Intruder Rat Research Articles

Social stress under binge-like alcohol withdrawal in adolescence: evidence of cannabidiol effect on maladaptive plasticity in rats.

Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses. As socially stressful events pose particular challenges at developmental stages, this research applied the resident-intruder paradigm as a model of social stress, to highlight behavioural neuroendocrine and molecular maladaptive plasticity in rats at withdrawal from binge-like alcohol exposure in adolescence. In search of a rescue agent, cannabidiol (CBD) was selected due to its favourable effects on alcohol- and stress-related harms. Binge-like alcohol exposed intruder rats displayed a compromised defensive behaviour against the resident and a blunted response of the stress system, in addition to indexes of abnormal dopamine (DA)/glutamate plasticity and dysfunctional spine dynamics in the NAc. CBD administration (60 mg/kg) was able to: (1) increase social exploration in the binge-like alcohol exposed intruder rats, at the expenses of freezing time, and in control rats, which received less aggressive attacks from the resident; (2) reduce corticosterone levels independently on alcohol previous exposure; (3) restore DA transmission and (4) facilitate excitatory postsynaptic strength and remodelling. Overall, the maladaptive behavioural and synaptic plasticity promoted by the intersection between binge-like alcohol withdrawal and exposure to adverse social stress can be rescued by a CBD détente effect that results in a successful defensive strategy, supported by a functional endocrine and synaptic plasticity. The current data highlight CBD's relevant therapeutic potential in alcohol- and stress-related harms, and prompt further investigation on its molecular targets.

Effects of saffron aqueous extract on depression in male Wistar rats with chronic social defeat stress

Background: Depression, as a mental disorder, causes many complications in humans. Saffron has been suggested as one of the effective plants in treating various types of depression. The present study aims to assess the effect of the aqueous extract of saffron on depression caused by chronic social defeat stress (CSDS) in rats. Materials and Methods: To induce CSDS, male Wistar intruder rats (Weight= 220-230 g) were put in the cage of male Wistar resident rats (Weight= 280-300 g) for twelve consecutive days (20 min/day). Five minutes before exposure, the intruder rats received either saffron extract (1, 5, and 10 mg/kg) or saline (1 ml/kg). After the exposure, the animals’ weight, desire for the sucrose solution, and locomotor activity were recorded. In addition, at three stages, blood samples were collected from the retro-orbital sinus of animals to evaluate the plasma corticosterone levels. Data were analyzed in SPSS software using Kolmogorov-Smirnov test and repeated measures analysis of variance. Results: Animals in the stress group showed severe weight loss, decreased desire to drink sucrose solution, decreased mobility, and increased plasma corticosterone level (P<0.05). Administration of saffron aqueous extract with different doses improved these symptoms (P<0.01). Conclusion: The aqueous extract of saffron can reduce depression in the animal model of CSDS through reducing corticosterone secretion in response to stres

The effect of Corvitin on the content of bile acids in the liver of rats under conditions of chronic social stress

The article looks at recent research dealing with changes in the bile acid composition of the bile of outbred male rats under chronic social stress (social defeat in daily male confrontations, 14 days) when administered Corvitin (1 mg/kg, intragastrically, 7 days). Chronic social stress was created by daily agonistic interactions between animals. The main fractions of conjugated bile acids – taurocholic, taurohenodeoxycholic and taurodeoxycholic, glycocholic, glycochenodeoxycholic and glycodeoxycholic and free ones – cholic, chenodeoxycholic and deoxycholic were determined by the method of thin layer chromatography of bile. The conjugation index (ratio of the sum of conjugated cholates to the sum of free ones) and hydroxylation (ratio of the sum of trihydroxycholanic bile acids to the sum of dihydroxycholanic ones) of bile acids were calculated. The research showed that in the conditions of experimental social stress, Corvitin enhances the conjugation of bile acids with taurine and glycine, i.e. stimulates detoxification processes in hepatocytes. In the conditions of chronic social stress in male rats, the processes that had provided the flow of glycoconjugates of bile acids from hepatocytes to the bile ducts were further suppressed. The concentrations of glycocholic acid and glycochenodeoxycholic and glycodeoxycholic acids in the bile of male intruders were lower than the control values. But, as seen in the experiment, the use of Corvitin normalized these indicators. The experiment showed that in the conditions of chronic social stress, the content of cholic acid in the bile of intruder rats decreased, and when correcting the pathological condition using Corvitin, it reached the control values. The use of Corvitin simultaneously with the simulation of experimental social stress normalized the biliary secretory function of the liver, indicating the high potential of using Corvitin as a corrective factor in chronic social stress. Correction of stress-induced pathologies of liver bile-secretory function by Corvitin requires further thorough experimental studies.

