6 days ago CO-APPLICANTS. Only a single Exploratory Pre-Seed Grant is permitted for activities Research activities, including bench fee1. CO-APPLICANTS. Only a single Exploratory Pre-Seed Grant is permitted for activities related to commercialization related activities. Table |CR Effects on Rat Behavior FREQ | BDC |ON | RATIO &|Lyskov et al () aggressiveness Mg” Enhanced exploratory activity in rats.
Exploratory activity 2.4.4
Behavior of the controls, Win21 and Los21 in the elevated plus- maze test. Behavioral parameters Control Win21 Los Total entries, N Head- dips, N Additionally, the LSD test revealed differences between the controls and Los21 in open - arm entries.
T he post hoc. Bonferroni test rev ealed significant dif ferences Figure 4 in the following comparisons: Thus, the number of crossed squares and number of rearings were increased and the number. Be havioral o b-. No differences in the la-. On the followi ng days, there were n o inversions of. Eve ry day, the winners demonstrated aggres sion during all exp erimental. The scores e stimating the aggre ssiveness in male m ice — th e total time and number of attacks and the. On the one hand, the decrease i n aggressiveness sco res could be a conseque nc e of.
Thereafter, the behavior of the losers. As a result, the acti ve forms of offensi ve aggression were pa rtly replaced by ag gressive grooming a nd indirect. How ever, as our results show d uring agonistic int eractions, the. Behavior of Los21 after 21 days of agonistic interactions in the Porso lt t est.
Immobility time indicating a d epre s-. Most of time during the test they d emo n-. On the other hand, an increased num ber of jumps and rot ations indicated the deve l-.
The significant ne gative correlation f ound between the tot al time of attacks and the sum of. Similarly with Win21, Win10 demonstrated strong. Overactive behaviors such as abnormal explo ratory behavior and locom otor. The num ber of crossed. Sim ilar to earlier data on m ice of other strain s.
This means that the partition test could serve as a tool for measuring the expression of aggression moti vation. Thus, in the winners, repeated experiences of aggression led to the. Most of these changes ma nifest ed themselves. The expressed behavioral changes were observed in the losers with a repeated experience of social defeats.
In t he plus - maze immediately after the start of the test, the losers spent. Later the mice began to explore the ope n arms. Pronounced a nxi ety was found in the losers as estimated. The controls explored both the c losed and o pen. The total tim e spent near the parti tion as a reaction t o a partner in the neighboring compart ment in a.
Thus, bo th tests indicate d an increased anxiety - like state in the d e-. Surprisingly, the CD - 1 losers displayed loco motor hyperactivity i. A decr ease in self - gro oming behavior in. The Porsolt tes t revealed an increased time o f i m-.
Thus, CSDS seemed to lea d to the development of pronounced anxiety, de pression, and locomot or and explor a-. The analysis of behavioral changes in mice with alternative social behaviors i n-. Previously, in a similar battery of tests, we studied the effects of chronic agonistic interaction s on the behavior. After three weeks of intermale confro n-. Earlier on, after E. Hyperactivity scores from the open - field test, estimated as the number of crossed squares, were similar in the.
A fter a prolonged e xperience of aggressi on, all winners dem onstra ted stereotyped l ocomotor. The development of depressiveness in the Porsolt test was observed in. The CD - 1 losers demonstrated a unique com bination of hyperact ivity —.
Hyperactivity is a sym ptom of bipolar disorder , which is characterize d by alternate episodes of depression and. Mania periods are characterized primarily by overactive behavior  manifested as a variety of. Such symptoms include overa c-.
In a nimal models for bipolar disorder  -  , a mania - like state can be induced. Additionally, genetically modified animals including mice with targeted mutations of the glutamate receptors,. Clock gene, dopamine transporter, or trans genic mice were used for the modeling of t he mania - like state  ,.
The MNS mice derived via multiple rounds of. We believe that outbre d CD - 1 mice that demonstrated, under repeated experiences of aggression and defeat,. The unique beha vioral changes observe d in the losers and wi nners might also be us eful. Mo reover, when com paring the effects of repeated social ex perience of aggressi on and defeats. This work wa s supported by Russian. Pharmacology , Biochemistry and Behavior , 38 , Aggressive Behavior , 24 , Science , , Cell , , Behavioral Brain Research , , Pharmacology , Biochem i-.
