Behavior In Adult Male Rats Research Articles

Impact of temporomandibular disorder on food preference behavior in adult male rats

ObjectiveTemporomandibular disorders (TMD) are a group of conditions affecting the jaw, surrounding muscles and associated structures. Researches indicate that TMD has implications for changes in nutritional behavior. This study investigates the impact of TMD on the food preference behavior of rats, examining various food models with differing caloric content, taste, and texture. DesignForty-two male Wistar rats (200–250 g) were divided into six groups, comprising three control and three pain or TMD groups. Induction of TMD by injection of complete Freund adjuvant (CFA) into the left temporomandibular joint (TMJ) of rat serves as a model for studying TMD. Twenty-four hours post-TMD induction, the preference of animals to foods with differences in calories, taste and texture was evaluated with the help of an automatic preference measuring device. ResultsIn terms of caloric preferences, the pain group exhibited a distinct shift towards high-calorie food. Taste preferences were marked by an increased preference for sweet food in the pain group. Texture preferences were altered, with the pain group displaying a preference for low-texture food. ConclusionTMD in rats leads to increased preferences for high-calorie and sweet foods, as well as altered preferences for food textures. These findings highlight the influence of TMJ pain on food preference behavior in rats.

The Projection-Specific Noradrenergic Modulation of Perseverative Spatial Behavior in Adult Male Rats.

Adaptive behavior relies on efficient cognitive control. The anterior cingulate cortex (ACC) is a key node within the executive prefrontal network. The reciprocal connectivity between the locus ceruleus (LC) and ACC is thought to support behavioral reorganization triggered by the detection of an unexpected change. We transduced LC neurons with either excitatory or inhibitory chemogenetic receptors in adult male rats and trained rats on a spatial task. Subsequently, we altered LC activity and confronted rats with an unexpected change of reward locations. In a new spatial context, rats with decreased noradrenaline (NA) in the ACC entered unbaited maze arms more persistently which was indicative of perseveration. In contrast, the suppression of the global NA transmission reduced perseveration. Neither chemogenetic manipulation nor inactivation of the ACC by muscimol affected the rate of learning, possibly due to partial virus transduction of the LC neurons and/or the compensatory engagement of other prefrontal regions. Importantly, we observed behavioral deficits in rats with LC damage caused by virus injection. The latter finding highlights the importance of careful histological assessment of virus-transduced brain tissue as inadvertent damage of the targeted cell population due to virus neurotoxicity or other factors might cause unwanted side effects. Although the specific role of ACC in the flexibility of spatial behavior has not been convincingly demonstrated, our results support the beneficial role of noradrenergic transmission for an optimal function of the ACC. Overall, our findings suggest the LC exerts the projection-specific modulation of neural circuits mediating the flexibility of spatial behavior.

Orexin-1 Receptor Antagonist SB-334867 Enhances Formalin-Induced Nociceptive Behaviors in Adult Male Rats.

Orexin (hypocretin) is one of the hypothalamic neuropeptides that plays a critical role in some behaviors including feeding, sleep, arousal, reward processing, and drug addiction. Neurons that produce orexin are scattered mediolaterally within the Dorsomedial Hypothalamus (DMH) and the lateral hypothalamus. In the current research, we assessed the impact of prolonged application of the antagonist of Orexin Receptor 1 (OXR1) on nociceptive behaviors in adult male rats. Sixteen Wistar rats received subcutaneous (s.c.) injections of the OXR1 antagonist, SB-334867 (20 mg/kg, i.p.), or its vehicle repetitively from Postnatal Day 1 (PND1)-PND30. On the 30th day following the final application of the OXR1 antagonist formalin-provoked pain was evaluated by injecting formalin. Administration of the OXR1 antagonist in the long-term augmented the formalin-provoked nociceptive behaviors in interphase and phase II of the formalin-induced pain. Current results showed that the continued inhibiting OXR1 might be implicated in formalin-induced nociceptive behaviors. Therefore, the present study highlighted the effect of orexin on analgesia.

TRPM2 may be involved in high fructose corn syrup-induced anxiety-like behavior in adult male rats.

