Onset Of Behavioral Changes Research Articles

The beneficial effect of fluoxetine on behavioral and cognitive changes in chronic experimental Chagas disease unveils the role of serotonin fueling astrocyte infection by Trypanosoma cruzi.

In Chagas disease (CD), a neglected tropical disease caused by the parasite Trypanosoma cruzi, the development of mental disorders such as anxiety, depression, and memory loss may be underpinned by social, psychological, and biological stressors. Here, we investigated biological factors underlying behavioral changes in a preclinical model of CD. In T. cruzi-infected C57BL/6 mice, a kinetic study (5 to 150 days postinfection, dpi) using standardized methods revealed a sequential onset of behavioral changes: reduced innate compulsive behavior, followed by anxiety and depressive-like behavior, ending with progressive memory impairments. Hence, T. cruzi-infected mice were treated (120 to 150 dpi) with 10 mg/Kg/day of the selective serotonin reuptake inhibitor fluoxetine (Fx), an antidepressant that favors neuroplasticity. Fx therapy reversed the innate compulsive behavior loss, anxiety, and depressive-like behavior while preventing or reversing memory deficits. Biochemical, histological, and parasitological analyses of the brain tissue showed increased levels of the neurotransmitters GABA/glutamate and lipid peroxidation products and decreased expression of brain-derived neurotrophic factor in the absence of neuroinflammation at 150 dpi. Fx therapy ameliorated the neurochemical changes and reduced parasite load in the brain tissue. Next, using the human U-87 MG astroglioma cell line, we found no direct effect of Fx on parasite load. Crucially, serotonin/5-HT (Ser/5-HT) promoted parasite uptake, an effect increased by prior stimulation with IFNγ and TNF but abrogated by Fx. Also, Fx blocked the cytokine-driven Ser/5-HT-promoted increase of nitric oxide and glutamate levels in infected cells. We bring the first evidence of a sequential onset of behavioral changes in T. cruzi-infected mice. Fx therapy improves behavioral and biological changes and parasite control in the brain tissue. Moreover, in the central nervous system, cytokine-driven Ser/5-HT consumption may favor parasite persistence, disrupting neurotransmitter balance and promoting a neurotoxic environment likely contributing to behavioral and cognitive disorders.

Ethical considerations in the treatment of chronic psychosis in a periviable pregnancy

Background: Treatment of psychotic disorders in pregnancy is often ethically and clinically challenging, especially when psychotic symptoms impair decision-making capacity. There are several competing ethical obligations to consider: the ethical obligation to maternal autonomy, the maternal and fetal beneficence-based obligations to treat peripartum psychosis, and the fetal beneficence-based obligation to minimize teratogenic exposure. Objective: This article outlines an ethical framework for clinical decision-making for the management of chronic psychosis in pregnancy, with an emphasis on special considerations in the previable and periviable period. Case Presentation: A 31-year-old gravida 2, para 1 with intrauterine pregnancy at 12 weeks and 4 days gestation was brought to the emergency department by her husband seven months after delivering her first child, due to sudden onset of behavioral changes that included self-isolation, not eating, and not taking care of her child. Her past medical history included hypothyroidism and inflammatory bowel disease, but no prior psychiatric illness. After being admitted to the psychiatric hospital, she continued to have poor oral intake and weight loss despite initial inpatient treatment with antipsychotics, levothyroxine, and discontinuation of corticosteroids. Her pregnancy was also complicated by the diagnosis of multiple fetal anomalies at 20 weeks gestation, when the fetus was periviable. Conclusions: For previable or periviable pregnancies, the patient and/or surrogate should decide whether to pursue prenatal genetic screening and invasive diagnostic testing, as well as whether to continue or terminate the pregnancy. When the choice is made to continue the pregnancy, initiation of long-term psychiatric treatment (including medications with potential adverse fetal effects) should be based on shared decision-making between the physician and the patient and/or surrogate. Although some pharmacologic interventions may have potential adverse effects on the developing fetus, the use of psychotropic medications can be ethically justified, even if the patient herself does not have the capacity to consent and requires a surrogate, when the goal is to restore maternal autonomy and minimize the risks of maternal and fetal harm from untreated psychiatric illness.

