Acute Behavioral Changes Research Articles

Agmatine

Agmatine is an endogenous neuromodulator that, based on animal studies, has the potential for new drug development. As an endogenous aminoguanidine compound (1-amino-4-guanidinobutane), it is structurally unique compared with other monoamines. Agmatine was long thought to be synthesised only in lower life forms, until its biosynthetic pathway (decarboxylation of arginine) was described in the mammalian brain in 1994. Human arginine decarboxylase has been cloned and shown to have 48% identity to ornithine decarboxylase. In neurons of the brain and spinal cord, agmatine is packaged into synaptic vesicles and released upon neuronal depolarisation. Other evidence of a neuromodulation role for agmatine is the presence of a specific cellular uptake mechanism and a specific metabolic enzyme (agmatinase; which forms putrescine).Initially, agmatine was conceptualised as an endogenous clonidine-displacing substance of imidazoline receptors; however, it has now been established to have affinity for several transmembrane receptors, such as alpha(2)-adrenergic, imidazoline I(1) and glutamatergic NMDA receptors. In addition to activity at these receptors, agmatine irreversibly inhibits neuronal nitric oxide synthase and downregulates inducible nitric oxide synthase. Endogenous agmatine is induced in response to stress and/or inflammation. Stressful conditions that induce agmatine include hypoxic-ischaemia and cold-restraint stress of ulcerogenic proportion. Induction of agmatine in the brain seems to occur in astrocytes, although neurons also synthesise agmatine. The effects of injected agmatine in animals include anticonvulsant-, antineurotoxic- and antidepressant-like actions. Intraperitoneal or intracerebroventricular injections of agmatine rapidly elicit antidepressant-like behavioural changes in the rodent forced swim test and tail suspension test. Intraperitoneal injections of agmatine into rats and mice also elicit acute anxiolytic-like behavioural changes in the elevated plus-maze stress test. In an animal model of acute stress disorder, intraperitoneal agmatine injections diminish contextual fear learning. Furthermore, intraperitoneal injections of agmatine reduce alcohol and opioid dependence by diminishing behaviour in a rat conditioned place preference paradigm. Based on these findings, agmatine appears to be an endogenous neuromodulator of mental stress. The possible roles and/or beneficial effects of agmatine in stress-related disorders, such as depression, anxiety and post-traumatic stress disorder, merit further investigation.

Acute toxicity, behavioral changes, and histopathological effects of deltamethrin on tissues (gills, liver, brain, spleen, kidney, muscle, skin) of Nile tilapia (Oreochromis niloticus L.) fingerlings

Deltamethrin, a synthetic pyrethroid contaminating aquatic ecosystems as a potential toxic pollutant, was investigated in the present study for acute toxicity. The purpose of this study was to evaluate LC(50) values of deltamethrin on Nile tilapia (Oreochromis niloticus L.) fingerlings and investigate histopathological responses of fish exposed to deltamethrin. The 48 h LC(50) value for Nile tilapia fingerlings was estimated as 4.85 microg/L using static test system. In addition, behavioral changes at each deltamethrin concentration were observed closely. All fish, exposed to 5 microg/L deltamethrin revealed severe morphological alterations in the gills and liver. In the gills hyperemia, fusion of secondary lamellae and telangiectasis were observed; whereas hydropic degenerations in liver were observed in all examined fish. The results are significant for reporting acute deltamethrin toxicity in terms of behavioral and histopathological changes: Deltamethrin is highly toxic to fingerlings.

Magnetic Resonance Imaging Abnormalities in the Corpus Callosum of a Patient With Neuropsychiatric Lupus

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder which can present with a variety of neurologic and psychiatric complications. Currently, there are no consensus neuroimaging findings associated with neuropsychiatric SLE. We describe the unusual neuroimaging findings in a patient with SLE and a history of epilepsy who presented to a tertiary care emergency department with features of neuropsychiatric lupus, as well as recent seizures. Magnetic resonance imaging of the brain revealed an isolated lesion with T2 signal hyperintensity and restricted diffusion in the midline splenium of the corpus callosum. While establishing the precise etiology underlying the clinical and radiographic observations in this case is difficult, several possibilities are discussed, including acute ischemia and epileptic sequelae. The location of the patient's lesion in a region potentially associated with pure psychotic disorders raises the possibility that such a lesion may be sufficient to produce acute behavior changes and psychotic features in certain patients.

