Perfectionism-suppression based animal model of depression

Suppression of perfectionism-like behaviors in animals might psychologically mimic human depression, thus creating new animal models of mood disorders.     

The antidepressant-like effect of Ocimum basilicum in an animal model of depression

We investigated the efficacy of Ocimum basilicum (OB) essential oils for treating depression related behavioral, biochemical and histopathological changes caused by exposure to chronic unpredictable mild stress (CUMS) in mice and to explore the mechanism underlying the pathology. Male albino mice were divided into four groups: controls; CUMS; CUMS plus fluoxetine, the antidepressant administered for pharmacological validation of OB; and CUMS plus OB. Behavioral tests included the forced swim test (FST), elevated plus-maze (EPM) and the open ?eld test (OFT); these tests were performed at the end of the experiment. We assessed serum corticosterone level, protein, gene and immunoexpression of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) as well as immunoexpression of glial fibrillary acidic protein (GFAP), Ki67, caspase-3 in the hippocampus. CUMS caused depression in the mice as evidenced by prolonged immobility in the FST, prolonged time spent in the open arms during the EPM test and reduction of open field activity in the OFT. OB ameliorated the CUMS induced depressive status. OB significantly reduced the corticosterone level and up-regulated protein and gene expressions of BDNF and GR. OB reduced CUMS induced hippocampal neuron atrophy and apoptosis, and increased the number of the astrocytes and new nerve cells. OB significantly increased GFAP-positive cells as well as BDNF and GR immunoexpression in the hippocampus.     

An animal model of a behavioral intervention for depression

Although conditioned inhibition of fear (or learned safety) is a learning process critical for preventing chronic stress, a predisposing factor for depression and other psychopathologies, little is known about its functional purposes or molecular mechanisms. To obtain better insight into learned safety, we investigated its behavioral and molecular characteristics and found that it acts as a behavioral antidepressant in two animal models. Learned safety promotes the survival of newborn cells in the dentate gyrus of the hippocampus, while its antidepressant effect is abolished in mice with ablated hippocampal neurogenesis. Learned safety also increases the expression of BDNF in the hippocampus and leads to downregulation of genes involved in the dopaminergic and neuropeptidergic but not the serotonergic system in the basolateral amygdala. These data suggest that learned safety is an animal model of a behavioral antidepressant that shares some neuronal hallmarks of pharmacological antidepressants but is mediated by different molecular pathways.     

Alternative animal behavior: a model and its statistical characteristics

The rats' alternative behaviour in T-maze at simultaneous two-sided food refreshment in 13 trials a day during 6 days has been studied. It has been found that in the first testing days the indexes of alternative behaviour of animals correspond to the characteristics of the random alternation. However, on the 5-6th day of testing in the overwhelming majority of rats the true deviation of alternation index above or below than the theoretical values has been revealed. A question on the existence of two strategies of cognitive behaviour alteration and perseveration in rat population is under discussion.     

The role of Toxoplasma gondii persistence in human clinical pathology

The publications, including those of the author, on persistence phenomenon of the obligatory intracellular parasite, Toxoplasma gondii, are updated. The latent form of toxoplasmosis was shown to be prevailing. The role of congenital and acquired toxoplasmosis in kids' and adults' pathology, the opportunistic nature of this infection, the reactivating factors of latent and chronic infection as well as the mechanism of pathogen persistence are under discussion.     

Catatonia or depression: the GC rat strain as an animal model of psychopathology

The utility of "incomplete" genetic animal models of human diseases, in particular, psychoses, is discussed. The GC rat strain selected for predisposition to cataleptic reactions is described. It is shown that in many of their characteristics, GC rats are similar to schizophrenic and depressive patients. A possibility that akinetic catatonic states and depressions, hyperkinetic catatonic states and mania share common mechanisms is discussed. It is hypothesized that the GC strain may be an incomplete model of the common genetic and pathogenetic core of schizophrenic substuporous states and depression, which suggests the importance of returning to the issue of a unitary psychosis (Einheitpsychosis).     

In vitro neurotransmitter release in an animal model of depression.

Sprague-Dawley rats exposed to uncontrollable shock can be separated by a subsequent shock escape test into two groups: a "helpless" (LH) group which demonstrates a deficit in escape behavior, and a "nonlearned helpless" (NLH) group which shows no escape deficit and acquires the escape response as readily as naive control rats (NC) do. The present studies were designed to examine the correlations between the behavioral differences and the changes of in vitro neurotransmitter release seen in these three groups of rats. The major finding concerned a significant increase in endogenous and K(+)-stimulated serotonin (5-HT) release in the hippocampal slices of LH rats. There were no apparent differences in acetylcholine, dopamine and noradrenaline release in the hippocampus of LH rats as compared to NLH and NC rats. These results add further support to previous studies in our laboratory which implicate presynaptic 5-HT mechanisms in the behavioral deficit caused by uncontrollable shock.     

Netherlands twin family study of anxious depression (NETSAD).