A Young Child with Subacute Onset of Behavioral Changes.

1. Sarah Pradhan, MD* 2. Jessica Goldstein, MD† 3. Erin Frank, MD* 4. Allayne Stephans, MD* 1. *Department of Pediatric Hospital Medicine, 2. †Department of Pediatric Neurology, Rainbow Babies and Children’s Hospital, Cleveland, OH 1. Address Correspondence to Sarah Pradhan, MD; E-mail: sarah.pradhan6{at}gmail.com A 5-year-old healthy boy presents with a 3-week history of new onset aggression, obsessive-compulsive behavior, and nocturnal enuresis. One month ago he sustained a minor head trauma when he was sliding down the slide at a local playground. He was initially diagnosed with a mild concussion. His symptoms have now progressed and include frequent night waking, hand wringing, and behavioral outbursts. This prompts his pediatrician to refer him to the emergency department for evaluation. He undergoes computed tomography scan of the head, which is unremarkable. Laboratory evaluations include electrolytes, liver enzymes, complete blood cell count, rapid group A streptococcal antigen, thyroids studies, and heterophile antibody test, which are unremarkable. Urine and blood toxicology screens are negative. He is admitted to the inpatient unit. Vital signs are appropriate for age. He has difficulty answering questions and following commands. He is restless and disoriented. He intermittently gets up to run around the room and occasionally bangs his head on the wall. His cranial nerve, motor, reflexes, sensory, coordination, and gait examinations are normal. Brain magnetic resonance imaging is unremarkable. On video electroencephalogram he has bilateral fronto-temporal spikes that correspond with his abnormal movements and subclinical seizures arising from the right and left frontotemporal areas independently (arrows in Fig 1). Fosphenytoin is started, which controls his seizures, but he continues to have abnormal behavioral outbursts. Over the course of the week, he develops dysarthria, oral-facial …

A case report of complement C4B deficiency in a patient with steroid and IVIG-refractory anti-NMDA receptor encephalitis

BackgroundComplement C4A or C4B deficiency has never been reported in autoantibody-associated encephalitides patient. Here we present a case of anti-N-methyl- D-aspartate (NMDA) receptor encephalitis associated with homozygous C4B deficiency, who did not respond to intravenous immunoglobulin and pulse methylprednisolone but plasmapheresis and rituximab.Case presentationA fourteen-year-old boy presented to our unit with subacute onset of behavioral changes and confusion, and was later confirmed to be anti-NMDA receptor encephalitis. He was initially managed with intravenous immunoglobulin (IVIG) and pulse methylprednisolone but did not achieve any clinical improvement. Seven sessions of plasmapheresis was commenced with remarkable improvement after the second session, and was followed by four doses of rituximab. His neurological and cognitive functioning gradually returned to baseline. Immunological investigations demonstrated persistently low C4 levels below 8 mg/dL. A more in-depth complement analysis of the patient and his family showed that he has homozygous C4B deficiency. Genetic analysis revealed that the index patient has homozygous deficiency in complement C4B and he carries one non-functioning mutant C4B gene inherited from his mother.ConclusionsLow levels of serum C4 correlate with reduced functions of the classical and lectin pathways, leading to the impairment of immune-complexes removal. Plasmapheresis ameliorates complement deficiency and removes the offending immune-complexes leading to clinical improvement that was not achieved by IVIG and steroids. We postulate that serum C4 levels may serve as a biomarker for the need of plasmapheresis upfront rather than only after non-response to steroid and IVIG in treating anti-NMDA-receptor encephalitis.

