Submissive Rats Research Articles

Neuroethological analysis of the features of aggressive and submissive behavior of rats with alcohol dependence during the action of intranasally administered progesterone

The aim of the work was to study in a chronic experiment the effect of intranasal progesterone administration on the specifics of behavioral (aggressive and submissive) reactions of rats with alcohol dependence during agonistic encounters. It was shown that the intranasal administration of progesterone to aggressive rats with alcohol dependence under conditions of long-term psychoemotional consequences of zoosocial confrontational interactions led to a decrease in aggressive motivational reactions (the number and total time of attacks); rats with a subordinate type of behavior with alcohol addiction — to a decrease in quantitative and time indicators of passive-defensive behavior. The features of the anxiolytic and hypnotic effects of progesterone on the emotional behavior of aggressive and submissive rats with alcohol dependence were revealed. Key words: alcohol dependence, intranasal administration of progesterone, agonistic collisions

Social stress causes depressive-like behaviour in submissive rats

Social stress causes depressive-like behaviour in submissive rats

Multimodal cues displayed by submissive rats promote prosocial choices by dominants

Animals often display prosocial behaviors, performing actions that benefit others. Although prosociality is essential for social bonding and cooperation, we still know little about how animals integrate behavioral cues from those in need to make decisions that increase their well-being. To address this question, we used a two-choice task where rats can provide rewards to a conspecific in the absence of self-benefit and investigated which conditions promote prosociality by manipulating the social context of the interacting animals. Although sex or degree of familiarity did not affect prosocial choices in rats, social hierarchy revealed to be a potent modulator, with dominant decision-makers showing faster emergence and higher levels of prosocial choices toward their submissive cage mates. Leveraging quantitative analysis of multimodal social dynamics prior to choice, we identified that pairs with dominant decision-makers exhibited more proximal interactions. Interestingly, these closer interactions were driven by submissive animals that modulated their position and movement following their dominants and whose 50-kHz vocalization rate correlated with dominants' prosociality. Moreover, Granger causality revealed stronger bidirectional influences in pairs with dominant focals and submissive recipients, indicating increased behavioral coordination. Finally, multivariate analysis highlighted body language as the main information dominants use on a trial-by-trial basis to learn that their actions have effects on others. Our results provide a refined understanding of the behavioral dynamics that rats use for action-selection upon perception of socially relevant cues and navigate social decision-making.

Interrelation between Anxiety Level and Aggressiveness

High anxiety is the base not only for depression development but also to impulsive aggression manifestation. In the previous study we revealed the differences in neurohumoral status in animals with submissive and dominant behavioral types. Hypothalamic pituitary adrenal axis hyperactivity, the increase in noradrenaline and the decrease in serotonin levels in limbicocortical regions were observed in submissive male rats (high anxiety). Due to these results, we studied the interrelation between anxiety level and aggressiveness index and its components. The research involved 138 participants: 121 young men aged 18 to 22 years and 17 male adolescents within the age range 15-16 years. They were asked to answer Buss-Durkee Hostility Inventory, Spielberger State-Trait Anxiety Inventory and Eysenck Personality Inventory. The anxiety level was assessed in points. The aggressiveness index, physical, verbal and indirect aggressions were estimated in a percentage of the maximum level. No correlation between the anxiety level and the aggressiveness index was found in whole group of young men. Whole group was separated into three subgroups depending on anxiety level: with high, moderate and low anxiety levels. Strong positive correlation between anxiety level and aggression index in men with high anxiety level and negative correlation between these two parameters in men with low anxiety level were revealed. In last subgroup the correlation was statistically insignificant. In men with moderate anxiety level no correlation between anxiety level and aggression index was observed. This interrelation may be taken into account in anxiety treatment and in the prevention of impulsive aggression manifestation. In whole group of male adolescents no correlation between anxiety and aggressiveness index was found. Obtained data indicate the necessity of participants division depending on anxiety level and using the closed age groups to study the mechanisms of aggression development.