Zhurnal of Visshej Nervnoj. Deyatelnosty , 53 , Like State in Mice. Behavioural Processes , 20 , Nature Protocols , 6 , Genetics , 37 , Spontaneous Diseases in Commonly Used Mouse. Animals , 30 , Journal of the National Cancer Institute , 55 , Toxicologic Pathology , 21 , Pathology , 16 , Reflections from Toxicity Stu-.
Laboratory Animals , 47 , Behavioral Brain Resear ch , , Neuroscience and Biobehavioral Reviews , 23 , Aggressive Behavior , 17 , Nature Protocols , 9 , Psychopharmacology , 92 , Nature , , The Psychopathology of Repeated Aggression: Anxiety in Male Mice.
Behavioural Brain Research , , Zhurnal of Vysshej Nervnoj Deyatelnosti , 63 , Physiology and Behavior , 61 , Toward a Neurops ychological Model. Sp ielberger , C. Zhurnal of Vysshej Nervnoj Deyatelnosti. Update on the Treatment of Acute Mania. The World Journal of Biological Psychiatry , 10 , Hits, Misses and Future Dire c-.
British Journal of Pharmacology , , Cell Tissue Research , , Disease Models and Mechanisms , 2 , Physiology and B e-. Revista Brasileira de Psiquiatria , 35 , S -S International Journal of Neuropsychopharmacology , 14 , Bipolar Disorders , 14 , Bipolar Disorders , 9 , Frontiers in Psychiatry , 1 , An Animal Model of Mania. Neuropsychopharmacology , 36 , Human Gene for S Beta. Journal of Psychiatry Neuroscience , 20 , Biological Psychiatry , 53 , Molecular Ps ychiatry , 13 , -.
Journal of Affe c-. When aggression does occur, it is not only the losers that experience poor welfare. Male mice experiencing repeated positive fighting outcomes during daily agonistic interactions have been found to develop pronounced aggression, anxiety-like behaviour and impulsivity, disturbances in motivated and cognitive behaviours, and impairments of sociability  .
They also displayed hyperactivity, attention-deficit behaviour, motor dysfunctions and repetitive stereotyped behaviours e. Although it may be assumed that winning would be a positive outcome for the victor, these observations imply detrimental effects of repeated winning, combined with the associated stress of repeated fighting and the pressure of maintaining hierarchical status, collectively resulting in different types of psychopathy such as hyperactivity and depression, key symptoms of bipolar disorder .
To Group or Not to Group? Simple Summary Wild mice live in territories inhabited by one adult male, several females, and their offspring. This cannot be replicated in the laboratory, so male mice are usually housed in single-sex groups or individually. However, there can be serious animal welfare problems associated with both these approaches, such as lack of social contact when housed individually or aggression between males when kept in groups.
All of this can also affect the quality of the science, giving rise to ethical concerns. This review discusses whether it is in the best welfare interests of male mice to be housed in groups, or alone. We conclude that it is not possible to give general recommendations for good practice for housing male laboratory mice, as responses to single- and group-housing can be highly context-dependent.
The welfare implications of housing protocols should be researched and considered in each case. Even without aggression, not all animals within a group will be in a state of positive welfare. Rather, many male mice may be negatively affected by the stress of repeated social defeat and subordination, raising concerns about welfare and also research validity. However, individual housing may not be an appropriate solution, given the welfare implications associated with no social contact.
An essential question is whether it is in the best welfare interests of male mice to be group- or singly housed. This review explores the likely impacts—positive and negative—of both housing conditions, presents results of a survey of current practice and awareness of mouse behavior, and includes recommendations for good practice and future research. We conclude that whether group- or single-housing is better or less worse in any situation is highly context-dependent according to several factors including strain, age, social position, life experiences, and housing and husbandry protocols.