Excessive high fructose corn syrup (HFCS) consumption is known to cause oxidative stress, which induces transient receptor potential melastatin type 2 (TRPM2) channel gating. Oxidative stress-induced TRPM2 gating is suggested to play an important role in neurons, indicating a role for the TRPM2 channel in a variety of neuropsychiatric disorders including depression and anxiety. We investigated the effects of HFCS and chronic immobilization stress (CIS) on TRPM2 channel immunoreactivity, anxiety, and depressive-like behaviors in adult male rats. The male rats (n=8/group) were divided into 4 groups: Control, 20% HFCS (F20), 40% HFCS (F40), and stress. The control group received tap water, and F20 and F40 groups were exposed to HFCS 20% and 40% respectively for 14 consecutive days. Rats in the stress group were subjected to immobilization stress for 3 or 6 hours daily in the first and second weeks to induce CIS. Then, light/dark tests, open field tests (OFT), and tail suspension tests (TST) were performed, respectively. In the light/dark test, the time spent in the dark chamber significantly increased in all groups vs the control group (P<0.01). In support of this result, time spent in the light chamber significantly decreased in all groups vs the control group (P<0.01). Besides, CIS significantly increased depressive-like behavior in the stress group vs the control group (P<0.05). In serum hormone levels, corticosterone (CORT) levels significantly increased in the F40 and stress groups vs the control group (P<0.01). TRPM2 immunoreactivity significantly increased in the hippocampus, prefrontal cortex (PFC), nucleus accumbens (NaC), and amygdala regions by HFCS and CIS treatments. For the first time in the present study, showed that f increased immunoreactivity of the TRPM2 cation channels may be linked to the anxiety-like behavior induced by HFCS.

Analyzing the adverse effects of childhood stress on adult anxiety behaviors by testing on male rats and addressing it with a period of aerobic exercise during adolescence

Anxiety is one of the most common diagnoses in psychiatry, which is twice as common in women as in men. Anxiety and depression disorders are significant because they affect a person's social and individual functioning and lead to severe economic and social damage, so they are expected to be debilitating diseases worldwide in the coming years. Considering the importance of treating stress disorders such as anxiety, which improves patients' social and personal functioning, and taking into account the side effects of drugs, researchers proposed sports activities as a non-pharmacological and effective occupational therapy method. But it is not clear whether the effects of exercise can be related to the regulation of the serotonergic system in the brain (especially anxiety behavior). Therefore, this research was designed and carried out to answer the following question: Will doing optional exercise (Running Wheel) and not mandatory exercise (Treadmill exercise) during adolescence be able to improve the ill effects of MS? In this research, six pregnant mice were used. After giving birth, their babies experienced the stress of separation from their mother for 12 days between the 2nd and 14th days after birth, and then from the 28th day, they exercised with the Running Wheel for a month. The number of rats was 8 for behavioral tests and 4 for molecular tests. In the model implemented in this research, after birth, mouse babies are separated from their mother for 180 minutes every day for 12 days (from the second day of birth to the 14th day after birth) and placed in a separate cage. This protocol is so-called. It is called Maternal Neonatal Separation or childhood stress. The results of this research determined that childhood stress in the form of separation from the mother is capable of causing anxiety behaviors in adult male rats. On the other hand, the results of this research determined that optional exercise with running wheels during adolescence can reduce the adverse effects of stress and anxiety-related behaviors.

Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats

Mood disorders, including anxiety and depression caused by prenatal ethanol exposure (PE) are prevalent conditions in fetal alcohol spectrum disorders (FASDs). Prenatal ethanol exposure is associated with persistent dysfunctions of several neurotransmitter systems, including the serotonin (5-HT) system, which plays a major role in mood regulation and stress homeostasis. While PE is known to disrupt the development of the 5-HT system, the cellular mechanisms by which it alters the function of dorsal raphe nucleus (DRn) 5-HT neurons and their synaptic inputs remain unknown. Here, we used a second-trimester binge-drinking pattern PE (two daily gavages of 15% w/v ethanol at 3 g/kg, 5–6 h apart) during gestational days 8 - 20 and measured anxiety-like behaviors of adult male rats using the elevated plus (EPM) and zero (ZM) mazes. We also employed ex-vivo electrophysiological and pharmacological approaches to unravel the mechanisms by which PE alters the excitability and synaptic transmission onto DRn 5-HT neurons. We found that PE enhanced anxiety-like behaviors in adult male rats and induced a persistent activation of DRn 5-HT neurons. The PE-induced activation of DRn 5-HT neurons was largely mediated by potentiation of DRn glutamate synapses, which was caused by activation of the nitrergic system and impaired endocannabinoid signaling. As such, the present study reveals “push-pull” effects of PE on nitrergic and eCB signaling, respectively, which mediate the enhanced activity of DRn 5-HT neurons and could contribute to anxiety-like behaviors observed in animal model of FASD.

The Effects of Alcohol and Social Isolation on Yawning Behavior in Adult Male Rats, Treated with Opioid Receptor Agonist and Antagonist

The number of 88 rats was chosen, after 21 days, they were ablactated and categorized them as following groups:&#x0D; The control group 1 has a cage of 8 rats in a social condition. After 6 weeks of saline injection (1mg / kg), the yawning behavior is recorded for 60 minutes. Group 2 in social conditions of receiving ethanol for 2 months, each serving of 600 mg / kg. Group 3 social isolation without treatment with agonist and antagonist, Opioid and alcohol drugs in a separate cage, each cage has one rat. After 6 weeks, It is recorded the yawning was cured for 60 minutes. Group 4 social isolation for 6 weeks and then treatment with alcohol agonist (1200 mg / kg) after 30 minutes of yawing behavior is recorded for 60 minutes. Group 5 Social isolation after 6 weeks of treatment with opioid drugs (5mg / kg of morphine) after 30 minutes of yawing behavior is recorded for 60 minutes. Group 6 social isolation after 6 weeks of morphine + alcohol antagonist treatment after 30 minutes of yawing behavior is recorded for 60 minutes. Group 7 social isolation followed by 6 weeks of treatment with antagonist alcohol (naltrexone), 10 mg / kg, after 30 minutes of yawing behavior is recorded for 60 minutes. Group 8 Social isolation after 6 weeks of treatment with antagonist morphine (naloxone) 1 mg / kg of bad breath after 30 minutes of yawing behavior is recorded for 60 minutes. Group 9 social isolation followed by 6 weeks of treatment with antagonist alcohol + morphine after 30 minutes for 60 minutes of yawing behavior is recorded for 60 minutes. Group 10 social isolation followed by 6 weeks of treatment with antagonist alcohol + morphine antagonist after 30 minutes for 60 minutes of yawing behavior is recorded for 60 minutes. Group 11 Social isolation after 6 treatments with antagonist morphine + alcohol followed after 30 minutes for 60 minutes of yawing behavior is recorded for 60 minutes.&#x0D; Injection of alcohol chronically reduces yawning, but alcohol injections in conditions of social isolation increase the number of yawns. Antagonist injection of naltrexone prior morphine in conditions of social isolation of yawning. Injection of morphine in conditions of social isolation does not change the number of yawning. Injection of morphine antagonist (naloxone) prior to antagonist of alcohol (naltrexone) in conditions of social isolation increases yawn. Also, the injection of morphine antagonist (naloxone) prior to alcohol into social isolation causes an increase in the number of yawns. Alcohol injection before morphine in conditions of social isolation increases the number of yawns.&#x0D; It seems that the stress of social isolation by decreasing alcohol and morphine function increases the number of yawns.