Simultaneous Changes in Sleep, qEEG, Physiology, Behaviour and Neurochemistry in Rats Exposed to Repeated Social Defeat Stress

Depression is a heterogeneous disorder characterized by alterations at psychological, behavioural, physiological, neurophysiological, and neurochemical levels. Social stress is a prevalent stress in man, and the repeated social defeat stress model in rats has been proposed as being the rodent equivalent to loss of control, which in subordinate animals produces alterations that resemble several of the cardinal symptoms found in depressed patients. Here, rats followed a resident-intruder protocol for 4 consecutive days during which behavioural, physiological, and electroencephalographic (EEG) parameters were simultaneously monitored in subordinate rats. On day 5, prefrontal dopamine (DA) and hippocampal serotonin (5-HT) as well as corticosterone were measured in submissive rats that had visual, acoustic, and olfactory (but no physical) contact with a dominant, resident conspecific rat. Socially defeated rats demonstrated increases in ultrasonic vocalizations (20-25 KHz), freezing, submissive defensive behaviour, inactivity, and haemodynamic response, while decreases were found in repetitive grooming behaviour and body weight. Additionally, alterations in the sleep-wake architecture were associated with reduced active waking, enhanced light sleep, and increased frequency of transitions from light sleep to quiet wakefulness, indicating sleep instability. Moreover, the attenuation of EEG power over the frequency range of 4.2-30 Hz, associated with a sharp transient increase in delta oscillations, appeared to reflect increased brain activity and metabolism in subordinate animals. These EEG changes were synchronous with a marked increase in body temperature and a decrease in locomotor activity. Furthermore, psychosocial stress consistently increased 5-HT, DA, and corticosterone levels. The increased levels of cortical DA and hippocampal 5-HT during social threat may reflect a coping mechanism to promote alertness and psychological adaptation to provocative and threatening stimuli. These neurophysiological changes are hypothesized to be the consequence of dynamics in monoamine systems, which could be useful markers for disease progression in the aetiology of depression.

Вміст тестостерону у плазмі крові та серотоніну в мозку агресивних і субмісивних щурів різних вікових груп

Correlation between the level of testosterone in blood plasma and serotonin content in hippocampus and frontal cortex was investigated in aggressive and submissive rats of different age groups. Dependence of the testosterone level on behavior type was found. The highest testosterone level was observed in aggressive animals. In submissive males we found considerable decrease of the serotonin level in frontal cortex and hippocampus as compared with balanced and aggressive ones. The positive correlation between testosterone and serotonin levels was shown in submissive and aggressive animals in contrast to the negative correlation in balanced males. The change in negative correlation between the testosterone and serotonin content into positive one in the aggregate with the decrease or the increase oftestosterone level is likely to be one of the components in formation of submissive and aggressive (dominant) behavior type, respectively.

Blood Plasma Testosterone and Brain Serotonin Levels in Aggressive and Submissive Rats of Different Age Groups

Blood Plasma Testosterone and Brain Serotonin Levels in Aggressive and Submissive Rats of Different Age Groups

Дослідження вмісту тестостерону та тиреоїдних гормонів у плазмі крові щурів із субмісивним та агресивним типами поведінки

The levels of testosterone and thyroid hormones have been investigated in male rats with aggressive and submissive behaviors. An increase of testosterone in aggressive rats and the decrease of that in submissive ones were found when compared with the steady males. No change in the thyroxin level was detected. The level of T3 was not changed in males with aggressive behavior, but it was decreased in submissive rats.

Social status modulates basal IL-1 concentrations in the hypothalamus of pair-housed rats and influences certain features of stress reactivity

