Behavior In Animal Models Research Articles

Peroxisome proliferator-activated receptor gamma co-activator-1 alpha in depression and the response to electroconvulsive therapy.

The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC-1α), termed the 'master regulator of mitochondrial biogenesis', has been implicated in stress and resilience to stress-induced depressive-like behaviours in animal models. However, there has been no study conducted to date to examine PGC-1α levels in patients with depression or in response to antidepressant treatment. Our aim was to assess PGC-1α mRNA levels in blood from healthy controls and patients with depression pre-/post-electroconvulsive therapy (ECT), and to examine the relationship between blood PGC-1α mRNA levels and clinical symptoms and outcomes with ECT. Whole blood PGC-1α mRNA levels were analysed in samples from 67 patients with a major depressive episode and 70 healthy controls, and in patient samples following a course of ECT using quantitative real-time polymerase chain reaction (qRT-PCR). Exploratory subgroup correlational analyses were carried out to determine the relationship between PGC-1α and mood scores. PGC-1α levels were lower in patients with depression compared with healthy controls (p = 0.03). This lower level was predominantly accounted for by patients with psychotic unipolar depression (p = 0.004). ECT did not alter PGC-1α levels in the depressed group as a whole, though exploratory analyses revealed a significant increase in PGC-1α in patients with psychotic unipolar depression post-ECT (p = 0.045). We found no relationship between PGC-1α mRNA levels and depression severity or the clinical response to ECT. PGC-1α may represent a novel therapeutic target for the treatment of depression, and be a common link between various pathophysiological processes implicated in depression.

Resveratrol and Depression in Animal Models: A Systematic Review of the Biological Mechanisms.

Depression is currently treated by pharmacotherapies that can elicit debilitating side effects for patients. Novel treatment options with limited side effects are currently being researched. Resveratrol is a polyphenol and phytoalexin found in the skins of grapes, red wine, Japanese knotweed, and peanuts. It has been studied extensively for its antioxidant and anti-inflammatory properties. Resveratrol has also gained attention for its neuroprotective properties. The aim of the review was to examine the mechanisms by which resveratrol reduces depressive behaviors in animal models. In total, 22 studies met the established criteria for final review. Behavioral aspects of depression were investigated using validated measures such as the forced swimming test, tail suspension test, sucrose preference test, and open field test. While many physical measures were taken, three main biological mechanisms were explored: Regulation of the hypothalamic–pituitary–adrenal axis; decreased inflammation; and increased Brain-Derived Neurotrophic Factor and neurogenesis. Based on these findings, resveratrol may be deemed an effective treatment for depression in animal models at doses between 10–80 mg/kg/day, although higher doses had the most significant effects. Future studies should examine the effects of resveratrol on depression in humans to determine the eligibility of resveratrol as a natural antidepressant with less severe side effects.

Association study of Disrupted-In-Schizophrenia-1 gene variants and tardive dyskinesia

Tardive dyskinesia (TD) is an involuntary movement disorder that occurs in ∼20% of patients after extended antipsychotic use. Its pathophysiology is unclear; however, familial patterns and gene association studies indicate an inherited component to risk. The disrupted in schizophrenia 1 (DISC1) gene was selected for analysis because it interacts with and regulates two important proteins involved in antipsychotic medication action: the dopamine D2 receptor and the cAMP phosphodiesterase type IVB (PDE4B). The D2 receptor is the obligate target of all existing antipsychotic medications, and PDE4B hydrolyzes cAMP, a core signaling molecule activated by agonist binding to the D2 receptor. Notably, PDE4B inhibitors such as rolipram have been shown to reduce TD-like behaviours in animal models. Nine single-nucleotide polymorphisms (SNPs) in the DISC1 gene were investigated in a sample of 193 chronic schizophrenia patients for association with the presence and severity of TD, with age and sex as additional variables. TD severity was measured using the Abnormal Involuntary Movement Scale (AIMS). Two DISC1 SNPs were associated with TD severity (uncorrected p < 0.05), but these findings did not survive correction for multiple testing. This preliminary investigation suggests that DISC1 gene variants do not affect risk for TD or severity.