Herpes simplex virus limbic encephalitis in a Filipino man with advanced stage testicular cancer: A case report

A 66-year-old Filipino Male, Hypertensive, Diabetic, diagnosed with Advanced Testicular Cancer presented with a five day history of fever, productive cough associated with sudden onset of behavioral changes, memory lapses and disorientation. On admission, the patient was disoriented, with poor comprehension and inability to follow commands. There were no focal motor deficits or signs of meningeal irritation. Cranial CT scan and serum electrolytes were unremarkable. CBC showed leukocytosis with predominant neutrophils, chest xray revealed pneumonia. Piperacillin+ Tazobactam and Azithromycin was started On the second hospital day, he had seizures manifested as blank stares, teeth grinding, lip smacking and fidgety movement of the right hand. Electroencephalogram showed epileptiform discharges in both frontal-prefrontal and both frontal-central regions. A cranial MRI with Contrast revealed high T2W and FLAIR signal changes and edema in the mesial temporal lobes and right insula (Figure 1) and right lentiform nucleus (Figure 2). EEG and MRI findings are consistent with Limbic Encephalitis based on the diagnostic criteria by Gultekin et al.1(2014). A lumbar puncture yielded a colorless cerebrospinal fluid (CSF) with normal opening pressure, normal RBC and WBC, lymphocytic predominance (96%), elevated CSF protein and normal CSF glucose. CSF Acid Fast Bacilli (AFB), KOH and India Ink were all negative. Further CSF analysis for neuronal autoantibodies specifically Anti-NMDA, Anti- Hu and Anti- Ma2 were likewise negative. Polymerase Chain Reaction (PCR) assay for Herpes Simplex Virus was positive for HSV-1. Intravenous Acyclovir was started at 15mg/kg per day. After three weeks of antiviral therapy the patient's condition improved.

Levetiracetam induced behavioral changes: a case report

A 16-year-old girl with a long-standing history of epilepsy and mild learning disability, presented to the neurology unit of the National Hospital of Sri Lanka with a history of abrupt onset of behavioral changes after the initiation of levetiracetam therapy. She did not have any psychiatric illness or behavioural changes prior to this episode, and her symptoms were not related to any seizure episodes. Her symptoms gradually declined within a week of the cessation of levetiracetam.

Neurodevelopmental Changes in Excitatory Synaptic Structure and Function in the Cerebral Cortex of Sanfilippo Syndrome IIIA Mice

Sanfilippo syndrome, MPS IIIA-D, results from deficits in lysosomal enzymes that specifically degrade heparan sulfate, a sulfated glycosaminoglycan. The accumulation of heparan sulfate results in neurological symptoms, culminating in extensive neurodegeneration and early death. To study the impact of storage in postnatal neurodevelopment, we examined murine models of MPS IIIA, which lack the enzyme sulfamidase. We show that changes occur in excitatory postsynaptic structure and function in the somatosensory cortex prior to signs of neurodegeneration. These changes coincide with accumulation of heparan sulfate with characteristic non-reducing ends, which is present at birth in the mutant mice. Accumulation of heparan sulfate was also detected in primary cultures of cortical neural cells, especially astrocytes. Accumulation of heparan sulfate in cultured astrocytes corresponded with augmented extracellular heparan sulfate and glypican 4 levels. Heparan sulfate from the cerebral cortex of MPS IIIA mice showed enhanced ability to increase glutamate AMPA receptor subunits at the cell surface of wild type neurons. These data support the idea that abnormalities in heparan sulfate content and distribution contribute to alterations in postsynaptic function. Our findings identify a disease-induced developmental phenotype that temporally overlaps with the onset of behavioral changes in a mouse model of MPS IIIA.

Short communication: Rumination and feeding behaviors differ between healthy and sick dairy cows during the transition period.

