Standardised ginseng extract G115® potentiates the antidepressant-like properties of fluoxetine in the forced swim test.

OBJECTIVE: Ginsenosides, biologically active components of the root of Panax ginseng, have been reported to have therapeutic benefits in a number of disease states including psychiatric conditions such as major depressive disorder. Our objective was to determine if a standardised commercial ginseng extract, G115®, could reduce the signs of behavioural despair commonly observed in animal models of depression either alone or in combination with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. METHODS: Male Sprague-Dawley (SD) rats (N = 51) were divided into four groups: vehicle control, G115® ginseng root extract, fluoxetine and fluoxetine plus G115®. Rats were trained to voluntarily consume treatments twice daily for 14 days and were then tested in an open field (OF), elevated plus maze (EPM) and forced swim test (FST). Post-mortem hippocampal and prefrontal cortex tissue was analysed for expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) by western blot. RESULTS: One-way Analysis of Variance revealed no significant group differences in the OF or plus-maze performance on any variable examined. In the FST, fluoxetine significantly reduced immobility time and increased latency to immobility. The effects of fluoxetine were further significantly potentiated by co-administration of G115®. Post-mortem tissue analysis revealed significant group differences in BDNF expression in the left hippocampus and left prefrontal cortex without any accompanying changes in TrkB expression. CONCLUSIONS: We conclude that oral G115® significantly potentiates the antidepressant-like effect of fluoxetine in the FST in the absence of potentially confounding effects on locomotion and anxiety.

Rats (Rattus norvegicus) find occupancy of a restraint tube rewarding.

Two experiments evaluated whether rats' occupancy of a restraint tube is reinforcing. In Experiment 1, each rat in the 0-min group moved freely in a chamber where a wall blocked access to a restraint tube. After 10 min the wall was removed, permitting 15 min of chamber access and tube entry. The other 2 groups were locked in the tube for 10 and 20 min respectively before release into the chamber for 15 min. Across sessions, rats locked up for 10 and 20 min entered the tube more frequently than rats in the 0-min group, and during the first 2 sessions rats in the 20-min group stayed in the tube longer than the other groups. Over sessions this difference disappeared. However, for all groups and sessions the mean percentage of session time in the tube exceeded chance expectations. This result suggests tube occupation was reinforcing. In Experiment 2's Phase 1, rats could enter an open tube. On exiting, the tube door closed. A lever press opened the door for the rest of the 1-hr session. In Phase 2, these rats were locked in the tube for 10 min before the door opened. Upon exiting, the door closed. As in Phase 1, a lever press opened the door for the rest of the session. The latency between pressing and tube entry decreased over sessions, indicating that tube entry reinforced lever pressing. These results are difficult to reconcile with accounts of rat empathy based on the thesis that tube restraint distresses occupants.

Ultrasonic vocalization in female rats: A comparison among three outbred stocks from pups to adults.

Long Evans (LE), Sprague-Dawley (SD) and Wistar (WU) are outbred rat stocks, which differ in terms of brain, physiology, pharmacological reactivity and behavior. Extending our previous work with males from these stocks, we here report the analysis of ultrasonic vocalizations (USV) in females. Identical to our previous studies, we tested them as pups for 40-kHz calls during short-term isolation, as juveniles for appetitive 50-kHz calls during a cage test or when being tickled, and finally as adults for 22-kHz calls in a fear conditioning paradigm. Stock differences were obtained in all four tests, albeit with different patterns: As pups, WU rats emitted more calls and spent more time calling than SD or LE rats. Furthermore, LE rats emitted calls with shorter durations, whereas SD emitted calls with lower peak frequencies and less frequency modulation. Furthermore, stock differences in call sub-types were detected. In the cage test, 50-kHz calls were most frequent in WU and rather few in LE rats. Call durations were longer in WU rats. When being tickled, SD females emitted calls with shorter durations and lower peak frequencies. Also, frequency modulation and call amplitude was higher in LE. Finally, the fear-conditioning test led to partly unexpected results, since many females, especially WU, did not emit 22-kHz calls even during the conditioning phase, but all stocks showed the expected behavioral immobility and responded with audible calls to the aversive shocks. These results are discussed with respect to factors of testing, development, gender, and stock.

Potential of Intranasal Neuropeptide Y (NPY) and/or Melanocortin 4 Receptor (MC4R) Antagonists for Preventing or Treating PTSD.

There is a great need for effective treatment options for post-traumatic stress disorder (PTSD). Neuropeptide Y (NPY) is associated with resilience to traumatic stress. MC4R antagonists, such as HS014, also reduce response to stress. Both regulate stress-responsive systems - the hypothalamic-pituitary-axis (HPA) and the noradrenergic nervous system and their associated behaviors. Therefore, we examined if their intranasal delivery to brain could attenuate development of PTSD-related symptoms in single prolonged stress (SPS) rodent PTSD model. Three regimens were used: (1) prophylactic treatment 30 min before SPS stressors, (2) early intervention right after SPS stressors, (3) therapeutic treatment when PTSD behaviors are manifested 1 wk or more after the traumatic stress. NPY delivered by regimen 1 or 2 prevented SPS-triggered elevation in anxiety, depressive-like behavior, and hyperarousal and reduced dysregulation of HPA axis. Hypothalamic CRH mRNA and GR in ventral hippocampus were significantly induced in vehicle- but not NPY-treated group. NPY also prevented hypersensitivity of LC/NE system to novel mild stressor and induction of CRH in amygdala. Some of these impairments were also reduced with HS014, alone or together with NPY. When given after symptoms were manifested (regiment 3), NPY attenuated anxiety and depressive behaviors. This demonstrates strong preclinical proof of concept for intranasal NPY, and perhaps MC4R antagonists, for non-invasive early pharmacological interventions for PTSD and comorbid disorders and possibly also as therapeutic strategy.