Environmental enrichment mitigates PTSD-like behaviors in adult male rats exposed to early life stress by regulating histone acetylation in the hippocampus and amygdala

Early life stress (ELS) can cause long-term changes in gene expression, affect cognition, mood, and behavior, and increase susceptibility to post-traumatic stress disorder (PTSD) in adulthood, in which the histone acetylation plays a crucial role. Studies have found that environmental enrichment (EE) mitigated the unfavorable outcomes of ELS. However, the underlying mechanism of the histone acetylation is not yet completely clear. The purpose of this study was to explore the effect of EE on the histone acetylation after ELS. In this study, using single prolonged stress (SPS) paradigm in early adolescent rats explored the long-term effects of ELS on behavior, the activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), as well as the acetylation levels of the lysine 9 site of histone H3 (H3K9) and lysine 12 site of histone H4 (H4K12) in the hippocampus and amygdala. Meanwhile, the protective effects of EE intervention were examined. We found that adult male rats exposed to ELS showed behavioral changes, including reduced locomotor activity, increased anxiety-like behaviors, impaired spatial learning and memory, enhanced contextual and cued fear memory, and the HATs/HDACs ratio and acetyl H3K9 (Ac–H3K9) and acetyl H4K12 (Ac–H4K12) were increased in the hippocampus and decreased in the amygdala. Furthermore, EE attenuated the behavioral abnormalities from ELS, possibly through down-regulating the activity of HATs in the hippocampus and up-regulating HDACs activities in the amygdala. These finding suggested that EE could ameliorate ELS-induced PTSD-like behaviors by regulating histone acetylation in the hippocampus and amygdala, reducing the susceptibility to PTSD in adulthood.

Effects on a hypercaloric diet ingested from weaning on sexual behavior of adult male rats

Obesity is a nutritional disorder which has spread across the world mostly due to a more sedentary life style together with an increase in dietary fat and carbohydrate. The scientific literature in the field of obesity shows an extensive amount of clinical and experimental studies dealing with etiopathogeny, intervening problems, prevention and potential intervention. Among them, many studies have examined the impact of obesity in the reproductive field, mainly in the female sphere. The aim of the present study was to investigate whether a hypercaloric diet ingested from weaning interferes with the sexual behavior of adult male rats. Male Wistar rats (at 100 days of age) from the hypercaloric diet group (HD group, n=9) received a hypercaloric diet, containing 4,79 kcal/g and Control animals (n=7) were fed a normocaloric laboratory chow containing 3.78 Kcal/g. For analysis of sexual behavior, one adult male was placed in the observation cage 4 hours after the beginning of the dark phase and 10 min before (for adaptation to the environment) an adult receptive female in natural estrus was introduced. The parameters of sexual behavior (latency and quantity of mounts, intromission and ejaculation), were tape-recorded and registered simultaneously by two investigators, during a 30-min session, with light provided by a 40-watt red lamp. Concerning sexual behavior, the HD animals presented (i) a 70% increase in the amount of incomplete mounts (mounts without intromission), (ii) a 3-fold increase in the latency for the first intromission, (iii) a 27% decrease in the latency for the first pos-ejaculatory intromission, and (iv) a 26% decrease in the frequency of ejaculation. The lower reproductive performance and the tendency of fertility decrease in animals fed a hypercaloric diet from weaning to adulthood, allows us to suggest a negative interference between the ingestion of a hypercaloric diet and these reproductive parameters. Although results obtained from animals should not be directly extrapolated to humans, they may add evidence concerning the deleterious effects of a hypercaloric diet on humans and the species.

Effects of neonatal NMDA-subtype glutamate receptor blockade on behavior of adult male rats

Introduction. Cognitive impairments are important components of the clinical picture of many neuropsychiatric disorders, and are in dire need of evidence-based pharmacotherapeutic approaches.The objective was to test a model of delayed cognitive impairments due to neonatal administration of NMDA receptor antagonists (7th, 9 th, and 11 th days of life).Methods and materials. Male Wistar rats were administered with phencyclidine, 10 mg/kg (Experiment 1), or (+)MK-801, 1 mg/kg (Experiment 2); then «2-choice serial reaction time task», or «reinforcement learning task based on response patterning under interval schedules of reinforcement» in the same adult rats were performed.Results. Experiment 1: rats after neonatal NMDA-blockade performed operant tasks more accurately and made fewer missed attempts as compared to control. Experiment 2: switching to another schedule of reinforcement increased the pause after reinforced responses in both groups; in the experimental group, the duration of the post-reinforcement pause was shorter.Conclusion. Neonatal NMDA receptor blockade affects inhibitory control and attention to sensory stimuli, which manifests, respectively, as increased impulsivity and hyperfocusing in limited-choice conditions.