Recent findings from our laboratory and others indicate that exposure to stress can increase expression of the pro-inflammatory cytokine interleukin-1 (IL-1). In a series of studies examining this response, we observed pronounced differences in baseline levels of hypothalamic IL-1 of pair-housed rats. We hypothesized that these pair-wise differences might be a result of prolonged social stress associated with dominance/submissiveness, and that the submissive animal would show heightened baseline levels of IL-1. In order to test this hypothesis, we utilized a food competition paradigm (access to cheerios) to assess dominance within a dyad prior to the assessment of hypothalamic IL-1 levels. Based on the results of this test, clear dominance hierarchies were observed in ∼50% of the dyads, a ratio comparable to what has been reported previously. More importantly, this dominant/submissive categorization could be used to predict pair-wise differences in hypothalamic IL-1 with greater than 90% accuracy. Specifically, the submissive rat in each dyad (determined a priori) consistently evinced hypothalamic IL-1 levels that were nearly double that of its dominant cage mate. Further studies demonstrated that submissive rats showed a more rapid and pronounced hyperthermic response to novel environment stress relative to dominant rats. Interestingly, social status had no effect on corticosterone reactivity, even when the nature and intensity of the stressor was varied. Finally, maintenance of a clear dominance hierarchy obfuscated hypothalamic IL-1 responses to footshock exposure, with the most robust increases in hypothalamic IL-1 provoked by footshock being observed in pairs where there was no clear dominance hierarchy. Together, these findings suggest that social status can have a significant impact on stress reactivity and neuroimmune consequences of stressor exposure even in the unperturbed home cage environment.

Different levels of γ‐synuclein mRNA in the cerebral cortex of dominant, neutral and submissive rats selected in the competition test

Synucleins are small proteins regulating the filamentous network that in turn influences the release of dopamine and glutamate neurotransmitters involved in mood and motivation processes. We have studied the pattern of synuclein expression in animal models for mania and depression. Dominant behavior, as defined in a food competition test with dyads of rats, can serve as a model of mania and submissive behavior as a model of depression. The expression of alpha-, beta- and gamma-synuclein was analyzed in four regions of cortex from dominant, neutral and submissive rats using TaqMan reverse transcription-polymerase chain reaction technology. The expression levels of gamma-synuclein were elevated consistently in all regions of cerebral cortex of dominant rats (P <0.05; 23.5 +/- 1.1, normalized units) in contrast to the submissive rat group (10.3 +/- 1.2). Neutral rats had intermediate cerebral cortex levels of gamma-synuclein expression (15.7 +/- 1.4) that were significantly lower than that in dominant rats (P <0.05). No changes in alpha- or beta-synuclein expression were observed among the groups. These studies indicate that gamma-synuclein levels in the cerebral cortex were differentially associated with dominant and submissive behavior.

Reduction of Submissive Behavior in Rats: A Test for Antidepressant Drug Activity

Randomly paired rats were food deprived overnight and placed in an apparatus compelling them to compete for a food reward. About half of these pairs developed a dominant-submissive relationship measured as a significant difference in time spent on the feeder by each rat. This relationship developed over a 2-week period and remained stable for at least the next 5 weeks. Treatment of the submissive subjects, for at least 2 weeks, with imipramine, desipramine, or fluoxetine (10 mg/kg) significantly reduced submissive behavior. The effect faded after cessation of treatment with desipramine. Fluoxetine was further tested at 2.5- and 5-mg/kg doses and showed a dose-dependent reduction of submissive behavior. Treatment of submissive rats with the anxiolytic diazepam (1 mg/kg) was ineffective. The prevalence of dominant-submissive relationships and the effect of desipramine and imipramine on submissive behavior were gender independent. The predictive, face, and construct validity of the behavioral test is discussed.

Amitriptyline increases GABA-stimulated [formula omitted] influx by recombinant (α1γ2) GABA A receptors

WSS-1 cells expressing (α1γ2)GABA A receptors show an augmented 36 Cl − response to GABA in the presence of amitriptyline that is increased by flumazenil, unlike augmentation by diazepam which is blocked by flumazenil. This amitriptyline effect is opposite to the inhibition of GABA-stimulated 36 Cl influx manifested in membrane vesicles prepared from drug-naive rats or submissive rats (a model of depression) but is similar to that seen in tissue from amitriptyline-treated rats or dominant rats. The results suggest a novel mechanism of antidepressant drug action having a delayed onset.