The role of hippocampal adult neurogenesis in methamphetamine addiction.

One of the consequences of chronic methamphetamine (Meth) abuse and Meth addiction is impaired hippocampal function which plays a critical role in enhanced propensity for relapse. This impairment is predicted by alterations in hippocampal neurogenesis, structural- and functional-plasticity of granule cell neurons (GCNs), and expression of plasticity-related proteins in the dentate gyrus. This review will elaborate on the effects of Meth in animal models during different stages of addiction-like behavior on proliferation, differentiation, maturation, and survival of newly born neural progenitor cells. We will then discuss evidence for the contribution of adult neurogenesis in context-driven Meth-seeking behavior in animal models. These findings from interdisciplinary studies suggest that a subset of newly born GCNs contribute to context-driven Meth-seeking in Meth addicted animals.

Evidence of Reduced Agmatine Concentrations in the Cerebral Cortex of Suicides.

BackgroundThe polyamines are a group of ubiquitous low-molecular–weight aliphatic molecules that play an essential role in various physiological functions of the mammalian CNS. Previous literature has indicated alterations in the expression of polyamine-related genes in the brains of individuals who died by suicide, including downregulation of spermidine/spermine N1-acetyltransferase, a key enzyme involved in polyamine catabolism. One such polyamine, agmatine, has been shown to act as an antidepressant in animal models of depressive-like behavior. However, agmatine concentrations have not been explored in postmortem human brain of individuals who died by suicide.MethodsTo measure agmatine in postmortem human brain tissue, we employed our previously published high-resolution capillary gas chromatography in combination with mass spectrometry method. Using this method, we analyzed agmatine levels in a total of 120 tissue samples from Brodmann areas 4, 11, and 44 of 40 male subjects comprising controls (n=13), individuals who died by suicide and met criteria for major depressive disorder (n=14), and subjects who died by suicide and did not meet criteria for major depressive disorder (n=13).ResultsAgmatine fell within the expected nanomolar range and was significantly reduced in the cortex of suicides, irrespective of meeting criteria for major depressive disorder compared with controls.ConclusionsThis is the first gas chromatography-mass spectrometry study to analyze agmatine concentrations in human postmortem brain of individuals who died by suicide. These results add to our mechanistic understanding of the role that the polyamine stress response pathway may play in the neurobiology of major depression and/or suicide.

Design, synthesis and pharmacological evaluation of carboxamide and carbothioamide derivatives of 1,3,4-thiadiazole as the inhibitors of acetylcholinesterase and oxipiperazine)ative stress for the management of cognitive debility

Acetylcholinesterase has been a promising target for the development of putative therapeutics against cognitive decline. The deleterious effect of oxidative stress on the learning and memory paradigms of an individual has also been well documented. In view of this and our previous findings on the ameliorative effects of amide derivatives of 1,3,4-thiaidiazoles on cognitive deterioration, the present study demonstrated the design, synthesis and pharmacological evaluation of carboxamides and carbothioamide derivatives of 1,3,4-thiadiazole. Novel carboxamide and carbothioamide derivatives were synthesised and characterised by various spectral and elemental techniques. Their effects on memory were studied by employing scopolamine induced amnesia in two behavioural animal models: Morris water maze and passive avoidance (dose of 0.5 mg/kg) with reference to the standard, Rivastigmine. In vitro AChE inhibition was studied at five different concentrations using the homogenised fraction of the decapitated mice brain as the source of the enzyme. Biochemical estimation of AChE, oxidative and nitrosative stress parameters have also been facilitated. Computational docking studies have been performed on human recombinant AChE (PDB ID: 4EY7) to assess the binding conformation of the molecules. The results indicated that the carbothioamide analogues 13a, 9b and 10b were found to be the most promising in the alleviation of cognitive decline induced by scopolamine. Among the carboxamide analogues, 8b has shown promising effect in the alleviation of cognition decline. Our results suggested the possible role of these derivatives in the mediation of cholinergic pathway and attenuation of oxidative stress resulting in the effective management of cognitive dysfunction.