Chronic rapid eye movement sleep restriction during juvenility has long-term effects on anxiety-like behaviour and neurotransmission of male Wistar rats

Modernity imposes a toll on the sleep time of young population, with concomitant increase in symptoms of anxiety and depression. Whether there is a causal relationship between these events are only now being experimentally tested in humans and rodents. In a previous study, we showed that chronic sleep deprivation in juvenile-adolescent male rats led to increased anxiety-like behaviour and changes in noradrenaline and serotonin in the amygdala and hippocampus. In the present study we investigated whether early chronic sleep restriction affects emotional behaviour, stress response and neurochemistry in adulthood. From 21 to 42 days of age, Wistar male rats were submitted to sleep restriction by the multiple platform method or allowed to sleep freely. Forty-five days after this period, rats were tested in the elevated plus maze (EPM) and blood samples were collected from non-tested rats or 30 and 60 min after the EPM for determination of plasma corticosterone levels. Levels of monoamines were determined in the frontal cortex, hippocampus, amygdala and hypothalamus 60 min after the EPM. Sleep restriction resulted in increased anxiety-like behaviour, decreased noradrenaline levels in the amygdala and dopamine levels in the ventral hippocampus. Anxiety index was positively correlated with increased serotonin metabolism in the frontal cortex and greater dopamine metabolism in the ventral hippocampus, and negatively correlated with dopamine levels in the ventral hippocampus. These results suggest that sleep restriction in juvenility and adolescence induces persistent changes in emotional behaviour in adult male rats and that levels of anxiety are correlated with increased serotonin and dopamine metabolism in specific brain areas.

P.0712 Exercise mitigates the negative effects of a cafeteria diet on antidepressant-like behaviour in adult male rats

P.0712 Exercise mitigates the negative effects of a cafeteria diet on antidepressant-like behaviour in adult male rats

Maternal deprivation induces cytoskeletal alterations and depressive-like behavior in adult male rats by regulating the AKT/GSK3β/CRMP2 signaling pathway

Early-life adverse events exert persistent effects on brain functions and may increase the risk of psychopathology in adulthood. However, the underlying mechanism remains unclear. The purpose of our study was to study the long-lasting effects of maternal deprivation (MD) on depression-related behaviors and microtubule dynamics, and to illuminate the underlying molecular mechanism. Rat pups were separated from the dams for 360 min (MD) or 15 min (brief maternal separation) each day from postnatal day 4 through 10. Rats with MD experience showed significant depressive-like behaviors in adulthood, while brief maternal separation did not alter the behaviors. Behavioral alterations in the MD group were accompanied by alterations in the AKT/GSK3β/CRMP2 signaling pathway and hyperphosphorylation of CRMP2. CRMP2 interacted and colocalized with the cytoskeleton in the hippocampus, and the overlap of CRMP2 and tubulin staining in the hippocampus of MD rats was decreased. In MD rats, the expression of the α-tubulin isoforms Acet-tubulin and Tyr-tubulin changed, and the ratio of Tyr/Acet-tubulin, which is an important marker of microtubule dynamics, was decreased, indicating decreased microtubule dynamics. Furthermore, regulation of the AKT/GSK3β/CRMP2 signaling pathway by an LY294002 microinjection in the hippocampus resulted in cytoskeletal alterations and depressive-like behaviors in rats. These findings suggest that early-life MD induces depressive-like behaviors and cytoskeletal alterations in adult male rats and that the effects may be partly mediated by the AKT/GSK3β/CRMP2 signaling pathway. An understanding of the mechanism underlying the effect of MD on behaviors is crucial for developing pharmacological and psychological interventions for childhood neglect.