In a longitudinal study of Dutch adolescent and young adult twins, their parents and their siblings, questionnaire data were collected on depression, anxiety and correlated personality traits, such as neuroticism. Data were collected by mailed surveys in 1991, 1993, 1995 and 1997. A total of 13,717 individuals from 3344 families were included in the study. To localise quantitative trait loci (QTLs) involved in anxiety and depression, the survey data were used to select the most informative families for a genome-wide search. For each individual a genetic factor score was computed, based on a genetic multivariate analysis of anxiety, depression, neuroticism and somatic anxiety. A family was selected if at least two siblings (or DZ twins) had extreme factor scores. Both discordant (high-low) and concordant (high-high and low-low) pairs were included in the selected sample. Once an extreme sibling pair was selected, all family members (parents and additional siblings of the selected pair) who had at least once returned a questionnaire booklet were asked to provide a DNA sample. In total, 2724 individuals from 563 families (1007 parents and 1717 offspring) were approached and 1975 individuals from 479 families (643 patients and 1332 offspring) complied by returning a buccal swab for DNA isolation. All offspring from selected families were asked to participate in a psychiatric interview and in a 24-hour ambulatory assessment of cardiovascular parameters and cortisol. The interview consisted of the WHO-Composite International Diagnostic Interview and was administered to 1253 offspring. In this paper we describe the genetic-epidemiological analyses of the survey data on anxiety, somatic anxiety, neuroticism and depression. We detail how these data were used to select families for the QTL study and discuss strategies that may help elucidate the molecular pathways leading from genes to anxious depression.     

Effects of reinforcer magnitude on an animal model of impulsive behavior

The effects of altering sucrose solution concentration on discounting of delayed rewards in rats were examined. Five different delays were used (0, 1, 2, 4, and 8s) and three different sucrose solution concentrations (3, 10, and 30%). It was hypothesized that high value sucrose solution concentrations would be discounted less than low value sucrose solution concentrations. The results indicated that the rats discounted the 30% sucrose solution concentration at a higher rate than the 3 or 10% sucrose solution concentration, a finding that apparently contradicted the hypothesis that higher value sucrose solution concentrations would be discounted less than lower value sucrose solution concentrations. However, a follow up experiment indicated that the 3 and 10% sucrose solution concentrations were preferred over the 30% concentration. Thus the results of Experiment 1 can be interpreted as supporting the hypothesis that high valued sucrose solution concentrations are discounted less than lower valued sucrose solution concentrations.     

Dither: A unifying model of the effects of visitor numbers on zoo animal behavior

Interest in the impact of human presence on the behavior and well-being of zoo and aquarium animals is increasing. Previous work has conceptualized the presence of zoo visitors as having one of three impacts on the behavior of animals in zoos: positive, negative, or neutral. Research suggests the same species may exhibit all three responses under different conditions, calling into question whether the positive/negative/neutral framework is the most useful way of considering visitor impact on animal behavior. Here we present a model of visitor effects that unifies these three predictions. Our model suggests that zoo-goers may provide a “dither effect” for some animals living in zoos. We posit animals may show nonlinear behavioral responses over a range of visitor densities, effectively exhibiting changes in both comfortable and anxiety-like behaviors under different levels of human presence. We tested this model during two COVID-19 related closures at the San Francisco Zoo, studying seven species for evidence of nonlinear relationships between visitor numbers and animal behavior. Our results support the dither effect acting in several species observed.     

Virus persistence in an animal model of multiple sclerosis requires virion attachment to sialic acid coreceptors

Persistent Theiler's virus infection in the central nervous system (CNS) of mice provides a highly relevant animal model for multiple sclerosis. The low-neurovirulence DA strain uses sialic acid as a coreceptor for cell binding before establishing infection. During adaptation of DA virus to growth in sialic acid-deficient cells, three amino acid substitutions (G1100D, T1081I, and T3182A) in the capsid arose, and the virus no longer used sialic acid as a coreceptor. The adapted virus retained acute CNS virulence, but its persistence in the CNS, white matter inflammation, and demyelination were largely abrogated. Infection of murine macrophage but not oligodendrocyte cultures with the adapted virus was also significantly reduced. Substitution of G1100D in an infectious DA virus cDNA clone demonstrated a major role for this mutation in loss of sialic acid binding and CNS persistence. These data indicate a direct role for sialic acid binding in Theiler's murine encephalomyelitis virus persistence and chronic demyelinating disease.     

以田鼠作为动物模型来研究社会行为的进化:基因、脑与行为

田鼠属的一些近缘种间具有独特的社会行为多态性。例如Microtusochrogaster和M .pinetorum为一夫一妻制 ,而M .montanus和M .pennsylvanicus则为独居和一夫多妻制。无论是在野外还是人工饲养的条件下 ,单配制的田鼠其雌、雄成年个体一经交配即在两者之间形成长期的配偶关系并且双亲共同哺育后代。已证明神经多肽加压素 (Vasopressin)参与了田鼠单配制行为的神经调控。本篇综述了过去以及近期关于加压素调控田鼠配偶关系形成的研究结果和进展。首先 ,阐述了加压素V1a受体 (V1aR)在脑分布的种间差异 ,并以此来鉴别特定脑区在配偶关系形成中的功能 ;其次 ,探讨了运用V1aR拮抗物的药理学方法来决定究竟哪些脑区参与配偶关系的形成 ,还描述了田鼠种间V1aR基因结构和功能的不同 ,以及这些不同对V1aR在大脑的分布和行为调控潜在的作用机制 ;最后 ,讨论了最新的研究结果 ,即对一夫多妻制田鼠进行脑V1aR基因的改造 ,从而使之表现出一夫一妻制田鼠的行为。总之 ,了解复杂的社会性行为的遗传和神经机制可以加深我们对种间和种内行为分歧进化的理解     

Contribution of pathology to laboratory animal welfare

To promote experimental animal welfare, several countries are engaged in establishing local animal research review committees and appointing supervising veterinarians or other experts. However, a number of adverse conditions leading to intercurrent illness or death remains unnoticed or unidentified. Pathological investigation of unexpectedly ill or dead animals proved to be very useful in indicating conditions compromising animal welfare. In addition, such post-mortem findings may be instructive, with respect to welfare, for those involved in experiments with animals.