It is important to recognise this and evaluate what is preferable from animal welfare and ethical perspectives in each case. A new animal model sensitive to antidepressant treatments. It was shown that the long-term experience of aggression led to development of hyperactivity estimated as increased motor activity in different tests: Symptoms of attention deficit estimated in the "partition" test as a reduction of the communicativeness and the lack of reaction to unfamiliar partner were noticed.
Appearance of a large number of hyperkinesis manifested most often in the form of sudden involuntary head movements jerks was observed in the behavior of aggressive males during agonistic interactions. Similarity of symptomatics of movement disturbances in mice and in humans with some neurological diseases is discussed.
Repeated positive fighting experience in male inbred mice. Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse.
However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model SCM , widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression.
Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice.
Severe neuropathology develops in male mice after d of agonistic interactions. Contributions of animal models to the study of mood disorders. Mood disorders are a leading cause of morbidity and mortality, yet their underlying pathophysiology remains unclear.
In this scenario, the development of different animal models contributes to our understanding of the neurobiology of these disorders and provides the possibility of preclinical pharmacologic screening. The present review seeks to provide a comprehensive overview of traditional and recent animal models, recapitulating different features and the possible pathologic mechanisms of mood disorders emulated by these models.
Abstract N-methyl-D-aspartate receptor NMDAR -mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stress-related disorders. For predation stress, mice were introduced into transparent containers that were placed in a rat home cage during the night; social defeat was applied during the daytime using aggressive CD1 mice. This treatment impaired hippocampus-dependent performance during contextual fear conditioning.
A correlation between this behaviour and food displacement performance was demonstrated, suggesting that burrowing behavior is affected by the stress procedure and is hippocampus-dependent. Dopamine depletion attenuates some behavioral abnormalities in a hyperdopaminergic mouse model of bipolar disorder.
Behavioral and physiological markers of experimental depression induced by social conflicts DISC. Repeated defeat experiences in daily agonistic confrontations induced dramatic changes in behaviors as well as in the somatic state of submissive mice losers that were similar to symptoms of human depression with respect to etiology, susceptibility to treatment, and symptomatology.
A remarkable behavioral deficit was found in losers, who demonstrated only a passive defense and immobile postures after 20 daily defeats tests instead of active defense and withdrawal, which had predominated in the first confrontations. Losers never demonstrated any aggression to other individuals and displayed a decrease in ambulation in the open-field test as well as an increase in immobility time in Porsolt's test.
The development of anxiety and disturbance in communicative behavior were observed in losers. Loss of weight and enhancement of gastric mucosa damage, as well as a decrease in plasma testosterone level and immune resistance, were shown in losers.
Chronic unavoidable social stress is considered a pathogenic factor, which leads to the development of depressive pathology and anxiety in mice. Ten minutes following infusions, rats were tested in the behavioral battery described below. Previous reports, and pilot data for this project, have demonstrated that infusions to the anterior medial aspect of the VTA are most effective at enhancing lordosis [ 10 ].
Every rat was individually tested through the following battery in the order described below. The testing apparatus were brightly lit from above with three fluorescent bulbs 32 W each. Testing occurred in a single room, in a sequential manner, with no breaks between individual tasks other than time needed to clean apparatus and move rats from one task to the next.
It took approximately 45—50 min for each rat to be tested through the battery described below. Behavior in the open field is used as a measure of exploration, anxiety, and locomotor behavior [ 14 , 36 ]. Per previous methods, rats were placed in the open field and the path of their exploration was recorded for 5 min.
The number of central, peripheral, and total entries was then calculated from these data as indices of anti-anxiety, thigmotaxis, and motor behavior, respectively. Behavior in the elevated plus maze is also utilized to assess exploration, anxiety, and motor behavior [ 14 , 37 ].
The elevated plus maze consists of four arms, 49 cm long and 10 cm wide, elevated 50 cm off the ground. Two arms were enclosed by walls 30 cm high and the other two arms were exposed. As per previous methods, rats were placed at the juncture of the open and closed arms and the number of entries into, and the amount of time spent on, the open and closed arms were recorded during a 5-min test. Time spent on the open arms is an index of anxiety and the total number of arm entries is measure of motor activity.