Repeated victorious and defeat experiences induce similar apical dendritic spine remodeling in CA1 hippocampus of rats

In this study, apical dendritic spine density of neurons in hippocampal, amygdalar and prefrontal cortical areas was compared in rats that were repeatedly winning or losing social conflicts. Territorial male wild-type Groningen (WTG) rats were allowed multiple daily attacks (>20 times) on intruder males in the resident-intruder paradigm. Frequent winning experiences are known to facilitate uncontrolled aggressive behavior reflected in aggressive attacks on anesthetized males which was also observed in the winners in this study. Both winners and losers were socially housed during the experiments; winners with females to stimulate territorial behavior, and losers with two other losing male rats. Twenty-four hours after the last social encounter, brains from experienced residential winners and repeatedly defeated intruder rats were collected and neuronal morphology in selected brain regions was studied via Golgi-Cox staining. Results indicate that spine density in the apical dendrites of the hippocampal CA1 reduced similarly in both winners and losers. In addition, winners showed increased spine densities at the proximal segments (20−30 μm) of the basolateral amygdala neurons and losers tended to show a decreased spine density at the more proximal segments of the infralimbic region of prefrontal cortex neurons. No effect of winning and losing was observed in the medial amygdala. The atrophic effect of repeated defeats in hippocampal and prefrontal regions was anticipated despite the fact that social housing of the repeatedly losing intruder males may have played a protective role. The reduction of hippocampal spine density in the winners seems surprising but supports previous findings in hierarchical dominant males in rat colonies. The dominants showed even greater shrinkage of the apical dendritic arbors of hippocampal CA3 pyramidal neurons compared to the stressed subordinates.

Repeated social defeat promotes persistent inflammatory changes in splenic myeloid cells; decreased expression of \u03b2-arrestin-2 (ARRB2) and increased expression of interleukin-6 (IL-6)

BackgroundPrevious studies suggest that persistent exposure to social stress in mammals may be associated with multiple physiological effects. Here, we examine the effects of social stress in rats, i.e. repeated social defeat, on behavior, hypothalamic–pituitary–adrenal (HPA)-axis and immune system.MethodsA resident-intruder paradigm, where an intruder rat was exposed to social stress by a dominant resident rat for 1 hour each day for 7 consecutive days was used. The day after the last stress exposure in the paradigm the data were analyzed. Variation in social interaction was observed manually, whereas locomotion was analyzed off-line by a purpose-made software. Gene expression in the pituitary gland, adrenal gland and myeloid cells isolated from the spleen was measured by qPCR.ResultsThe exposure to social stress induced decreased weight gain and increased locomotion. An increased nuclear receptor subfamily group C number 1 (NR3C1) expression in the pituitary gland was also shown. In myeloid cells harvested from the spleen, we observed decreased expression of the β2-adrenergic receptor (ADRB2) and β-arrestin-2 (ARRB2), but increased expression of interleukin-6 (IL-6). Subsequent analyses in the same cells showed that ARRB2 was negatively correlated with IL-6 following the stress exposure.ConclusionOur results show that that the experience of social stress in the form of repeated social defeat in rats is a potent stressor that in myeloid cells in the spleen promotes persistent inflammatory changes. Future research is needed to examine whether similar inflammatory changes also can explain the impact of social stress, such as bullying and harassment, among humans.