The immunophilin ligand FK506 protects against methamphetamine-induced dopaminergic neurotoxicity in mouse striatum

Repeated use of methamphetamine (MAP) is known to cause neurotoxicity in the dopaminergic neurons of the striatum. Recently, we reported that FK506, a calcineurin inhibitor and immunosuppressive agent, could attenuate acute behavioral changes and the development of sensitization after administration of MAP. In this study, we investigated the effects of FK506 on the neurotoxicity in the dopaminergic neurons induced by repeated administration of MAP. BALB/c mice were injected subcutaneously (s.c.) with vehicle (10 ml/kg) or MAP (4 mg/kg) four times every 2 h. Vehicle (10 ml/kg) or FK506 (0.1, 0.3, 1 or 3 mg/kg i.p.) was administered 15 min before the first MAP administration. Three days later, we assessed the contents of dopamine (DA) and its major metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the mouse striatum using high-performance liquid chromatography (HPLC). We also examined the immunohistochemistry of dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the mouse brain. Repeated administration of MAP decreased significantly the contents of DA and DOPAC in the mouse striatum, and pretreatment with FK506 inhibited significantly the reduction of DA and DOPAC in the mouse brain by repeated administration of MAP. Furthermore, repeated administration of MAP decreased significantly the immunoreactivity of DAT and TH in the striatum as compared to controls. Pretreatment with FK506 (3 mg/kg) attenuated significantly the reduction of DAT and TH immunoreactivity after repeated administration of MAP. These results suggest that FK506 shows protective effects on the MAP-induced neurotoxicity in the dopaminergic neurons of the mouse striatum.

Case Series: Acute Mood Symptoms Associated With Posterior Fossa Lesions in Children

Nineteen children were acutely dysphoric, inattentive, irritable, and sometimes mute following midline posterior fossa neoplasm resection and arteriovenous malformation hemorrhage. These symptoms represent an acute manifestation of the cerebellar cognitive affective syndrome. The authors aimed to describe the acute psychiatric changes in mood and behavior in children with posterior fossa lesions and to evaluate the relationship of posterior fossa syndrome to cerebellar cognitive affective syndrome.

Case Series: Acute Mood Symptoms Associated With Posterior Fossa Lesions in Children

Nineteen children were acutely dysphoric, inattentive, irritable, and sometimes mute following midline posterior fossa neoplasm resection and arteriovenous malformation hemorrhage. These symptoms represent an acute manifestation of the cerebellar cognitive affective syndrome. The authors aimed to describe the acute psychiatric changes in mood and behavior in children with posterior fossa lesions and to evaluate the relationship of posterior fossa syndrome to cerebellar cognitive affective syndrome.

Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.

Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted disruption of the dopamine beta-hydroxylase gene, Dbh, were used to critically test roles for NE in mediating acute behavioral changes elicited by different classes of antidepressants. To this end, we used the tail suspension test, one of the most widely used paradigms for assessing antidepressant activity and depression-related behaviors in normal and genetically modified mice. Dbh(-/-) mice failed to respond to the behavioral effects of various antidepressants, including the NE reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor pargyline, and the atypical antidepressant bupropion, even though they did not differ in baseline immobility from Dbh(+/-) mice, which have normal levels of NE. Surprisingly, the effects of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine were also absent or severely attenuated in the Dbh(-/-) mice. In contrast, citalopram (the most selective SSRI) was equally effective at reducing immobility in mice with and without NE. Restoration of NE by using L-threo-3,4-dihydroxyphenylserine reinstated the behavioral effects of both desipramine and paroxetine in Dbh(-/-) mice, thus demonstrating that the reduced sensitivity to antidepressants is related to NE function, as opposed to developmental abnormalities resulting from chronic NE deficiency. Microdialysis studies demonstrated that the ability of fluoxetine to increase hippocampal serotonin was blocked in Dbh(-/-) mice, whereas citalopram's effect was only partially attenuated. These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs.