Advances in behavioral animal models of alcohol use disorder.

Alcohol use disorder (AUD) is a multifaceted neuropsychiatric disease that combines behavioral, psychosocial, and neurobiological aspects. Over the previous decade, animal models have advanced in modeling the major psychological constructs that characterize AUD. These advances pave the road for more sophisticated behavioral models that capture addiction-related aspects, such as alcohol craving, compulsive seeking and intake, dependence, and relapse. In this review, we survey the recent progress in behavioral animal modeling of five aspects of AUD: alcohol consumption, dependence, and seeking; compulsivity in alcohol intake despite adverse outcomes; vulnerability and resilience factors in alcohol addiction; relapse despite treatment; and relapse prevention by manipulating alcohol-associated memory reconsolidation. These advances represent a general attempt to grasp the complexity and multidimensional nature of AUD, and to focus on behavioral characteristics that better reflect and model this disorder.

Mouse Strain Affects Behavioral and Neuroendocrine Stress Responses Following Administration of Probiotic Lactobacillus rhamnosus JB-1 or Traditional Antidepressant Fluoxetine.

Currently, there is keen interest in the development of alternative therapies in the treatment of depression. Given the explosion of research focused on the microbiota-gut-brain axis, consideration has turned to the potential of certain probiotics to improve patient outcomes for those suffering from mood disorders. Here we examine the abilities of a known antidepressant, fluoxetine, and the probiotic Lactobacillus rhamnosus JB-1™, to attenuate responses to two established criteria for depressive-like behavior in animal models, the tail suspension test (TST) and the corticosterone response to an acute restraint stressor. We examine two different strains of mice known to differ in the extent to which they express both anxiety-like behavior and measures of despair—BALB/c and Swiss Webster—with respectively high and normal behavioral phenotypes for each. While adult male BALB/c mice responded with increased antidepressive-like behavior to both fluoxetine and L. rhamnosus JB-1 in both the TST and the corticosterone stress response, SW mice did not respond to either treatment as compared to controls. These findings highlight the importance of investigating putative antidepressants in mouse strains known to express face validity for some markers of depression. Clinical studies examining the activity of L. rhamnosus JB-1 in patients suffering from mood disorders are warranted, as well as further pre-clinical work examining how interactions between host genotype and intestinal microbial alterations may impact behavioral responses. This study adds to the literature supporting the possibility that modifying the intestinal microbiota via probiotics represents a promising potential therapeutic breakthrough in the treatment of psychiatric disease.

Relevance of Rodent Models of Depression in Clinical Practice: Can We Overcome the Obstacles in Translational Neuropsychiatry?

The diagnosis of a mental disorder generally depends on clinical observations and phenomenological symptoms reported by the patient. The definition of a given diagnosis is criteria based and relies on the ability to accurately interpret subjective symptoms and complex behavior. This type of diagnosis comprises a challenge to translate to reliable animal models, and these translational uncertainties hamper the development of new treatments. In this review, we will discuss how depressive-like behavior can be induced in rodents, and the relationship between these models and depression in humans. Specifically, we suggest similarities between triggers of depressive-like behavior in animal models and human conditions known to increase the risk of depression, for example exhaustion and bullying. Although we acknowledge the potential problems in comparing animal findings to human conditions, such comparisons are useful for understanding the complexity of depression, and we highlight the need to develop clinical diagnoses and animal models in parallel to overcome translational uncertainties.