Activating dopamine D2 receptors reduces brown adipose tissue thermogenesis induced by psychological stress and by activation of the lateral habenula

Emotional hyperthermia is the increase in body temperature that occurs as a response to an animal detecting a salient, survival-relevant stimulus. Brown adipose tissue (BAT) thermogenesis, controlled via its sympathetic innervation, contributes to this temperature increase. Here, we have used an intruder rat experimental model to determine whether quinpirole-mediated activation of dopamine D2 receptors attenuates emotional hyperthermia in conscious rats. In anesthetized rats, we determined whether systemic quinpirole reduces BAT nerve discharge induced by activation of the medullary raphé and the lateral habenula (LHb). We measured BAT and body temperature with chronically implanted thermistors in conscious, freely moving, individually housed, male rats (resident rats). Either vehicle or quinpirole was administered, intraperitoneally, to the resident rat 30 min before introduction of a caged intruder rat. Quinpirole, in a dose-dependent manner, reduced intruder-elicited increases in BAT and body temperature. Pre-treatment with the D2 antagonist spiperone, but not the selective D1 antagonist SCH-23390, prevented this quinpirole-elicited decrease. In anesthetized rats, quinpirole abolished BAT sympathetic nerve discharge elicited by bicuculline-mediated activation of the LHb, but not the medullary raphé. Thus, activation of dopamine D2 receptors reduces the BAT thermogenesis that contributes to emotional hyperthermia. We provide evidence that these dopamine D2 receptors are located in the thermogenic pathway between the LHb and the lower brainstem pre-sympathetic control centre in the medullary raphé.

Stress-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Blockade of Angiotensin-Converting Enzyme or Tumor Necrosis Factor-α.

Post-traumatic stress disorder (PTSD) is characterized by a disordered stress response and associated with increased cardiovascular disease risk. The present study investigated whether angiotensin (Ang) II-elicited hypertensive response is sensitized in a model of PTSD and whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor (TNF)-α prior to PTSD blocks this sensitization of Ang II hypertension. The resident-intruder paradigm was used to model PTSD. Each intruder rat (male Sprague-Dawley) was given normal drinking water or was pretreated with either an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water for 2 weeks. Subsequently, they were exposed to a different resident (male Long-Evans) for 2 hours on 3 days with each session separated by 1 day and then received a subcutaneous infusion of Ang II for 2 weeks. The stressed rats had a significantly enhanced hypertensive response to the Ang II infusion (stressed Δ40.2 ± 3.9 mm Hg vs. unstressed Δ20.5 ± 4.5 mm Hg) and an upregulation of mRNA or protein expression of renin-angiotensin system (RAS) and proinflammatory cytokine (PIC) components and of a microglial marker in the lamina terminalis and hypothalamic paraventricular nucleus when compared with unstressed control rats. Both the sensitized hypertensive response and enhanced gene and protein expression were blocked by pretreatment with either ACE (Δ21.3 ± 3.9 mm Hg) or TNF-α inhibitor (Δ21.4 ± 2.6 mm Hg). The results indicate that upregulation of the brain RAS and PICs produced by severe stress contributes to traumatic-induced sensitization of hypertensive response to Ang II, and disorders such as PTSD may predispose individuals to development of hypertension.

More than reproduction: Central gonadotropin-releasing hormone antagonism decreases maternal aggression in lactating rats.