Quality of early-life maternal care predicts empathy-like behavior in adult male rats: Linking empathy to BDNF gene expression in associated brain regions

Empathy is the ability to experience a shared affective state as others. It enhances group living and manifests itself as helping behavior towards a distressed person. It also can flourish by nurturing. Recent findings suggest that rodents exhibit empathy-like behavior towards their conspecifics. However, the role of early-life experiences (e.g., maternal care) is not clear on the development of empathy-like behavior. Moreover, brain-derived neutrophilic factor (BDNF) is a pivotal protein in modulating the brain's function and behaviors. Evidence suggests that the expression of the BDNF gene can be affected by the quality of maternal care. In this study, we questioned whether variation in maternal care modulates empathy-like behavior of male rats in adulthood. Additionally, gene expression of BDNF was measured in the amygdala, hippocampus, insula, anterior cingulate cortex, prefrontal cortex, and striatum in these adult male rats. Based on the pattern of maternal care, the offspring were divided into high maternal care (HMC) and low maternal care (LMC) groups. We confirmed that the early-life experience of HMC significantly promoted the empathy-like behavior of rats in adulthood compared to LMC. In terms of gene expression, the HMC group consistently had higher BDNF gene expression in all studied regions, except anterior cingulate cortex which groups were not different. Taken together, it suggests that maternal care in infancy predicts empathy-like behavior in adulthood and differences in BDNF gene expression in different brain regions may reflect the underlying mechanism.

Neonatal Proinflammatory Stress and Expression of Neuroinflammation-Associated Genes in the Rat Hippocampus.

Differential effect of the neonatal proinflammatory stress (NPS) on the development of neuroinflammation in the hippocampus and induction of the depressive-like behavior in juvenile and adult male and female rats was studied. NPS induction by bacterial lipopolysaccharide in the neonatal period upregulated expression of the Il6 and Tnf mRNAs accompanied by the development of depressive-like behavior in the adult male rats. NPS increased expression of the mRNAs for fractalkine and its receptor in the ventral hippocampus of the juvenile male rats, but did not affect expression of mRNAs for the proinflammatory cytokines and soluble form of fractalkine. NPS downregulated expression of fractalkine mRNA in the dorsal hippocampus of juvenile males. No significant effects of NPS were found in the female rats. Therefore, the NPS induces long-term changes in the expression of neuroinflammation-associated genes in different regions of the hippocampus, which ultimately leads to the induction of neuroinflammation and development of depressive-like behavior in male rats.

Perinatal Stress and Methamphetamine Exposure Decreases Anxiety-Like Behavior in Adult Male Rats.

Methamphetamine (MA) is an illicit synthetic psychostimulant drug, and its abuse is growing worldwide. MA has been reported as the primary drug of choice, by drug-abusing women, during pregnancy. Since MA easily crosses the placental barrier, the fetus is exposed to MA in a similar fashion to the mother. This study aimed to evaluate the effect of long-term perinatal stressors and drug exposure on anxiety-like behavior in adult male rats using the open field test (OF) and elevated plus maze (EPM). Dams were divided into three groups according to drug treatment during pregnancy: controls (C), saline—SA [subcutaneous (s.c.), 1 ml/kg], and MA (s.c., 5 mg/kg). Litters were divided into four groups according to postnatal stressors: non-stressed controls (N), maternal separation (S), maternal cold water stress (W), and maternal separation plus maternal cold water stress (SW). Forty-five minutes before testing (in both OF and EPM), one-half of adult male rats received an (s.c.) injection of MA and the other half received an SA injection. Prenatal MA/stress exposure did not affect anxiety-like behavior in adult male rats in both tests. In the OF, an acute MA dose in adulthood increased the time spent in the central disk area, decreased time spent in the corners, and decreased time spent immobile and grooming. Also, postnatal stress increased time spent in the central disk area, decreased time spent in corners, and increased mobility compared to controls. All groups of rats exposed to postnatal stressors spent significantly less time in the closed arms of the EPM compared to controls. Overall, our results indicate that early postnatal stress and a single acute MA administration in adulthood decreases the parameters of anxiety-like behavior in adult male rats regardless of prenatal MA exposure. Moreover, postnatal stress via maternal separation impacts the effect of acute MA administration in adulthood. Long-term postnatal stress may thus result in improved adaptation to subsequent stressful experiences later in life.