A modified version of the previously established partner preference task was utilized to assess preference for an intact male or a conspecific [ 14 , 38 ]. Stimulus rats were enclosed in Plexiglass compartments with small holes 1 cm diameter drilled in the bottom portion of the enclosure exposed to the center of the open field, so that experimental rats could receive visual and olfactory stimulation from stimulus rats in the absence of physical contact.
The amount of time that experimental rats spent within a body's length of stimulus animals was recorded in a 5-min test. Increased time spent in close proximity to one stimulus rat versus another is an indication of a preference for that animal. The social interaction task was used to assess exploratory and anxiety behavior associated with interacting with a novel conspecific [ 14 , 39 ].
The total duration of time that experimental rats engaged an ovariectomized stimulus rat in crawling over and under partner, sniffing of partner, following with contact, genital investigation of partner, tumbling, boxing and grooming was recorded during a 5-min test [ 14 ].
An ovariectomized rat was utilized as the stimulus animal in order to avoid exposure of experimental rats to vaginocervical stimulation, which might occur if a male had been used as the stimulus animal. Duration of time spent interacting with a conspecific is an index of anxiety behavior. Paced mating was utilized over standard mating because of its greater ethological relevance and procedures were carried out as previously reported [ 40 - 43 ]. Paced mating tests were conducted in a chamber Females were placed in the side of the chamber opposite the stimulus male.
Rats were behaviorally tested for an entire ejaculatory series. Behaviors recorded were the frequency of mounts and intromissions that preceded an ejaculation. The percentage of proceptive i. Serum was thawed on ice and steroids extracted as described below. Brains were thawed and midbrain, hippocampus, diencephalon, and cortex were dissected out for all experiments.
For Experiments 2 and 3, remaining subcortical tissue interbrain was also measured as an additional control. As endocrine analyses precluded histological site analyses, brains were visually inspected during dissection to determine infusion site. Notably, endocrine and behavioral data of these rats was different than that of other rats in this group and was omitted from the statistical analyses. Following dissection, steroids were extracted from midbrain, hippocampus, diencephalon, cortex, and interbrain as described below.
Steroid levels in these regions were investigated because they are involved in the mediation of exploration, anxiety, social, and sex behaviors midbrain, hippocampus, diencephalon, and cortex or as control sites interbrain [ 3 , 45 ]. After snap-freezing twice, test tubes containing steroid and ether were evaporated to dryness in a Savant.
Dried down tubes were reconstituted with phosphate assay buffer to the original serum volume. Solvents were removed using a speed drier. Standards were added to assay buffer followed by addition of the appropriate antibody described below and 3 H steroid. The E 2 antibody E , Dr. The P 4 antibody P from Dr. Niswender, Colorado State University , used in a 1: Separation of bound and free steroid was accomplished by the rapid addition of dextran-coated charcoal.
Sample tube concentrations were calculated using the logit—log method of Rodbard and Hutt [ 49 ], interpolation of the standards, and correction for recovery with Assay Zap. The inter- and intra-assay reliability coefficients were: Two-way analyses of variance ANOVA were utilized to examine effects of hormonal milieu estrous cycle phase, fusion condition on endocrine and behavioral endpoints.
Correlational analyses were used to determine the contribution of steroid levels in brain areas examined on performance in individual tasks.
Power analyses were utilized to verify that all inferential statistics reported were valid with sufficient power. Expected estrous cycle variations were observed in all experiments. As previously reported, proestrous, compared to diestrous, rats had significantly higher E 2 and P 4 concentrations in all tissues examined. Neither E 2 nor P 4 levels in midbrain, hippocampus, diencephalon, or cortex correlated with behaviors examined.
Neither estrous cycle phase, nor VTA infusions, influenced the total number of squares entered in the open field Table 3. Neither estrous cycle, nor VTA infusions, influenced total arm entries Table 3.
When given a choice, time spent in close proximity to a stimulus female was also influenced by estrous cycle and VTA infusion. As expected, diestrous rats that received vehicle infusions chose proximity to a female, rather than a male Table 3.