Gonadotropin-releasing hormone (GnRH) is a major regulator and activator of the hypothalamic-pituitary-gonadal axis. Many studies have demonstrated the importance of GnRH in reproduction and sexual behaviour. However, to date, only a single study shows an involvement of GnRH in maternal behaviour where a 30% reduction of GnRH neurones abolishes a mother's motivation to retrieve pups. On this basis, we aimed to investigate the effects of acute central GnRH receptor blockade in lactating rats on maternal care under non-stress and stress conditions, maternal motivation in the pup retrieval test, maternal anxiety on the elevated plus maze, and maternal aggression in the maternal defence test. We found that acute central infusion of a GnRH antagonist ([d-Phe2,6 ,Pro3 ]-luteinising hormone-releasing hormone; 0.5ng5μL-1 ) impaired a mother's attack behaviour against a female intruder rat during the maternal defence test compared to vehicle controls. However, in contrast to the previous study on reduced GnRH neurones, acute central GnRH antagonism did not affect pup retrieval, nor any other parameter of maternal behaviour or maternal anxiety. Taken together, GnRH receptor activation is mandatory for protection of the offspring. These findings shed new light on GnRH as a neuropeptide acting not exclusively on the reproductive axis but, additionally, on maternal behaviour including pup retrieval and maternal aggression.

Distinct effects of early-life experience and trait aggression on cardiovascular reactivity and recovery

We previously demonstrated independent effects of early-life experience (ELE) and trait aggression (TA) on resting heart rate (HR) and mean arterial pressure (MAP) in rats. The present study examined the effects of TA and ELE on stress-evoked cardiovascular reactivity and recovery. Pups born to Wistar-Kyoto dams were exposed to daily 180-min periods of maternal separation (MS) during the first two weeks of life, and aggression was assessed in adult offspring using the resident-intruder test. Radiotelemetry was then used to record stress-evoked HR and MAP responses in response to: strobe light, novel environment, intruder rat, or restraint. Maximal HR and MAP responses were quantified as indices of reactivity, and exponential decay curves were fitted to determine decay constants as a measure of recovery. Strobe light was the weakest stressor, evoking the lowest increases in MAP and HR, which were significantly greater in MS-exposed rats irrespective of TA. In contrast, reactivity to and recovery from exposure to a novel environment or an intruder were significantly influenced by TA, but not ELE. TA animals exhibited greater reactivity in both of these paradigms, with either decreased (novel environment) or increased (intruder) recovery. Restraint stress induced the largest changes in HR and MAP with the slowest recovery, and these responses were shaped by a significant ELE x TA interaction. These data indicate that cardiovascular reactivity and recovery are influenced by ELE, TA, or ELE x TA interaction depending on stressor aversiveness as well as its physical and psychological dimensions.

Abstract P389: Post-traumatic Stress-induced Sensitization of Angiotensin II Hypertension is Reversed by Blockade of Angiotensin-converting Enzyme or Tumor Necrosis Factor-alpha

Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrated that post-traumatic stress disorder (PTSD) sensitizes angiotensin (ANG) II-elicited hypertension, which was associated with upregulation of central renin-angiotensin system (RAS) components and proinflammatory cytokines (PICs). The present study investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) prior to PTSD blocks sensitization of ANG II-elicited hypertensive response. The resident-intruder paradigm was used to model PTSD. Each intruder rat (male Sprague-Dawley) was pretreated with ACE inhibitor (captopril, 0.5 mg/Ml) or with TNF-α inhibitor (pentoxifylline, PTX, 100 mg/kg/day) in the drinking water for two weeks and then exposed to a different resident (male Long-Evans) for 2 hours on three days with each session separated by 1 day. Beginning 3 days after the last exposure, the intruder (PTSD) rats and unstressed control rats received a subcutaneous infusion of ANG II (120 ng/kg/min) for 2 weeks. The PTSD rats had a significantly enhanced hypertensive response to the ANG II infusion and an upregulation of mRNA expression of RAS and PIC components and of a microglial marker in the lamina terminalis (LT) when compared to control rats. Both the sensitized hypertensive response and enhanced gene expression were blocked by pre-treatment with either ACE inhibitor or TNF-α antagonist. These results suggest that upregulation of the brain RAS and PICs produced by a severe stress contribute to PTSD-induced sensitization of the hypertensive response to ANG II.