Psychoneuroimmunology - mind-brain-immune interactions : mind and body : SAMJ forum

Psychoneuroimmunology (PNI) is the study of interactions between psychological, neuroendocrine and immune processes under basal, disease and therapeutic conditions. It expands the understanding of disease, recognising that psychological phenomena and social context can influence the aetiology and progression of and recovery from illness. While debate continues regarding the way in which intangible mental processes and identifiable physiological ones interact, there can be little argument that these psychological processes require an evolved nervous system, with certain neural networks — identified through imaging studies and neurological disease affecting the mind — related to mental and emotional functions. 1 The extension of the mind/brain relationship to include the immune system is predicated on the presence of multiple neuropeptides and their receptors in cells of the immune system, where they are produced and expressed de novo with high sequence homology to their neuroendocrine relatives, as well as structural links between lymphoid organs and noradrenergic and peptidergic nerve fibres. 2 Furthermore many immunopeptides and their receptors are produced de novo in discrete regions of the brain, most specifically the limbichypothalamic axis, where they may exert a neuromodulatory effect. 2 The functionality of the immune-brain-behavioural pathway has been well described during the acute phase or sickness response. The acute behavioural and physiological changes that regularly accompany infectious illness include, for example, fever, depression, social withdrawal, increased desire for sleep, decreased interest in food and perceptual changes. As part of the immune response to infection, interleukin-1 (IL-1) acts on IL-1 receptors in the vagus nerve and in the brain to mediate such sickness behaviours. 3

Sleep Responses to Light and Dark Are Shaped by Early Experience.

Light regulates sleep timing through circadian entrapment and by eliciting acute changes in behavior. These behaviors are mediated by the subcortical visual system, retinorecipient nuclei distinct from the geniculocortical system. To test the hypothesis that early visual experience shapes light regulation of behavior, the authors recorded sleep in albino rats reared in continuous dark, continuous light, or a 12-hr light-dark cycle. Dark rearing strengthened and light rearing weakened acute responses to light, including light modulation of REM sleep, a marker for pretectal function in albino rats. However, neither dark nor light rearing altered daily amounts of wakefulness, non-REM sleep, or REM sleep. Thus, light and dark rearing might differentially affect the balance between acute and circadian responses to light that, in concert, govern sleep timing.

ENERGY EXPENDITURE, PHYSICAL ACTIVITY, AND OBESITY IN CHILDREN

Although there are physiologic and genetic influences on the various components of energy metabolism and body weight regulation, and a major portion of individual differences in body weight can be explained by genetic differences, it seems unlikely that the increased global prevalence of obesity has been driven by a dramatic change in the gene pool. It is more likely and more reasonable that acute changes in behavior and environment have contributed to the rapid increase in obesity and that genetic factors may be important in the deferring individual susceptibilities to these changes. The most striking behavioral changes that have occurred have been an increased reliance on high-fat and energy-dense "fast foods," with larger portion sizes, coupled with an ever-increasing sedentary lifestyle. The more sedentary lifestyle is caused by an increased reliance on technology and labor-saving devices, which has reduced the need for physical exertion for everyday activities. Examples of energy-saving devices that have resulted in a secular decline in physical activity include: Increased use of automated transport rather than walking or biking Central heating and use of automated equipment, such as washing machines, in the household. Reduction in physical activity in the workplace because of computers, automated equipment, and electronic mail. Increased use of television and computers for entertainment and leisure activities. Use of elevators and escalators rather than stairs. Increased concern for crime, which has reduced the likelihood of outdoor playing. Poor urban planning that does not provide adequate biking paths or even sidewalks in some communities. Thus, the increasing prevalence, numerous health risks, and astounding economic costs of obesity clearly justify widespread efforts toward prevention efforts. These prevention efforts should begin in childhood because the behaviors are learned and continue through the lifetime.

