressive-like behaviors in ovariectomized rats and ketamine's effect on this behavior. METHODS: Twenty-eight female Wistar adult rats were initially divided into two groups: ovariectomized (OVX) and sham surgery (SHAM). Hormonal status was verified by vaginal cytology, and the rats were subjected to a forced swimming (FS) test 18 days post-surgery, an open field (OF) test 28 days post-surgery, and an elevated plus maze (EPM) test 38 days post-surgery (Experiment 1). In addition, the effect of ketamine on depressive-like behavior of the female rats was evaluated (Experiment 2). RESULTS: OVX group exhibited anxiety-like behavior on EPM test (lower time spent and fewer entries in the open arms), without any difference in performance in the OF test. OVX rats showed depressive-like behavior (higher time of immobility) than SHAM rats in FS test. The SHAM group showed signs of hypoestrogenism (anestrus) at six months of age. Moreover, ketamine was able to reverse depressive-like behavior in the FS retest in both groups (OVX and SHAM). CONCLUSION: Similar to the literature, we showed the antidepressant effect of ketamine in depressive female rats which was induced by ovariectomy; including in female rats submitted to sham surgery that interestingly presented a premature menopausal.

Obesity and Hyperlipidemia Modulate Alveolar Bone Loss in Wistar Rats.

BACKGROUND: A positive association between obesity-associated metabolic disorders (e.g., hyperlipidemia and diabetes) and periodontitis has been demonstrated in the literature. This study evaluates the role of cafeteria diet-induced obesity/hyperlipidemia (CAF) on alveolar bone loss (ABL) in rats. METHODS: Sixty male Wistar rats were randomly divided in four groups: control, periodontitis (PERIO), obesity/hyperlipidemia (CAF), and obesity/hyperlipidemia plus periodontitis (CAF+PERIO). Groups CAF and CAF+PERIO were exposed to a high-fat, hypercaloric diet. At week 12, periodontal disease was induced in groups PERIO and CAF+PERIO by ligatures in the upper second molar. The contralateral tooth was considered the intragroup control. Body weight and Lee index were evaluated weekly during the experiment. Serum glucose and cholesterol/triglycerides in the liver were evaluated, and percentage of ABL was measured by microcomputed tomography. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were evaluated by enzyme-linked immunosorbent assay at week 17. RESULTS: Body weight, Lee index, and cholesterol/triglycerides in the liver increased in groups exposed to the cafeteria diet. Groups PERIO and CAF+PERIO exhibited a significantly higher ABL compared to control and CAF groups. The presence of obesity and hyperlipidemia significantly increased ABL in the CAF+PERIO group compared to the PERIO group (53.60 ± 3.44 versus 42.78 ± 7.27, respectively) in the sides with ligature. Groups exposed to CAF exhibited higher ABL in the sides without ligature. No differences were observed among groups for IL-1ß and TNF-α. CONCLUSION: Obesity and hyperlipidemia modulate the host response to challenges in the periodontium, increasing the expression of periodontal breakdown.

Hypercaloric diet modulates effects of chronic stress: a behavioral and biometric study on rats.

Obesity is a chronic disease that has been associated with chronic stress and hypercaloric diet (HD) consumption. Increased ingestion of food containing sugar and fat ingredients (comfort food) is proposed to "compensate" chronic stress effects. However, this eating habit may increase body fat depositions leading to obesity. This study evaluated behavioral/physiological parameters seeking to establish whether there is an association between the effects of HD intake and stress, and to test the hypothesis that the development of anxious behavior and obesity during chronic stress periods depends on the type of diet. Sixty-day-old male Wistar rats (n = 100) were divided into four groups: standard chow, hypercaloric diet, chronic stress/standard chow and chronic stress/hypercaloric diet. Chronic stress was induced by restraint stress exposure for 1 h/day, for 80 d. At the end of this period, rat behavior was evaluated using open-field and plus-maze tests. The results showed that HD alone increased weight gain and adipose deposition in subcutaneous and mesenteric areas. However, stress reduced weight gain and adipose tissue in these areas. HD also increased naso-anal length and concurrent stress prevented this. Behavioral data indicated that stress increased anxiety-like behaviors and comfort food reduced these anxiogenic effects; locomotor activity increased in rats fed with HD. Furthermore, HD decreased corticosterone levels and stress increased adrenal weight. The data indicate that when rats are given HD and experience chronic stress this association reduces the pro-obesogenic effects of HD, and decreases adrenocortical activity.