Clozapine, chlorpromazine and risperidone dose-dependently reduce emotional hyperthermia, a biological marker of salience

RationaleWe recently introduced a new rat model of emotional hyperthermia in which a salient stimulus activates brown adipose tissue (BAT) thermogenesis and tail artery constriction. Antipsychotic drugs, both classical and second generation, act to reduce excessive assignment of salience to objects and events in the external environment. The close association between salient occurrences and increases in body temperature suggests that antipsychotic drugs may also reduce emotional hyperthermia.ObjectivesWe determined whether chlorpromazine, clozapine, and risperidone dose dependently reduce emotionally elicited increases in BAT thermogenesis, cutaneous vasoconstriction, and body temperature in rats.MethodsRats, chronically instrumented for measurement of BAT and body temperature and tail artery blood flow, singly housed, were confronted with an intruder rat (confined within a small wire-mesh cage) after systemic pre-treatment of the resident rat with vehicle or antipsychotic agent. BAT and body temperatures, tail blood flow, and behavioral activity were continuously measured.ResultsClozapine (30 μg–2 mg/kg), chlorpromazine (0.1–5 mg/kg), and risperidone (6.25 μg–1 mg/kg) robustly and dose-relatedly reduced intruder-elicited BAT thermogenesis and tail artery vasoconstriction, with consequent dose-related reduction in emotional hyperthermia.ConclusionsChlorpromazine, a first-generation antipsychotic, as well as clozapine and risperidone, second-generation agents, dose-dependently reduce emotional hyperthermia. Dopamine D2 receptor antagonist properties of chlorpromazine do not contribute to thermoregulatory effects. Interactions with monoamine receptors are important, and these monoamine receptor interactions may also contribute to the therapeutic effects of all three antipsychotics. Thermoregulatory actions of putative antipsychotic agents may constitute a biological marker of their therapeutic properties.

New insights on amygdala: Basomedial amygdala regulates the physiological response to social novelty

The amygdala has been associated with a variety of functions linked to physiological, behavioral and endocrine responses during emotional situations. This brain region is comprised of multiple sub-nuclei. These sub-nuclei belong to the same structure, but may be involved in different functions, thereby making the study of each sub-nuclei important. Yet, the involvement of the basomedial amygdala (BMA) in the regulation of emotional states has yet to be defined. Therefore, the aim of our study was to investigate the regulatory role of the BMA on the responses evoked during a social novelty model and whether the regulatory role depended on an interaction with the dorsomedial hypothalamus (DMH). Our results showed that the chemical inhibition of the BMA by the microinjection of muscimol (γ-aminobutyric acid (GABAA) agonist) promoted increases in mean arterial pressure (MAP) and heart rate (HR), whereas the chemical inhibition of regions near the BMA did not induce such cardiovascular changes. In contrast, the BMA chemical activation by the bilateral microinjection of bicuculline methiodide (BMI; GABAA antagonist), blocked the increases in MAP and HR observed when an intruder rat was suddenly introduced into the cage of a resident rat, and confined to the small cage for 15min. Additionally, the increase in HR and MAP induced by BMA inhibition were eliminated by DMH chemical inhibition. Thus, our data reveal that the BMA is under continuous GABAergic influence, and that its hyperactivation can reduce the physiological response induced by a social novelty condition, possibly by inhibiting DMH neurons.

Social Stress Engages Neurochemically-Distinct Afferents to the Rat Locus Coeruleus Depending on Coping Strategy.