Behavioural, hyperthermic and neurotoxic effects of 3,4-methylenedioxymethamphetamine analogues in the wistar rat

1. The ability of N-ethyl (MDEA) and N-butyl (MDBA) analogues of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) to induce acute behavioural changes and increases in body temperature, and to cause serotonergic neurotoxicity, was assessed in young adult male Wistar rats. The in vitro ability of MDMA analogues to evoke presynaptic monoamine release from crude rat forebrain synaptosomal preparations pre-labelled with [ 3H]5-HT or [ 3H]DA was also measured. 2. In behavioural experiments, acute MDMA and MDEA (20 mg/kg, i.p.) significantly increased rat open-field locomotion scores, decreased open-field rearing, and induced stereotypy, Straub tail and head weaving. MDBA did not produce any of these behaviours. 3. After repeated dosing (8 × 20 mg/kg, i.p., twice daily for 4 days), MDMA > MDEA ⪢ MDBA ≥ saline at decreasing forebrain [ 3H]paroxetine binding levels and concentrations of 5-HT and 5-HIAA at 14 days post-treatment. None of the analogues caused any long-term changes in dopamine or noradrenaline concentrations in the forebrain. 4. Acute MDMA and MDEA (20 mg/kg, i.p.) produced significant acute increases in rat aural temperature compared with saline-treated animals, while 20 mg/kg MDBA caused no significant effects. 5. MDA, MDMA and MDEA were equipotent at inducing [ 3H]5-HT release from frontal cortex/hippocampal synaptosomes, while MDBA only evoked a significant release at 100 μM concentrations. The potency order for inducing [ 3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. 6. This study shows that large N-alkyl substitution decreases the ability of MDMA analogues to evoke presynaptic 5-HT and DA release, induce acute hyperthermia, hyperlocomotion and behavioural changes, and cause long-term serotonergic neurotoxicity. 7. The structure-activity relationship data presented here indicate that the neurotoxic damage caused by substituted amphetamines requires a combination of acute hyperthermia and increased neurotransmitter release. Induction of one of these effects in isolation is not sufficient to cause serotonergic nerve terminal degradation.

Neuropsychiatric and neuropsychological manifestations of central pontine myelinolysis

A patient with central pontine myelinolysis (CPM) underwent neurological and mental status examination, as well as neuropsychological testing, during the acute stage of the disease. After correction of the hyponatremia, a gross change in his neuropsychiatric status was observed. The patient underwent extensive neurological, psychiatric, and neuropsychological testing during the acute phase of the disease and at follow-up 4 months later. All major neurological and neuropsychiatric symptoms present at onset were fully reversible. Neuropsychological examination revealed deficits in the domains of attention and concentration, short-term memory and memory consolidation, visual motor and fine motor speeds, and learning ability. Although improved, neuropsychological testing still revealed remarkable deficits at follow-up. We conclude that neuropsychological deficits can accompany CPM, and that these deficits do not necessarily diminish simultaneously with the radiological or clinical neurological findings but may persist for a longer period of time, or even become permanent. In his recovery the patient started to manifest new neurological symptoms consisting of a mild resting tremor of both hands and slow choreoathetotic movements of the trunk and the head, which we considered to be late neurological sequelae of CPM. The significance of CPM in the differential diagnosis of acute behavioral changes after correction of hyponatremia is stressed, even if correction is achieved slowly and carefully.