Effects of Amitriptyline on GABA-stimulated 36Cl − uptake in relation to a behavioral model of depression

The dominant-submissive relationship established between two rats competing for food is a model of depression and is used here to divide animals into two behaviorally distinct groups. Basal and GABA-stimulated 36Cl − uptake was investigated for both dominant and submissive rats as well as the in vitro effect of the antidepressant amitriptyline (AMI). Because the antidepressant action of AMI only appears after chronic treatment, the effect of chronic injections of AMI on these behavioral and biochemical measures was also studied. Basal 36Cl − uptake is significantly higher for dominant rats than for submissive rats. Increasing concentrations of AMI added to membrane vesicles enhanced 30 μM GABA-stimulated chloride uptake for dominant rats and inhibited it for submissive rats. Chronic treatment of dominant and submissive rats with AMI reversed these in vitro effects. The biochemical data correspond to the changes of the rats behavior in the dominance test after chronic treatment with AMI. However, this correlation is more clear for dominant than for submissive rats. Specific chloride influx was used as a measure of the sensitivity of GABA A receptor to GABA. This revealed different sensitivity states for GABA A receptors in tissues obtained from dominant and submissive rats. It is possible that the distinct conformational states of GABA A receptor are responsible for differences in rats behavior and in vitro effects of AMI before and after in vivo treatment of rats with this antidepressant.

Maternal aggression as a model for acute social stress in the rat: A behavioral-electrocardiographic study

Maternal aggression of lactating rats was used to induce acute social stress in a resident-intruder paradigm. Behavioral and electrocardiographic responses of male intruders were simultaneously recorded. Cardiac electrical activity was measured by means of a telemetry system which ensured preservation of intruders' behavioral repertoire. Behavioral response to maternal attack was evaluated in terms of percent time spent in passive/submissive (p/s) and active/non-submissive (a/ns) patterns. This allowed us to classify the intruders as submissive, non-submissive, and intermediates. During the test, a significant decrease of average R-R interval (R-R) compared to baseline conditions and the occurrence of arrythmias of different nature were found. Ventricular arrhythmias, including premature ventricular beats and ventricular tachycardias, were present in all the intruders while R-R fluctuations and II degree atrioventricular (A-V) blocks only appeared in submissive and intermediate rats. Most ventricular arrhythmias occurred within the upper range of heart rate and were preceded by periods of low R-R variability. These electrocardiographic events were temporally associated with a/ns behavioral patterns and were related to an increased prevalence of sympathetic activity. On the other hand, R-R fluctuations and II degree A-V blocks preceded by high R-R variability were synchronized with p/s behavior and were ascribed to a predominant inhibitory effect of vagal activation which becomes more pronounced as the level of sympathetic activity increases

Effects of stress on defensive aggression and dominance in a water competition test.

Water-deprived rats in a pair competing for a single source of water quickly establish a firm relationship during which one rat drinks consistently more (dominant) than the other (submissive) animal. This relationship is formed during the first competition and is very stable during subsequent tests. Exposure of dominant rats to a severe (18 hrs immobilization), but not a mild (2 hrs immobilization), stressor reduced markedly aggressive behavior and inverted transiently the dominant submissive relationship of the pairs. Exposure of submissive rats to the severe stressor resulted in only minor reductions of aggressive behavior in these animals. Prestress anxiety predicted stress effects in the dominant animals in that high-anxious animals lost more dominant behavior and weight during stress as compared with low-anxious rats. Thus, severe stress can transiently reduce dominant but not submissive behavior during water competition and high-anxious rats are more prone to lose their aggressive behavior.