Characterization of a Novel Series of D4 Dopamine Receptor Ligands Reveals Structure‐Activity Relationships for Selective Partial Agonists

D4 dopamine receptors (D4R) are G protein‐coupled receptors that play important roles in cognition, attention, and decision making. D4R ligands have been shown to alter cognition and behavior in animal models of drug addiction and variations in the DRD4 gene have been associated with novelty‐seeking and risk behavior, as well as ADHD. A better understanding of D4R‐mediated signaling is essential to understanding and treating D4R‐associated disorders, including substance abuse disorders. Despite its clinical implications, there are currently few compounds that selectively modulate the D4R receptor. Such compounds are important to study D4R function and identify favorable pharmacology for disease treatment. We created a small next‐generation compound library using computational modelling to design D4R ligands based on the parental scaffold of the prototypical D4R partial agonist A‐412997. This library was analyzed for D2R, D3R, and D4R activity using both agonist and antagonist radioligand competition binding assays and functional signaling readouts (β‐arrestin recruitment and cAMP inhibition). We found that substitutions on the piperidine and pyridine moieties, as well as modifications in linker length, led to several novel lead compounds with improved selectivity and potency, and varying degrees of agonist efficacy. Compounds were identified that displayed high binding affinity (&lt;100 nM) for the D4R coupled with a &gt;1000‐fold selectivity vs. the D3R and D2R. Importantly, these ligands displayed a range of agonist efficacies from highly efficacious partial agonists to full antagonists of the D4R. Interestingly, some compounds with similar binding affinities showed divergent functional efficacies, allowing for the generation of a preliminary structure‐activity relationship underlying functional efficacy. Further optimization may allow for directed tuning of functional efficacy that, when coupled to in vivo behavioral studies, may provide insight into the importance of relative efficacy levels as a means to treat D4R‐related disorders.Support or Funding InformationNINDS IRPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Probabilistic models of individual and collective animal behavior

Recent developments in automated tracking allow uninterrupted, high-resolution recording of animal trajectories, sometimes coupled with the identification of stereotyped changes of body pose or other behaviors of interest. Analysis and interpretation of such data represents a challenge: the timing of animal behaviors may be stochastic and modulated by kinematic variables, by the interaction with the environment or with the conspecifics within the animal group, and dependent on internal cognitive or behavioral state of the individual. Existing models for collective motion typically fail to incorporate the discrete, stochastic, and internal-state-dependent aspects of behavior, while models focusing on individual animal behavior typically ignore the spatial aspects of the problem. Here we propose a probabilistic modeling framework to address this gap. Each animal can switch stochastically between different behavioral states, with each state resulting in a possibly different law of motion through space. Switching rates for behavioral transitions can depend in a very general way, which we seek to identify from data, on the effects of the environment as well as the interaction between the animals. We represent the switching dynamics as a Generalized Linear Model and show that: (i) forward simulation of multiple interacting animals is possible using a variant of the Gillespie’s Stochastic Simulation Algorithm; (ii) formulated properly, the maximum likelihood inference of switching rate functions is tractably solvable by gradient descent; (iii) model selection can be used to identify factors that modulate behavioral state switching and to appropriately adjust model complexity to data. To illustrate our framework, we apply it to two synthetic models of animal motion and to real zebrafish tracking data.

Low-Frequency rTMS Ameliorates Autistic-Like Behaviors in Rats Induced by Neonatal Isolation Through Regulating the Synaptic GABA Transmission.

Patients with autism spectrum disorder (ASD) display abnormalities in neuronal development, synaptic function and neural circuits. The imbalance of excitatory and inhibitory (E/I) synaptic transmission has been proposed to cause the main behavioral characteristics of ASD. Repetitive transcranial magnetic stimulation (rTMS) can directly or indirectly induce excitability and synaptic plasticity changes in the brain noninvasively. However, whether rTMS can ameliorate autistic-like behaviors in animal model via regulating the balance of E/I synaptic transmission is unknown. By using our recent reported animal model with autistic-like behaviors induced by neonatal isolation (postnatal days 1–9), we found that low-frequency rTMS (LF-rTMS, 1 Hz) treatment for 2 weeks effectively alleviated the acquired autistic-like symptoms, as reflected by an increase in social interaction and decrease in self-grooming, anxiety- and depressive-like behaviors in young adult rats compared to those in untreated animals. Furthermore, the amelioration in autistic-like behavior was accompanied by a restoration of the balance between E/I activity, especially at the level of synaptic transmission and receptors in synaptosomes. These findings indicated that LF-rTMS may alleviate the symptoms of ASD-like behaviors caused by neonatal isolation through regulating the synaptic GABA transmission, suggesting that LF-rTMS may be a potential therapeutic technique to treat ASD.