Intoxication by Non-Protein Nitrogen Compounds In Rat Feed

ABSTRACTLast year our white rats (Wistar origin) showed acute behavioral and physiological changes followed by death in 70% of the animals. We detected that the malfunctions could be attributed to the new batch of laboratory rat pellets provided two weeks before. High levels of urea (260 mg/kg) and ammonia (540 mg/kg) were found in the feed while usual values in other similar feed were 48 mg/kg and 82 mg/kg respectively. Suspecting an ammonia intoxication, concentrations of ammonia and urea were determined in blood, brain and liver. Brain neurotransmitters and blood tryptophan and serotonine (5-HT) were also determined. Blood ammonia in rats fed the contaminated feed was about 100% higher than those fed the normal feed while liver and brain ammonia were three and four fold high respectively. Liver and brain urea were four to five fold and about 100% higher in the exposed group than in the group fed the control diet respectively. Blood 5-HT increased 62.33% in females and 99% in males whereas brain 5-HT increased 83.13% in females and 70.47% in males. But, we detected a 59.8% decrease in brain dopamine levels in females and a 38.65% decrease in males. Liver histology showed small droplets of fat stores mainly in centrolobular hepatocyte. No differences in blood or liver cholesterol concentrations were observed whereas liver triacylglycerides were significantly higher in intoxicated females. This study illustrates a problem of food borne intoxication that justifies the need for exhaustive analyses of even not usual compounds in every feed batch; moreover, it is demonstrated that rat behavior appears to be the earliest biomarker of ammonia exposure.

Adaptation of the fluid percussion injury model to the mouse.

Fluid percussion injury (FPI) is a well-characterized experimental model of traumatic brain injury (TBI) in the rat. Many pathophysiologic consequences and mechanisms of recovery after TBI rely on neurochemical pathways that can be examined in genetically altered mice. Therefore, FPI applied to mice may be a useful experimental tool to investigate TBI at the molecular level. In the present study, we establish FPI as a viable model of TBI in the mouse by characterizing acute neurological, histopathological, and behavioral changes. Right-sided parasagittal FPI or sham treatment was administered in male C57BL/6 mice. Acute neurological evaluation revealed righting reflexes in the injured animals (p < 0.001). Deficits in spatial learning and memory were observed in the Morris water maze (MWM) 5 and 6 days after injury. A novel MWM data analysis protocol is described. The injured group (n = 18) demonstrated impaired performance in the MWM during acquisition (p < 0.05) and probe trials (p < 0.025) compared to sham animals (n = 16). At 7 days postinjury, glial fibrillary acidic protein immunohistochemistry revealed intense cortical, callosal, and hippocampal gliosis. The modified Gallyas silver degeneration stain consistently labeled cell bodies and terminals throughout the ipsilateral cortex, axons in the gray matter-white matter interface above the corpus callosum and within the corpus callosum bilaterally, and terminals and fibers in the thalamus bilaterally. Additionally, the mouse FPI model described is immediately employable in labs already using the FPI rat model with no modifications to a pre-existing FPI apparatus.

Neuroprotective effects of the strychnine-insensitive glycine site NMDA antagonist ( R)-HA-966 in an experimental model of Parkinson's disease

The neuroprotective effects of ( R)-HA-966 and ( S)-HA-966 (3-amino-1-hydroxy-2-pyrrolidinone) were examined in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced animal model of Parkinson's disease. Systemic pretreatment of C57 black mice with the strychnine-insensitive glycine site antagonist, ( R)-HA-966 (3-30 mg/kg, i.p.), dose-dependently attenuated MPTP-induced depletion of striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC). Pretreatment with ( R)-HA-966 also significantly protected the degeneration of tyrosine hydroxylase-positive neurons in the substantia nigra of mice treated with MPTP and alleviated the acute behavioral changes caused by the neurotoxin. In contrast, the other racemic form, ( S)-HA-966, neither prevented the neurochemical depletions nor the neuronal injury caused by MPTP. These results indicate that excitatory mechanisms of neurodegeneration are involved in the pathophysiology of Parkinson's disease, and that strychnine-insensitive glycine site NMDA antagonists may serve as dopaminoprotective agents which intervene in the progressive neurodegeneration in Parkinson's disease.

Affective disorders following stroke.

Numerous studies in stroke patients suggest that the left frontal anterior region may be strategic for depression. However, these findings could not always be replicated. Some authors even deny any etiological contribution of lesion location to depression. The predominant role of the right hemisphere in secondary mania is well recognized. In disorders such as apathy, anxiety, catastrophe reactions and pathological laughing and crying, further studies are needed to determine the potential clinico-topographic correlations. Affective disorders are important to consider in stroke patients, since they may influence neurological recovery and may be responsive to treatment. Remarkable features of emotional behavior, such as disinhibition, denial, indifference, overt sadness and aggressiveness, are not rare during the acute phase of stroke and might be overlooked if not searched for systematically with appropriately designed scales. Some of these early behaviors, such as denial, may relate to the late development of depression, anxiety and other disorders. Systematic studies on large samples of patients may allow to establish which of these acute emotional behavioral changes are markers for the delayed development of mood disorders.