The objectives of this study were: (1) to describe the rumination and feeding behavior of freestall-housed Holstein dairy cows in the weeks around parturition, and (2) to determine the relationship between postpartum disease and precalving rumination and feeding behavior. Eighty cows were enrolled at approximately 2wk (18±7d, mean ± standard deviation) before calving. Using automatic monitoring systems, rumination and feeding behavior were recorded continuously from 10d before until 3wk after calving. Postpartum health checks were performed each day, and metritis assessment was conducted 2 times/wk. Blood β-hydroxybutyrate was measured 3 times/week, and cows with ≥1.2mmol/L during the first 14d postpartum were diagnosed as having subclinical ketosis. The final data set included 64 cows in 5 groups: healthy (n=20), metritis (n=18), subclinical ketosis (SCK; n=9), metritis+SCK (n=9), and >1 health problem and not included before (MULT, n=8). We compared rumination and feeding data between healthy cows and the 4 categories of ill animals in each of 4 periods relative to calving: precalving (d -7 to -2), period 1 (d 3 to 8 postpartum), period 2 (d 9 to 14 postpartum), and period 3 (d 15 to 20 postpartum). Cows with SCK spent less time ruminating during the precalving period. Compared with healthy cows, those with SCK and metritis+SCK had lower dry matter intake during the precalving period and continued to eat less until d 14 and d 20 postpartum, respectively. Cows with metritis and MULT cows had lower dry matter intake during the first 2wk postpartum. Precalving feeding time was lower for SCK, metritis+SCK, and MULT cows compared with healthy cows. The difference in feeding time between healthy and metritis+SCK cows had disappeared by period 2 and between all health categories except MULT by period 3. MULT cows visited the feed bins less often and were less often replaced at the feed bin throughout all 4 periods of the study. Automatic monitoring of intake and rumination showed promise for the detection of health problems after calving. We observed differences in precalving rumination and feeding behavior. Further research is necessary to better understand the onset of behavioral changes and the relationship between rumination and disease.

Baclofen Toxicity Causing Acute, Reversible Dyskinesia

The following unique case demonstrates an episode of acute dyskinesia secondary to oral baclofen toxicity. We discuss an 80-year-old man with a history of Stage III chronic kidney disease, coronary artery disease, diabetes and stroke who presented to the Emergency Department with new onset of behavioral changes and irregular jerking movements. The patient had been recently prescribed baclofen 10mg twice daily for a back strain he suffered; he subsequently was admitted to the hospital, and his symptoms resolved within 48 hours of admission and discontinuance of baclofen.

Identifying the Basal Ganglia network model markers for medication-induced impulsivity in Parkinson's disease patients.

Impulsivity, i.e. irresistibility in the execution of actions, may be prominent in Parkinson's disease (PD) patients who are treated with dopamine precursors or dopamine receptor agonists. In this study, we combine clinical investigations with computational modeling to explore whether impulsivity in PD patients on medication may arise as a result of abnormalities in risk, reward and punishment learning. In order to empirically assess learning outcomes involving risk, reward and punishment, four subject groups were examined: healthy controls, ON medication PD patients with impulse control disorder (PD-ON ICD) or without ICD (PD-ON non-ICD), and OFF medication PD patients (PD-OFF). A neural network model of the Basal Ganglia (BG) that has the capacity to predict the dysfunction of both the dopaminergic (DA) and the serotonergic (5HT) neuromodulator systems was developed and used to facilitate the interpretation of experimental results. In the model, the BG action selection dynamics were mimicked using a utility function based decision making framework, with DA controlling reward prediction and 5HT controlling punishment and risk predictions. The striatal model included three pools of Medium Spiny Neurons (MSNs), with D1 receptor (R) alone, D2R alone and co-expressing D1R-D2R. Empirical studies showed that reward optimality was increased in PD-ON ICD patients while punishment optimality was increased in PD-OFF patients. Empirical studies also revealed that PD-ON ICD subjects had lower reaction times (RT) compared to that of the PD-ON non-ICD patients. Computational modeling suggested that PD-OFF patients have higher punishment sensitivity, while healthy controls showed comparatively higher risk sensitivity. A significant decrease in sensitivity to punishment and risk was crucial for explaining behavioral changes observed in PD-ON ICD patients. Our results highlight the power of computational modelling for identifying neuronal circuitry implicated in learning, and its impairment in PD. The results presented here not only show that computational modelling can be used as a valuable tool for understanding and interpreting clinical data, but they also show that computational modeling has the potential to become an invaluable tool to predict the onset of behavioral changes during disease progression.

Environmental Enrichment Duration Differentially Affects Behavior and Neuroplasticity in Adult Mice.