Alterations in mGlu5 receptor expression and function in the striatum in a rat depression model.

Major depressive disorder is a common form of mental illness. Many brain regions are implicated in the pathophysiology and symptomatology of depression. Among key brain areas is the striatum that controls reward and mood and is involved in the development of core depression-like behavior in animal models of depression. While molecular mechanisms in this region underlying depression-related behavior are poorly understood, the glutamatergic input to the striatum is believed to play a role. In this study, we investigated changes in metabotropic glutamate (mGlu) receptor expression and signaling in the striatum of adult rats in response to prolonged (10-12weeks) social isolation, a pre-validated animal paradigm modeling depression in adulthood. We found that mGlu5 receptor protein levels in the striatum were increased in rats that showed typical depression- and anxiety-like behavior after chronic social isolation. This increase in mGlu5 receptor expression was seen in both subdivisions of the striatum, the nucleus accumbens and caudate putamen. At subcellular and subsynaptic levels, mGlu5 receptor expression was elevated in surface membranes at synaptic sites. In striatal neurons, the mGlu5-associated phosphoinositide signaling pathway was augmented in its efficacy after prolonged social isolation. These data indicate that the mGlu5 receptor is a sensitive substrate of depression. Adulthood social isolation leads to the up-regulation of mGlu5 receptor expression and function in striatal neurons.

Sacred Maya incense, copal (Protium copal - Burseraceae), has antianxiety effects in animal models

Ethnopharmacological relevanceThe Maya have traditionally used copal, Protium copal, as incense during ceremonies since pre-Columbian times. Anecdotally, copal (when burned as incense), is thought to elicit mentally uplifting and calming effects. The main objective of this study was to determine whether the incense elicits anxiolytic-like behavior in animal models using rats. A second objective was to characterize active constituents and discern potential mechanism(s) of action, specifically the involvement of the GABAergic and endocannabinoid (eCB) systems. Despite the extensive Central American use of this resin, there are currently no known scientific behavioral or pharmacological studies done with the incense. Materials and methodsQuantification of the triterpenes in the copal resin and cold trapped incense was achieved by HPLC MS. Behavioral effects in rats were assessed using the elevated plus maze (EPM), social interaction (SI) test, conditioned emotion response (CER) and Novel object recognition (NOR) paradigms. Rats were exposed to burning copal (200 mg) over 5 min in a smoking chamber apparatus and then immediately tested in each behavioral paradigm. Follow-up SI tests were done using two antagonists flumazenil (1 mg/kg) and AM251 (1 mg/kg) administered systemically. Inhibition of MAGL (monoacylglycerol lipase) was measured by microplate assay with recombinant human enzyme and probe substrate. ResultsPhytochemical analysis revealed that copal resin and incense had high α- and β-amyrins and low lupeol triterpene content. Exposure to Protium copal incense significantly reduced anxiety-like behavior in the SI and CER tests. In contrast, no anxiolytic effects were observed in the EPM. The CER effect was time dependent. Both flumazenil and AM251 blocked the anxiolytic activity of copal revealing the involvement of GABAergic and endocannabinoid systems. Copal, as well as the identified triterpenes, potently inhibited monoacylglycerol lipase (MAGL) activity in vitro (IC50 ≤ 811 ng/mL). ConclusionsThis is the first study to show that copal incense from Protium copal elicits anxiolytic-like effects in fear and social interaction models as evidenced by a reduced learned fear behavior and an increase in active social interaction. It's high α and β-amyrin content suggests behavioral effects may be mediated, in part, by the known action of these terpenes at the benzodiazepine receptor. Furthermore, P. copal's observed activity through the eCB system via MAGL offers a new potential mechanism underlying the anxiolytic activity.