Stress increases vulnerability to psychiatric disorders, partly by affecting brain monoamine systems, such as the locus coeruleus (LC)-norepinephrine system. During stress, LC activity is coregulated by corticotropin-releasing factor (CRF) and endogenous opioids. This study identified neural circuitry that regulates LC activity of intruder rats during the resident-intruder model of social stress. LC afferents were retrogradely labeled with Fluorogold (FG) and rats were subjected to one or five daily exposures to an aggressive resident. Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK. In response to a single exposure, intruder rats assumed defeat with a relatively short latency (SL). LC neurons, PGI-ENK LC afferents, and CNA-CRF LC afferents were activated in these rats as indicated by increased c-fos expression. With repeated stress, rats exhibited either a SL or long latency (LL) to defeat and these strategies were associated with distinct patterns of neuronal activation. In SL rats, LC neurons were activated, as were CNA-CRF LC afferents but not PGI-ENK LC afferents. LL rats had an opposite pattern, maintaining activation of PGi-ENK LC afferents but not CNA-CRF LC afferents or LC neurons. Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system. This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies.

Clozapine, An Atypical Antipsychotic, Reduces The Contribution Of Brown Adipose Tissue (BAT) To Emotional Hyperthermia In Rats

Clozapine is an atypical antipsychotic drug used in patients with schizophrenia. Animal models of clozapine's actions are difficult to develop. BAT thermogenesis is increased by 5‐HT2A receptor activation and decreased by 5‐HT1A receptor activation in the CNS. Clozapine's interaction with these receptors predicts that the drug reduces BAT thermogenesis. We tested this in animal model in which BAT thermogenesis is initiated in a resident rat by introduction of an intruder rat confined to a small cage (Mohammed et al., 2012). ) Thermistor probes, connected to a headpiece, were placed in anterior mediastinum and interscapular BAT of anesthetized male Sprague‐Dawley rats (350‐450g. After 1 week the rat was maintained in a quiet, temperature controlled environment with ad libitum food and water. BAT and body temperatures were monitored via a swivel device. Clozapine was administered (0.03, 0.125, 0.5 and 2 mg/kg in 0.5 ml of acidified Ringer via subcutaneous catheter) and 30 min later the caged intruder was introduced for 30 min. At the lowest clozapine dose, the increase in BAT temperature (0.8±0.1C°) was greater (P<0.01) than the increase in body temperature (0.5±0.1C°). Clozapine, in a dose‐responsive manner, reduced the increase in BAT and body temperatures elicited during sudden confrontation with an intruder rat (log‐dose regression P<0001, R2 = 0.52, for BAT and P<0.01, R2 = 0.32 for body). Thus clozapine reduces BAT thermogenesis initiated by salient, threatening environmental events, thereby reducing emotional hyperthermia. BAT thermogenesis occurs in adult humans, possibly excessively in schizophrenics, so that our animal model may illuminate clozapine's therapeutic action and its contribute to obesity.Supported by NHMRC

High aggression in rats is associated with elevated stress, anxiety-like behavior, and altered catecholamine content in the brain

The social defeat paradigm involves aggressive encounters between Long–Evans (L–E) (resident) and Sprague–Dawley (S–D) (intruder) rats. Successful application of chronic social defeat stress in S–D rats is dependent upon selection of highly aggressive L–E rats. Half of the L–E rats screened for aggression did not meet the criterion for aggression (L–E rats performing a defeat, characterized by the intruder surrendering or acquiring a supine position for at least 3s). The observation of the differences in the level of aggression between age and weight matched L–E rats was quite compelling which led us to the present study. Herein, we measured behavioral differences between aggressor and non-aggressor L–E rats. We analyzed their anxiety-like behavior using open-field and elevated plus maze tests. We also measured aggression/violence-like behavior using two tests. In one, time taken to defeat the intruder S–D rat was recorded. In the second test, time taken to attack a novel object was compared between the two groups. We observed a significant increase in anxiety-like behavior in aggressor rats when compared to the non-aggressive group. Furthermore, time taken to defeat the intruder rat and to attack a novel object was significantly lower in aggressive L–E rats. Biochemical data suggests that heightened anxiety-like behavior and aggression is associated with increased plasma levels of corticosterones and elevated oxidative stress. Significant alterations in dopamine (DA), norepinephrine (NE) and epinephrine (EPI) were observed within the hippocampus, amygdala, and the prefrontal cortex, suggesting potential involvement of dopaminergic and noradrenergic systems in regulation of aggressive behaviors.