INTERACTION OF ETHANOL AND STRESS: RESEARCH WITH EXPERIMENTAL ANIMALS—AN UPDATE

Research on the interaction of ethanol (ET) and stress published since 1981 is reviewed. Chronic physical stressors were found to increase the ingestion of ET compared to nonstressed animals. With foodshock, ingestion of ET decreased during the stress session but rose afterwards. The elevation of ET ingestion produced by daily immobilization was long-lasting and was related to individual initial preference for ET. Psychological stressors also increased ingestion of ET. In rat colonies, dominant rats ingested less ET, whereas submissive rats had the highest intake. Factors that modify the ingestion of ET include neonatal experience and REM sleep deprivation. Early weaning increased, while postnatal handling decreased preference for ET. The effect of postnatal handling may be influenced by genetics. Stress, applied during adult life or prenatally, modifies some, but not all, the acute effects of ET. There were marked individual differences in the interaction of ET and stress with respect to ingestion of ET. Conversely, ET may modify stress-induced behavioural and neurochemical changes. This interaction may be stressor specific. Some stressors increase the ET's effects, whereas others may decrease or not affect them. In brain, ET has been shown to lessen the stress-induced decrease in noradrenaline and 5-hydroxytryptamine (serotonin) levels and those in noradrenaline turnover and alpha 1-receptor binding. Stress-induced changes in plasma catecholamines, corticosterone, non-esterified fatty acids and amino acids, and in the decline in adrenal catecholamines are also lessened by pretreatment with ET. Possible mechanisms for the ET-stress interaction are discussed. These include mediation via the GABA-benzodiazepine-ionophore complex, endogenous opioids, the hypothalamo-pituitary-adrenocortical axis and the noradrenergic system.

Stomach acid secretion in submissive and aggressive rats.

These studies were conducted to determine whether aggressive and submissive behavior are related to either an increase or a decrease in gastric secretion. In Experiment 1, intruder rats placed in an established male-female colony and attacked by a dominant alpha male secreted less acid than intruders exposed to nonaggressive males and females. In Experiment 2, intruders exposed to attack and subsequently returned to the encounter site, but protected from physical attack, still demonstrated a gastric hyposecretion. Rats with chronic gastric cannulas in Experiment 3 also revealed an acid inhibition when attacked and later when exposed to, but protected from, attack. Both intruders and attacking males were prepared with gastric cannulas in Experiment 4. Both demonstrated secretory inhibition following attack and attack-protected sessions. The inhibitory effect was greater and more persistent for intruder rats than for aggressive rats. The inhibition occurring during the attack-protected sessions may have been mediated by some conditioning processes. Other associative mechanisms are discussed, and the present results are also compared with those of relevant clinical reports.

Stomach acid secretion in submissive and aggressive rats.

Stomach acid secretion in submissive and aggressive rats.

Effects of morphine withdrawal on food competition hierarchies and fighting behavior in rats.

The effects of chronic morphine administration and morphine withdrawal on competitive and fighting behaviors in rats were studied in a novel paradigm. Fixed-ratio 20 (FR-20) lever-pressing for food presentation was stabilized before placing pairs of rats, matched by response rate and body weight, in the behavioral testing chambers. Initially, overt fighting occurred, but in 60% of the pairs it dissipated within several sessions, accompanied by the development of stable dominant-submissive responding hierarchies. Invariably, the dominant rat in the initial fighting bouts became the dominant responding rat. Chronic morphine administration and subsequent withdrawal in one or both members of the pairs led to disruptions or reversals in the distribution of responding and to small increases in fighting. These effects were seen as early as 12 h after the second dose of morphine and, in some pairs, lasted at least 28 days after morphine was withdrawn. The results from experiments in which only one rat was made dependent show that both the withdrawn dominant rats and the withdrawn submissive rats contributed to the behavioral changes observed in the pairs during withdrawal. Differential food deprivation in pairs not exposed to morphine did not change the dominant-submissive hierarchies. Significant changes in the distribution of FR-20 responding in the paired condition were evident after FR-20 responding in the unpaired condition returned to control rates. It is therefore concluded that change in so-called appetite for food is not an important determinant of the hierarchical changes observed during protracted withdrawal.

Reversal of visual discrimination problem and differential frustration effects in dominant and submissive rats

Two experiments are reported comparing performance in dominant and submissive rats as determined by a food-competition procedure. Ss in Experiment I were either trained to criterion or overtrained before being reversed on a visual discrimination task. Although the two groups did not differ significantly in learning the initial task, the dominant Ss were significantly slower on reversal than the submissives. Experiment II, which utilized a tandem runway, showed that when the reinforcer which maintained the running response was not available in the first goalbox, submissive rats responded with a greater increase in running speed in the second runway than dominant rats. These findings were discussed as reflecting motivational differences between dominant and submissive rats.