Environmental enrichment is a powerful way to stimulate brain and behavioral plasticity. However the required exposure duration to reach such changes has not been substantially analyzed. We aimed to assess the time-course of appearance of the beneficial effects of enriched environment. Thus, different behavioral tests and neurobiological parameters (such as neurogenesis, brain monoamines levels, and stress-related hormones) were concomitantly realized after different durations of enriched environment (24 h, 1, 3, or 5 weeks). While short enrichment exposure (24 h) was sufficient to improve object recognition memory performances, a 3-week exposure was required to improve aversive stimulus-based memory performances and to reduce anxiety-like behavior; effects that were not observed with longer duration. The onset of behavioral changes after a 3-week exposure might be supported by higher serotonin levels in the frontal cortex, but seems independent of neurogenesis phenomenon. Additionally, the benefit of 3-week exposure on memory was not observed 3 weeks after cessation of enrichment. Thus, the 3-week exposure appears as an optimal duration in order to induce the most significant behavioral effects and to assess the underlying mechanisms. Altogether, these results suggest that the duration of exposure is a keystone of the beneficial behavioral and neurobiological effects of environmental enrichment.

Focal nonconvulsive seizures during detoxification for benzodiazepine abuse

Chronic benzodiazepine (BDZ) abuse is currently treated with detoxification using a low-dose flumazenil infusion, a relatively recently developed and promising procedure. Given the possibility reported in the literature of the occurrence of generalized seizures during therapeutic BDZ detoxification, we usually administer preventive antiepileptic drug (AED) therapy. We describe two patients with no previous history of seizures or evidence of intracerebral lesions who, during detoxification for benzodiazepine abuse, developed repetitive focal nonconvulsive seizures instead of generalized seizures, even with appropriate doses of preventive AED therapy. There are no previous reported cases of focal nonconvulsive seizures occurring during this procedure or, more generally, during abrupt BDZ discontinuation. The cases we describe suggest that during detoxification for BDZ abuse, not only generalized, but also focal nonconvulsive seizures may occur. In this context, the focal seizures probably result from a diffuse decrease in the seizure threshold (caused by a generalized excitatory rebound), which may trigger focal seizures arising from cortical regions with higher intrinsic epileptogenicity. Detoxification for benzodiazepine abuse, even if performed with adequate-dosage AED treatment, may not be as safe a procedure as previously considered, because not only convulsive, but also nonconvulsive seizures may occur and go unnoticed. It is therefore strongly advisable to perform this detoxification under close medical supervision and to maintain a low threshold for EEG monitoring in the event of sudden onset of behavioral changes.

Neurobehavioral Features in Frontotemporal Dementia With Amyotrophic Lateral Sclerosis

To compare the clinical features at presentation in patients with frontotemporal dementia (FTD) who develop amyotrophic lateral sclerosis (ALS) with those of patients with behavioral variant FTD (bvFTD) who do not develop ALS. Archival data analysis on 61 deceased patients with FTD. We reviewed the clinical features at presentation (behavioral changes, psychotic symptoms, language, and executive and memory problems) and survival. Early Onset Dementia Clinic, Cambridge, England. Patients From a total of 156 patients with a clinical diagnosis of behavioral FTD, we selected 61 deceased patients with comprehensive medical records, including 43 with bvFTD and 18 with FTD/ALS. Clinical features and survival. There was a significant association between the presence of delusions (50%; odds ratio, 4.4; 95% confidence interval, 1.3-14.5) and diagnosis of FTD/ALS (n = 18), whereas the behavioral features were identical in both groups. The interval between the onset of behavioral changes and diagnosis of ALS was less than 2 years in 12 (67%) of the patients with FTD/ALS. The median survival from symptom onset was significantly shorter for the FTD/ALS group (2.4 years; 95% confidence interval, 1.8-3.0 years) than for the bvFTD group (6.6 years; 5.6-7.6 years). Delusions are particularly common in patients who develop FTD/ALS. The occurrence of delusions in the context of behavioral FTD should lead to an early search for ALS features.

Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice.