Head and cervical spine posture in behaving rats: implications for modeling human conditions involving the head and cervical spine.

The aim of this study was to define the temporal and spatial (postural) characteristics of the head and cervical vertebral column (spine) of behaving rats in order to better understand their suitability as a model to study human conditions involving the head and neck. Time spent in each of four behavioral postures was determined from video tape recordings of rats (n = 10) in the absence and presence of an intruder rat. Plain film radiographic examination of a subset of these rats (n = 5) in each of these postures allowed measurement of head and cervical vertebral column positions adopted by the rats. When single they were quadruped or crouched most (∼80%) of the time and bipedal either supported or free standing for only ∼10% of the time. The introduction of an intruder significantly (P < 0.0001) reduced the proportion of time rats spent quadruped (median, from 71% to 47%) and bipedal free standing (median, from 2.9% to 0.4%). The cervical spine was orientated (median, 25-75 percentile) near vertical (18.8°, 4.2°-30.9°) when quadruped, crouched (15.4°, 7.6°-69.3°) and bipedal supported (10.5°, 4.8°-22.6°) but tended to be less vertical oriented when bipedal free standing (25.9°, 7.7°-39.3°). The range of head positions relative to the cervical spine was largest when crouched (73.4°) and smallest when erect free standing (17.7°). This study indicates that, like humans, rats have near vertical orientated cervical vertebral columns but, in contrast to humans, they displace their head in space by movements at both the cervico-thoracic junction and the cranio-cervical regions.

Reduced brown adipose tissue thermogenesis during environmental interactions in transgenic rats with ataxin-3-mediated ablation of hypothalamic orexin neurons

Thermogenesis in brown adipose tissue (BAT) contributes to substantial increases in body temperature evoked by threatening or emotional stimuli. BAT thermogenesis also contributes to increases in body temperature that occur during active phases of the basic rest-activity cycle (BRAC), as part of normal daily life. Hypothalamic orexin-synthesizing neurons influence many physiological and behavioral variables, including BAT and body temperature. In conscious unrestrained animals maintained for 3 days in a quiet environment (24-26°C) with ad libitum food and water, we compared temperatures in transgenic rats with ablation of orexin neurons induced by expression of ataxin-3 (Orx_Ab) with wild-type (WT) rats. Both baseline BAT temperature and baseline body temperature, measured at the onset of BRAC episodes, were similar in Orx_Ab and WT rats. The time interval between BRAC episodes was also similar in the two groups. However, the initial slopes and amplitudes of BRAC-related increases in BAT and body temperature were reduced in Orx_Ab rats. Similarly, the initial slopes and amplitudes of the increases in BAT temperatures induced by sudden exposure to an intruder rat (freely moving or confined to a small cage) or by sudden exposure to live cockroaches were reduced in resident Orx_Ab rats. Constriction of the tail artery induced by salient alerting stimuli was also reduced in Orx_Ab rats. Our results suggest that orexin-synthesizing neurons contribute to the intensity with which rats interact with the external environment, both when the interaction is "spontaneous" and when the interaction is provoked by threatening or salient environmental events.

Witnessing traumatic events causes severe behavioral impairments in rats.