Case Report: Sometimes a Cigar is just a Cigar

This unusual case underscores the need for psychiatrists to consider treatable and curable causes of acute behavior changes even when historical data are not easily available. This case presentation invites physicians of mind (and body) to utilize simple and common-sense approaches while evaluating their patients.

Emergency pharmacotherapy: the evolving role of medications in the emergency department.

AbstractThe dual roles of psychiatric medications in the emergency department are reviewed; established and new approaches to the pharmacotherapy of acute behavioral changes are described.

Intracerebroventricular injection of corticotropin-releasing hormone in the pig: acute effects on behavior, adrenocorticotropin secretion, and immune suppression.

Corticotropin-releasing hormone (CRH) has been implicated as an important mediator of behavior, immune, and neuroendocrine systems in animals experiencing stress, but its effects on these systems have not been evaluated in an integrated whole animal model. In this experiment we injected porcine and rat CRH (pCRH and rCRH) intracerebroventricularly (icv) and simultaneously and chronologically monitored acute changes in behavior, endocrine, and immune function in the pig. PBS or CRH (15, 50, and 150 micrograms pCRH and 15 and 150 micrograms rCRH) was injected icv, and serial blood samples were collected via an indwelling jugular catheter so that behavior could be monitored simultaneously. The central administration of pCRH and rCRH induced immediate dose-dependent behavioral and physiological responses. Pigs receiving 15 micrograms of either pCRH or rCRH had increased plasma ACTH and were hyperactive and vocal. However, when higher doses (i.e. 50 or 150 micrograms) were administered icv, the endocrine and behavioral responses were accompanied by a profound suppression of Concanavalin-A-induced lymphocyte proliferation. For example, pigs receiving 150 micrograms pCRH had increased plasma ACTH and motor activity at 10 min (P < 0.01) and suppressed lymphocyte proliferation at 30 min (P < 0.001). Whereas ACTH secretion declined after 40 min, the lymphocyte suppression and increased motor activity were sustained, suggesting different control mechanisms. It is suggested that although ACTH and cortisol may have negative feedback effects on ACTH secretion, they did not have these effects on the behavioral action of CRH. Furthermore, although the lowest dose of CRH (15 micrograms) induced motor activity and ACTH secretion, higher doses (50 or 150 micrograms) were necessary for suppression of mitogen-induced lymphocyte proliferation. These findings demonstrate that CRH in the pig brain is active for inducing simultaneous changes in behavioral and physiological systems and are, therefore, consistent with the hypothesis that brain CRH is important in mediating the interaction among behavior, endocrine, and immune systems in animals experiencing stress.

Neuropathologic and morphometric effects of aminoguanidine on rat nerves

Aminoguanidine prevents some pathophysiologic changes typical of streptozocin diabetes and, therefore, might be efficacious in prevention or treatment of human diabetic polyneuropathy. In order to evaluate the possible toxicity of aminoguanidine on peripheral nerves, Sprague-Dawley rats received aminoguanidine intraperitoneally in dosages of 0, 50, 100, and 300 mg/kg per day for 3 months. Only rats receiving the highest dosages developed acute and chronic behavioral changes and had decreased weight gain. Minor hepatic dysfunction also was observed in this group. Teased-fiber abnormalities were not significantly more frequent in the highest dosage group than in controls. Likewise, a significant morphometric abnormality was not found for the peroneal nerve. Mild changes were found in the highest dosage group compared to the control group in the sural nerve (increased fiber density, decreased myelin area). We interpret the small morphometric differences for the sural nerve as due to maldevelopment. We found no evidence that aminoguanidine at a high dosage (300 mg/kg per day) caused fiber degeneration or demyelination.