Alzheimer's disease (AD) is associated with accumulations of amyloid-beta (Abeta) peptides, oxidative damage, mitochondrial dysfunction, neurodegeneration, and dementia. The mitochondrial antioxidant manganese superoxide dismutase-2 (Sod2) might protect against these alterations. To test this hypothesis, we inactivated one Sod2 allele (Sod2(+/-)) in human amyloid precursor protein (hAPP) transgenic mice, reducing Sod2 activity to approximately 50% of that in Sod2 wild-type (Sod2(+/+)) mice. A reduction in Sod2 activity did not obviously impair mice without hAPP/Abeta expression. In hAPP mice, however, it accelerated the onset of behavioral alterations and of deficits in prepulse inhibition of acoustic startle, a measure of sensorimotor gating. In these mice, it also worsened hAPP/Abeta-dependent depletion of microtubule-associated protein 2, a marker of neuronal dendrites. Sod2 reduction decreased amyloid plaques in the brain parenchyma but promoted the development of cerebrovascular amyloidosis, gliosis, and plaque-independent neuritic dystrophy. Sod2 reduction also increased the DNA binding activity of the transcription factor nuclear factor kappaB. These results suggest that Sod2 protects the aging brain against hAPP/Abeta-induced impairments. Whereas reductions in Sod2 would be expected to trigger or exacerbate neuronal and vascular pathology in AD, increasing Sod2 activity might be of therapeutic benefit.

An integrated, temporal study of the behavioural, electrophysiological and neuropathological consequences of murine prion disease

We have conducted an integrated study of ME7 prion disease by examining the electrophysiological and neuropathological features of hippocampal slices from behaviourally characterised C57Bl/6J mice 12, 14, 16, 18, 20 and 24 weeks after intracerebral micro-injection of ME7 or normal brain homogenate. We describe the pathogenesis of ME7 as a three-stage process. STAGE ONE: PrPSc deposition, synaptic pathology and abnormal synaptic plasticity. STAGE TWO: Onset of behavioural changes, exemplified by an increase in open-field activity, enhancement of the slow AHP and development of vacuolation. Membrane depolarisation is also an early feature, but its exact timing remains to be confirmed. STAGE THREE: Clinical disease, substantial neurodegeneration and further disruption of the action potential profile. We suggest that the mechanisms underlying the electrophysiological changes of Stages one and two may provide novel approaches to treatment of prion disease, and that those seen in Stage three may be relevant to neurodegenerative diseases more generally.

An investigation of potential neurosurgical transmission of Creutzfeldt-Jakob disease: Challenges and lessons learned

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurologic disorder characterized by an insidious onset of behavioral changes, dementia, cerebellar dysfunction, and movement disorders that rapidly progress to death. Iatrogenic transmission has been reported and associated with use of contaminated human growth hormone, dura mater and corneal grafts, depth electrodes, and in only four instances, with neurosurgical equipment. OBJECTIVE: Conduct an epidemiologic investigation surrounding a case of possible CJD transmission associated with neurosurgery. METHODS: Review medical and surgical records of the two CJD patients. Seek additional cases by matching death certificates and the New York State Department of Health dementia registry with list of patients undergoing neurosurgery. RESULTS: A 69-year-old man underwent a brain biopsy to rule out a presumed diagnosis of herpes encephalitis. Histological examination revealed spongiform degeneration of the cerebral cortex consistent with CJD. The following month, a 63-year-old man underwent a steriotactic-guided brain biopsy at the same hospital. Histologic examination revealed subacute necrosis of brain parenchyma with granulomatous vasculitis (no evidence of CJD). Approximately 6.5 years later, the patient was diagnosed with CJD. The only device known to have been used on both patients was a pneumatic drill, but different drill bits were used. The instruments used to open the dura were not described in the operative reports. Due to closure of the hospital, operating room logs, reprocessing records, and staff were not available for review or interview. None of the other subsequent neurosurgical patients is known to have died with a diagnosis of CJD. CONCLUSIONS: Transmission of CJD is extremely difficult, if not impossible, to prove on the basis of a single case. This investigation points out the difficulty of linking CJD patients, evaluating evidence of possible transmission, and preventing transmission. Current prevention and control strategies include screening organ and tissue donors for CJD prior to transplantation, identifying suspected CJD patients prior to high-risk surgery, and ensuring that potentially contaminated surgical instruments undergo the CJD-specific cleaning and sterilization processes recommended by the Centers for Disease Control and Prevention (CDC). Suspected nosocomial or iatrogenic transmission of CJD should be reported to state or local health departments and/or to the CDC.