Long-Term Decreases in the Expression of Calcineurin and GABAA Receptors Induced by Early Maternal Separation Are Associated with Increased Anxiety-Like Behavior in Adult Male Rats

Introduction: Early life stress is a well-described risk factor of anxiety disorders in adulthood. Dysfunction in GABA/glutamate receptors and their functional regulator, calcineurin, is linked to anxiety disorders. Here, we investigated the effect of early life stress, such as repeated maternal separation (MS; 3 h per day from postnatal day [P] 2 to 11), on changes in the expression of calcineurin as well as the ionotropic glutamatergic and GABAergic receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and GABA_A receptors in the hippocampus and prefrontal cortex (PFC) of adolescent (P35) and adult (P62) male Wistar rats and their correlations with anxiety-like behavior in adulthood. Methods: The protein levels were assessed by Western blot analysis. Anxiety-like behavior was measured in the elevated plus maze (EPM) and open field (OF) tests. Results: MS induced a regional transient decrease of glutamate receptors expression at P35, with decreased NMDA and AMPA receptor levels, respectively, in the hippocampus and PFC, suggesting a possible decrease in excitatory synaptic strength. In contrast to glutamate receptors, MS had long-lasting influence on GABA_A receptor and calcineurin levels, with reduced expression of GABA_A receptor and calcineurin in both brain regions at P35 that continued into adulthood. These results were accompanied by increased anxiety behavior in adulthood, shown by lower percentage of number of total entries and time spent in the open arms of the EPM, and by lower time spent and number of entries in the OF central area. Conclusions: Together, our study suggests that GABA_A receptors via calcineurin-dependent signaling pathways may play an important role in the expression of stress-induced anxiety-like behavior.

Vitamin C protects against chronic social isolation stress-induced weight gain and depressive-like behavior in adult male rats.

Objective. Considering the importance of ghrelin in stress-induced hyperphagia and a role of antioxidants in decreasing body weight, in the present study, the effect of vitamin C (VitC) on ghrelin secretion and food intake following chronic social isolation (CIS) was evaluated in rats.Methods. Thirty two male Wistar rats (200-220g) were randomly divided into: control, VitC, CIS, and CIS + VitC groups. Animals received VitC (500 mg/kg/day)/saline by gavage for 3 weeks. For 24 h cumulative and post 18-20 h fasting food intake, fasting plasma ghrelin level, and body weight were measured. Gastric histopathology was also evaluated.Results. Results showed a marked increase in fasting plasma ghrelin and food intake in stressed rats compared to controls. VitC prevented the increases in stressed rats. Histological assessment indicated a positive effect of VitC on gastric glandular cells compared to control, an effect that might partially be a reason of significant increase of plasma ghrelin levels in VitC rats. Elevated plasma ghrelin in VitC group was even higher than that one in stressed group, whereas there were no significant changes in the food intake. Assessment of the percentage of changes in body weight during 21 days showed a significant increase in stressed rats compared to controls. Vitamin C treatment prevented this increase. Stressed rats also displayed depression-like behavior as indicated by sucrose test, whereas VitC ameliorated it.Conclusions. The data of the present study indicate that VitC may overcome ghrelin-induced hyperphagia and improve the abnormal feeding and depressive behavior in CIS rats.

Chronic Maternal Tobacco Smoke Exposure and/or Alpha-Lipoic Acid Treatment Causes Long-Term Deterioration of Testis and Sexual Behavior in Adult Male Rats