Witnessing a traumatic event but not directly experiencing it can be psychologically quite damaging. In North America alone, ∼30% of individuals who witness a traumatic event develop post-traumatic stress disorder (PTSD). While effects of direct trauma are evident, consequences of indirect or secondary trauma are often ignored. Also unclear is the role of social support in the consequences of these experiences. The social defeat paradigm, which involves aggressive encounters by a large Long-Evans male rat (resident) towards a smaller Sprague-Dawley male rat (intruder), is considered a rodent model of PTSD. We have modified this model to create a trauma witness model (TWM) and have used our TWM model to also evaluate social support effects. Basically, when an intruder rat is placed into the home cage of a resident rat, it encounters an agonistic behavior resulting in intruder subordination. The socially defeated intruder is designated the SD rat. A second rat, the cage mate of the SD, is positioned to witness the event and is the trauma witnessing (TW) rat. Experiments were performed in two different experimental conditions. In one, the SD and TW rats were cagemates and acclimatized together. Then, one SD rat was subjected to three sessions of social defeat for 7 d. TW rat witnessed these events. After each social defeat exposure, the TW and SD rats were housed together. In the second, the TW and SD rats were housed separately starting after the first defeat. At the end of each protocol, depression-anxiety-like behavior and memory tests were conducted on the SD and TW rats, blood withdrawn and specific organs collected. Witnessing traumatic events led to depression- and anxiety-like behavior and produced memory deficits in TW rats associated with elevated corticosterone levels.

Anti-aggressive effects of neuropeptide S independent of anxiolysis in male rats

Neuropeptide S (NPS) exerts robust anxiolytic and memory enhancing effects, but only in a non-social context. In order to study whether NPS affects aggressive behavior we used Wistar rats bred for low (LAB) and high (HAB) levels of innate anxiety-related behavior, respectively, which were both described to display increased levels of aggression compared with Wistar rats not selectively bred for anxiety (NAB). Male LAB, HAB, and NAB rats were tested for aggressive behavior toward a male intruder rat within their home cage (10 min, resident-intruder [RI] test). Intracerebroventricular (icv) infusion of NPS (1 nmol) significantly reduced inter-male aggression in LAB rats, and tended to reduce aggression in HAB and NAB males. However, local infusion of NPS (0.2 or 0.1 nmol NPS) into either the nucleus accumbens or the lateral hypothalamus did not influence aggressive behavior. Social investigation in the RI test and general social motivation assessed in the social preference paradigm were not altered by icv NPS (1 nmol). The anti-aggressive effect of NPS is most likely not causally linked to its anxiolytic properties, as intraperitoneal administration of the anxiogenic drug pentylenetetrazole decreased aggression in LAB rats whereas the anxiolytic drug diazepam did not affect aggression in HAB rats. Thus, although NPS has so far only been shown to exert effects on non-social behaviors, our results are the first demonstration of anti-aggressive effects of NPS in male rats.

Potential role of anxiety and stress in aggressive behavior in rats (839.2)

The social defeat paradigm involves aggressive encounters by a large Long‐Evans (LE) male rat (resident) toward a smaller Sprague‐Dawley (SD) male rat (intruder). Successful application of chronic social defeat stress to SD rats is dependent upon appropriate selection of LE rats with consistent levels of aggressive behaviors, as determined from the 3‐d screening process. During screening for the aggressor LE rats, we observed that half of all screened LE rats did not reach the criterion for aggression (LE rats performing a defeat, characterized by the intruder surrendering or acquiring a supine position for at least 3 sec). This difference in aggression between age and weight matched LE rats was startling and led us to the present study. Herein, we measured behavioral differences between the two groups of LE rats (aggressors and non‐aggressors). We analyzed their anxiety‐like behavior using open‐field and elevated plus maze tests. We also examined aggressive behavior in the two groups. (Aggression was measured by recording time taken to defeat the intruder SD rat and time taken to attack a novel object. We observed a significant increase in anxiety‐like behavior in aggressor rats when compared to the non‐aggressive group. Furthermore, time taken to defeat the intruder rat and to attack a novel object was significantly lower in aggressive LE rats. Biochemical data suggests occurrence of significant differences in the levels of stress (assessed via corticosterone assay) and oxidative stress (analyzed via 8‐isoprostane and protein carbonylation) in rats associated with aggressive and non‐aggressive behaviors.Grant Funding Source: NIH‐R15‐G103327