Necrosis of hippocampus and piriform lobe: clinical and neuropathological findings in two Italian cats

The present paper reports the clinical and neuropathological findings in two cats with a neuropathologically confirmed diagnosis of necrosis of the hippocampus and piriform lobe. The cats were presented because of acute onset of behavioural changes and complex partial seizures. The neurological examination suggested a forebrain lesion. The results of blood examination were within the normal range, and the cerebrospinal fluid (CSF) analysis and computed tomography (CT) scan in one cat did not show any abnormality. Despite therapy with diazepam (Valium ®; Roche) there was deterioration of the clinical signs and the cats were euthanased. The neuropathological examination revealed hippocampal necrosis that included the piriform lobe.

Increased stress vulnerability after a prefrontal cortex lesion in female rats

Neuroimaging studies in patients suffering from affective disorders have shown decreased volume and reduced regional cerebral blood flow in multiple areas of the prefrontal cortex, including the medial prefrontal cortex and the orbitofrontal cortex. This aberrant brain activity is among other things attributed to chronic stress. Affective disorders occur more often in women than in men. In the current experiment, female mPFC-lesioned and non-lesioned rats were subjected to 3 weeks of chronic unpredictable stress in order to determine the role of the mPFC in dealing with chronic stress, and the consequences of mPFC damage for coping with consecutive stressful events. mPFC damage in female rats intensified the stress-induced activation of the dorsomedial nucleus of the hypothalamus and the paraventricular nucleus of the hypothalamus as measured with Fos expression changes and markedly increased plasma catecholamine levels after 3 weeks of unpredictable stress. Additionally, an mPFC lesion significantly reduced the time of appearance of stress-induced behavioral changes in the open field. Altogether, mPFC dysfunction affects the way female rats react to chronic stress, it not only increased the activation of brain regions involved in neuroendocrine and autonomic responses to stress but it also significantly reduced the time of onset of behavioral changes.

Animals Can Model Psychiatric Symptoms

Animals Can Model Psychiatric Symptoms

Modulation of cytokine responses in Corynebacterium parvum-primed endotoxemic mice by centrally administered cannabinoid ligands

The cannabinoid receptor agonists [(−)-11-hydoxy-Δ 8tetrahydrocannabinol-dimethylheptyl] (HU-210) and {( R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl[pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthalenyl) methanone} (WIN 55212-2) were previously shown to downregulate inflammatory cytokines (tumor necrosis factor α and interleukin-12) and to upregulate antiinflammatory interleukin-10 when administered intraperitoneally (i.p.) to mice before an endotoxin challenge. Cytokine modulation coincided with the onset of behavioral changes that are associated with cannabinoid agonist activated central cannabinoid CB 1 receptors. Both effects were antagonized by [ N-(piperdin-1-yl)-5-(4-chloropheny)-1-(2,4-dichloropheny)-4-methyl-1 H-pyrazole-3-carboxamide hydrochloride] (SR141716A) a selective cannabinoid CB 1 receptor antagonist. In the present study, we have investigated further the apparent role of central CB 1 cannabinoid receptors in cytokine modulation by HU-210 and WIN 55212-2. When administered intracerebroventricularly (i.c.v.), the drugs modulated cytokine responses at doses that were threefold to fourfold lower than those found effective by the i.p. route. SR141716A blocked cytokine modulation when coadministered centrally with the agonists, while a selective cannabinoid CB 2 receptor antagonist, { N-[(1 S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]5-(4-choro-3 methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide} (SR144528) had no effect. Surprisingly, SR144528 was found to modulate cytokines itself when injected i.c.v.