The estrous cycle-dependent differences in endocrine and behavioral measures we observed were congruent with previous reports. Proestrous, compared to diestrous, rats had higher levels of E 2 and progestins in serum, midbrain, hippocampus, diencephalon, and cortex, which were commensurate with previous reports that examined endocrine parameters across the estrous cycle [ 33 , 50 ].
In the present study, proestrous rats engaged in more exploratory, anxiolytic, social, and sexual behavior than did diestrous rats, which is consistent with prior reports that separately investigated changes in these behavioral processes across the estrous cycle [ 14 , 16 , 51 , 52 ].
The present experiment uniquely demonstrates contemporaneous changes in exploratory, anxiolytic, and social behaviors with reproductive behaviors. These data imply that similar endocrine effects may underlie these variations in behaviors and that exploration, anxiolysis, and social behaviors may be functionally linked to reproductive processes. Results of the present study also extend previous findings on estrous cyclicity.
For example, lordosis can be elicited on every day of the estrous cycle, even when E 2 and progestin levels are low [ 53 , 54 ]. Congruent with this, there were low levels of lordosis among diestrous rats infused with vehicle.
These data suggest that low levels of E 2 are a sufficient background milieu for progestins' facilitatory effects on lordosis and other socio-sexual behaviors. This gives rise to increases in dopaminergic signaling and downstream signal transduction processes, in the VTA and its connecting regions striatum, cortex, and hippocampus. These are intriguing data suggesting that progestins modulate behaviors with important ethological relevance in regard to successful mating, as well as other behaviors [ 26 , 72 , 73 ].
The technical assistance of Jason Paris and John Roberts is greatly appreciated. National Center for Biotechnology Information , U. Author manuscript; available in PMC Feb Author information Copyright and License information Disclaimer. The publisher's final edited version of this article is available at Behav Brain Res. See other articles in PMC that cite the published article.
Surgery All rats were stereotaxically implanted with bilateral guide cannulae aimed at the medial aspect of the VTA from bregma: Endogenous Vaginal epithelium was examined daily between 7: Open in a separate window. Behavioral testing Every rat was individually tested through the following battery in the order described below.
Open field Behavior in the open field is used as a measure of exploration, anxiety, and locomotor behavior [ 14 , 36 ]. Elevated plus maze Behavior in the elevated plus maze is also utilized to assess exploration, anxiety, and motor behavior [ 14 , 37 ].
Partner preference A modified version of the previously established partner preference task was utilized to assess preference for an intact male or a conspecific [ 14 , 38 ]. Social interaction The social interaction task was used to assess exploratory and anxiety behavior associated with interacting with a novel conspecific [ 14 , 39 ].
Paced mating Paced mating was utilized over standard mating because of its greater ethological relevance and procedures were carried out as previously reported [ 40 - 43 ]. Tissue preparation Serum was thawed on ice and steroids extracted as described below. Antibodies The E 2 antibody E , Dr. Termination of binding Separation of bound and free steroid was accomplished by the rapid addition of dextran-coated charcoal. Statistical analyses Two-way analyses of variance ANOVA were utilized to examine effects of hormonal milieu estrous cycle phase, fusion condition on endocrine and behavioral endpoints.
Results Expected estrous cycle variations were observed in all experiments. Progesterone in the ventromedial hypothalamus of ovariectomized, estrogen-primed rats inhibits subsequent facilitation of estrous behavior by systemic progesterone. A contributory role for midbrain progesterone in the facilitation of female sexual behavior in rats.
There was a problem providing the content you requested
normal Exploratory Activity Developing in CD-1 Male Mice under .. Open- Field Test. The open-field test  was carried out in a 9 × 9. Hyperactivity and Abnormal Exploratory Activity Developing in CD-1 Male Mice under . Open-Field Test. The open-field test  was carried out in a 9 × 9 . 5 Underground Tests to be Performed in the Exploratory Shaft Facility SCP Section Lead SCP Activity Geologic mapping of the exploratory shaft and drifts Radial borehole tests in the exploratory shaft facility USGS 26 .