BackgroundTobacco use during pregnancy is known to have several negative effects on the offspring's reproductive health in the long term. The use of alpha-lipoic acid (ALA) as a dietary supplement during pregnancy has increased greatly in recent years and has been known to have positive effects on various pregnancy outcomes including miscarriage, diabetic embryopathy, preterm delivery, and congenital malformations. AimTo evaluate the effects of tobacco smoke exposure (TSE) on sexual behavior, reproductive parameters, and testicles in adult male rats and to reveal the possible role of ALA administration on these parameters. MethodsPregnant rats (n = 7 per group) were treated with tobacco smoke (TS), ALA (20 mg/kg), and TS + ALA for a total of 11 weeks. The following parameters were compared with 8 control rats: puberty parameters, sexual behavior; levels of serum gonadotropins and testosterone, total antioxidant status, and total oxidant status; the expression of the apoptotic protease-activating factor-1 and caspase 9 mRNA levels in the testis; and assessment of immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay of testis. Main Outcome MeasureSexual behavior, changes in puberty parameters, and hormonal and genetic alterations were the outcomes analyzed in this study. ResultsMaternal TSE caused a significant decrease in the number of intromissions compared to the control group. Similarly, ALA decreased erectile function in sexual behavior by decreasing the number of intromissions and intromission ratio in the ALA group compared to the control group. In addition, TSE and ALA treatment caused an impairment of some consummatory sexual behaviors. Also, in parallel with this inhibitory effect, the age of pubertal onset was significantly delayed in the TS + ALA group compared to other groups. Also, histopathological changes in testicular tissue, oxidative stress markers, apoptotic index, and mRNA levels of apoptosis-related genes increased in all treatment groups. Clinical ImplicationsThe use of ALA and/or tobacco products during pregnancy may adversely affect the reproductive health of male newborns in the long term. Strengths & LimitationsTo the best of our knowledge, this study is the first to show the effects of maternal ALA treatment and/or TSE on the sexual behavior and reproductive parameters in male rats; however, the study is based on an animal model, and the present findings partially reflect the characteristics of human sexual behavior. ConclusionMaternal TSE and/or ALA treatment may impair sexual behavior in adulthood in male rats because of testicular damage caused by oxidative stress during gonadal development.Yardimci A, Akkoc RF, Tektemur A, et al. Chronic Maternal Tobacco Smoke Exposure and/or Alpha-Lipoic Acid Treatment Causes Long-Term Deterioration of Testis and Sexual Behavior in Adult Male Rats. J Sex Med 2020;17:1835–1847.

Antagonizing serotonin 2A (5-HT2A) receptors attenuates methamphetamine-induced reward and blocks methamphetamine-induced anxiety-like behaviors in adult male rats

BackgroundMethamphetamine is a highly addictive and abused psychostimulant. Symptoms of methamphetamine withdrawal including drug craving and anxiety that can drive relapse. Currently, there is no FDA approved treatment for methamphetamine use disorder, highlighting the need for research examining the neural mechanisms underlying psychostimulant-induced behaviors. Research indicates that the 5-HT2A receptor antagonist M100907 attenuates several psychostimulant-induced behaviors, including conditioned place preference (CPP). However, these findings have not been extended to methamphetamine. The present study investigated the effects of M100907 on acquisition of methamphetamine-CPP and methamphetamine-induced anxiety-like behavior. MethodsAdult male rats were tested across eight consecutive days. Prior to methamphetamine administration (0 or 1 mg/kg, i.p.), rats were pretreated with their assigned dose of M100907 (0, 0.0025 .025 or 0.25 mg/kg, i.p.) and were placed into their initially non-preferred chamber. After four methamphetamine conditioning sessions, the effects of M100907 on methamphetamine-induced CPP were assessed. Following CPP testing, rats were screened for anxiety-like behaviors in the elevated plus-maze. ResultsPretreatment with M100907 attenuated methamphetamine-induced CPP without producing any observable rewarding or aversive effects in methamphetamine naïve rats. Additionally, M100907 blocked methamphetamine-induced increases in anxiety-like behavior and attenuated some indices of anxiety in methamphetamine naïve rats. ConclusionsResults suggest that blocking 5-HT2A receptors with the selective antagonist M100907 attenuates the rewarding effects of methamphetamine and does not produce any rewarding or aversive effects alone. Further, M100907 pretreatment blocked the anxiety-inducing effects of methamphetamine. Collectively, these data suggest that the 5-HT2A receptor subtype represents a novel target for treating methamphetamine use disorder.