The sigma-1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction.

Methamphetamine (METH) abuse is a major public health issue around the world, yet there are currently no effective pharmacotherapies for the treatment of METH addiction. METH is a potent psychostimulant that increases extracellular dopamine levels by targeting the dopamine transporter (DAT) and alters neuronal activity in the reward centers of the brain. One promising therapeutic target for the treatment of METH addiction is the sigma-1 receptor (σ1R). The σ1R is an endoplasmic reticulum-localized chaperone protein that is activated by cellular stress, and, unique to this chaperone, its function can also be induced or inhibited by different ligands. Upon activation of this unique "chaperone receptor", the σ1R regulates a variety of cellular functions and possesses neuroprotective activity in the brain. Interestingly, a variety of σ1R ligands modulate dopamine neurotransmission and reduce the behavioral effects of METH in animal models of addictive behavior, suggesting that the σ1R may be a viable therapeutic target for the treatment of METH addiction. In this review, we provide background on METH and the σ1R as well as a literature review regarding the role of σ1Rs in modulating both dopamine neurotransmission and the effects of METH. We aim to highlight the complexities of σ1R pharmacology and function as well as the therapeutic potential of the σ1R as a target for the treatment of METH addiction.

The anxiolytic effect of Juniperus virginiana L. essential oil and determination of its active constituents

Essential oil from Juniperus virginiana L. (eastern red cedarwood essential oil, CWO) has been used to relax mind and enhance comfort for medical purposes. Few reports showed its effect on anxiety behaviors in animal models. The present study investigated the anxiolytic effect of CWO using two anxiety tests in mice, then determined the major active constituents, examined the change of neurotransmitters after intraperitoneal (i.p.) administration. Analysis using GC/MS revealed that the CWO contained (-)-α-cedrene (28.11%), (+)-β-cedrene (7.81%), (-)-thujopsene (17.71%) and (+)-cedrol (24.58%). CWO at 400–800mg/kg increased the percentage of open arm entries and the percentage of the time spent in open arms in the elevated plus maze (EPM), suggesting that the oil has anxiolytic effect. However, it didn't show anxiolytic effect in the light-dark box (LDB) test. Tests of the cedrene did not show anxiolytic effect in either test, but rather induced anxiety-related behaviors and inhibited the locomotor activity in EPM and LDB. Cedrol produced significant anxiolytic effect in both EPM and LDB tests at 400–1600mg/kg and 800–1600mg/kg, respectively. A more significant increase in locomotor activity was observed in cedrol at 200–1600mg/kg administration than CWO. CWO increased the 5-hydroxytryptamine (5-HT) concentration at 800mg/kg, whereas it didn't affect the dopamine (DA) concentration. Cedrol significantly reduced the DA level at 100-200mg/kg and elevated the 5-HT level at 1200–1600mg/kg. Moreover, it changed the ratio of 5-hydroxyindoleacetic acid/5-HT and 3, 4-dihydroxyphenyl acetic acid/DA at 1200–1600mg/kg. CWO and cedrol, in particular might act in an anxiolytic effect through the 5-HTnergic and DAnergic pathways.

Progress in Epigenetics of Depression.

Depression is a prevalent and complex psychiatric syndrome. Epigenetic mechanisms bridge the genetic and environmental factors that contribute to the pathophysiology of depression. A surge of research over the last decade has identified changes in DNA methylation, histone modifications, histone organization, and noncoding RNAs associated with depression and stress-induced depression-like behavior in animal models. We focus here on associations of epigenetic factors concurrent with depression and depression-like behavior, although risk for depression and some of the associated epigenetic changes are known to have developmental origins. Finally, emerging technology may enable breakthroughs in the ability to rescue depression-associated epigenetic modifications at specific genes, greatly enhancing specificity of future potential therapeutic treatments.

Modeling Complex Neurological Diseases with Stem Cells: A Study of Bipolar Disorder.

The pathogenesis of bipolar disorder (BPD) is unknown. Using human-induced pluripotent stem cells (hiPSCs) to unravel pathological mechanisms in polygenic diseases is challenging, with few successful studies to date. However, hiPSCs from BPD patients responsive to lithium have offered unique opportunities to discern lithium's mechanism of action and hence gain insight into BPD pathology. By profiling the proteomics of BPD-hiPSC-derived neurons, we found that lithium alters the phosphorylation state of collapsin response mediator protein-2 (CRMP2). The "set point" for the ratio of pCRMP2:CRMP2 is elevated uniquely in hiPSC-derived neurons from lithium responsive (Li-R) BPD patients, but not other psychiatric and neurological disorders. Utilizing neurons differentiated from human patient stem cells as an in vitro platform, we were abletoelucidate the mechanism driving the pathogenesis and pathophysiology of lithium-responsive BPD, heretofore unknown.Importantly, the findings in culture werevalidated in human postmortemmaterial as well as in animal models of BPD behavior. These data suggest that the "lithium response pathway" in BPD governs CRMP2's phosphorylation, which regulates cytoskeletal organization, particularly in dendritic spines, leading to modulated neural networks that may underlie Li-R BPD pathogenesis. This chapter reviews the methodology of leveraging a functional agent, lithium, to identify unknown pathophysiological pathways with hiPSCs and how to translate this disease modeling approach to other neurological disorders.

Mindreading in the Animal Kingdom: Philosophical Controversies

The central issue in the debate on animal minds is the issue of mindreading. This complicated cognitive ability belongs to the key elements of social cognition—as a form of adapting to specific circumstances connected with living in groups, it enables the reading of the mental states of other individuals, e.g. intentions, desires, and beliefs as well as the adaptation of one’s own behavior to this information. The primary purpose of the article is to present the main philosophical controversies which arise in the discussion of whether this ability can be attributed to animals; if so, then to what extent. Philosophical discussions concentrate on methodological issues: alternative interpretational models of animal behavior (mindreading vs reading behavior), anthropomorphism, experimental protocols, and gradeability of mindreading as well as the nature of the mind (thinking).

Potential effect of spermidine on GABA, dopamine, acetylcholinesterase, oxidative stress and proinflammatory cytokines to diminish ketamine-induced psychotic symptoms in rats

Ketamine, N-methyl-d-aspartate receptor antagonist has been implanted in such behavioural and biochemical alterations in animals similar to human psychosis. Spermidine, a biogenic polyamine, involved in various cellular functions in living organisms, on the contrary possess NMDA receptor agonistic effect. Therefore, we aimed to study the effect of spermidine (10 and 20 mg/kg, i.p.) in ketamine (50 mg/kg, i.p.) induced psychotic symptoms using various behavioural animal models. Biochemical assays were done to confirm the molecular pathways associated with spermidine and psychosis. Spermidine was significant to alleviate the ketamine-induced psychotic symptoms as indicated by decrease in locomotor activity in actophotometer, stereotypic behaviours, immobility duration in force swim test and latency to climb the pole in pole climb avoidance test. Interestingly, spermidine significantly decreased acetylcholinesterase (AChE) activity, serum tumor necrosis factor (TNF-α), dopamine and malondialdehyde (MDA) level while increased gamma-amino butyric acid and reduced glutathione (GSH) level in different regions of brain. Spermidine did not produce cataleptic effect on bar test at lower dose, but at the higher dose its cataleptic effect was similar to haloperidol. Based on behavioural and biochemical results, present study revealed spermidine as a promising antipsychotic biomolecule, however, its cataleptic effect at higher doses must be ruled out before use in clinical settings.