The different baseline characteristics of cognitive behavior test between Mongolian gerbils and rats.

The Mongolian gerbil is a popular laboratory animal useful across many research fields. In the area of cognitive behavioral research the gerbil have been shown exhibit an anxiety-like profile on the elevated plus-maze, and they could be useful as an animal model for testing anxiolytics and antidepressants. However, there are few reports that thoroughly describe the behavioral characteristics of the gerbils in common cognitive behavior tests. In the present study, we used 7 behavior tests to detect the baseline characteristics of the gerbils and compare them to the Sprague Dawley rats. Collectively, the gerbils showed significantly different behavior characteristics in the open field test, elevated plus maze, grip strength, social interaction and fear conditioning compared to the rats. However, no difference was found between gerbils and rats in sucrose preference or Barnes maze test. The data showed that the Mongolian gerbil exhibited higher social interaction and exploratory activity, but lower conditioning fear and grip strength compared with the rats. These results indicate that the gerbil may be a sensitive animal model in behavioral brain research particularly in the areas of anxiety and fear.

Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress-related metabolic pathways.

Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs (such as clozapine, risperidone and aripiprazole) on stress, we compared neurochemical profile variations in the PFC and hippocampus between rat models of chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS)-based metabolomic approach and a multicriteria assessment. We identified a number of stress-induced biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid, allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines (PEs), corticosterone and progesterone. Specifically, pathway enrichment and correlation analyses suggested that stress induces oxidative damage by disturbing the creatine-phosphocreatine circuit and purine pathway, leading to excessive membrane breakdown. Moreover, our data suggested that the AAPDs tested partially restore stress-induced deficits by increasing the levels of creatine, progesterone and PEs. Thus, the present findings provide a theoretical basis for the hypothesis that a combined therapy using adenosine triphosphate fuel, antioxidants and omega-3 fatty acids as supplements may have synergistic effects on the therapeutic outcome following AAPD treatment.

The Psychological Effects of Rapid Aeromedical Evacuation in a Predator Exposure Animal Model of Post-Traumatic Stress Disorder.

Recent conflicts have contributed to an escalation in combat-related psychiatric disorders, including post-traumatic stress disorder (PTSD). Although technological advances have increased the speed from which battlefield injuries reach definitive care, mental health conditions have continued to rise. This study sought to analyze the effects of flight stressors and the lack of a postcombat decompression period on stress-related behavior. We hypothesized that a 1-week decompression period before flight would attenuate stress-related behavior compared to no decompression. PTSD-like effects were induced in male Sprague-Dawley rats. The rats were placed in cages with a cat on two occasions during the 31-day stress regimen. PTSD rats were also subjected to daily cage cohort changes. At the conclusion of the stress regimen, the animals were flown on a military aircraft (WC-130J) for 4 hours. They were subsequently tested via elevated plus-maze and fear conditioning system. The PTSD animals that experienced a decompression period demonstrated decreased anxiety as compared to the no decompression group. In contrast, no difference was noted between the non-PTSD decompression and no decompression flight and no flight groups. The decrease in anxiety between the PTSD flight groups suggests that a decompression period before evacuation may minimize the potential for PTSD development.

Laboratory domestication changed the expression patterns of oxytocin and vasopressin in brains of rats and mice.

The process of domestication is recognized to exert significant effects on the social behaviors of various animal species, including defensive and cognitive behaviors that are closely linked to the expression of oxytocin (OT) and vasopressin (AVP) in selected areas of the brain. However, it is still unclear whether the behavioral changes observed under domestication have resulted in differences in the neurochemical systems that regulate them. In this study, we compared the differences in distribution patterns and regional quantities of OT and/or AVP staining in the forebrains of wild and laboratory strains of rats and mice. Our results indicated that, in the anterior hypothalamus (AH), laboratory strains showed significantly higher densities of OT-ir (immunoreactive) and AVP-ir cells than wild strains, while no significant difference in the densities of those cells in the lateral hypothalamus (LH) was detected between wild and laboratory strains. Laboratory strains showed higher densities of OT-ir and AVP-ir cells than wild strains in the medial preoptic area (MPOA), and differed in almost every MPOA subnucleus. Our results suggest that domestication significantly alters the expression of OT and AVP in related brain areas of laboratory rats and mice, an observation that could explain the identified changes in behavioral patterns.

Repeated forced swim stress differentially affects formalin-evoked nociceptive behaviour and the endocannabinoid system in stress normo-responsive and stress hyper-responsive rat strains.

Repeated exposure to a homotypic stressor such as forced swimming enhances nociceptive responding in rats. However, the influence of genetic background on this stress-induced hyperalgesia is poorly understood. The aim of the present study was to compare the effects of repeated forced swim stress on nociceptive responding in Sprague-Dawley (SD) rats versus the Wistar Kyoto (WKY) rat strain, a genetic background that is susceptible to stress, negative affect and hyperalgesia. Given the well-documented role of the endocannabinoid system in stress and pain, we investigated associated alterations in endocannabinoid signalling in the dorsal horn of the spinal cord and amygdala. In SD rats, repeated forced swim stress for 10 days was associated with enhanced late phase formalin-evoked nociceptive behaviour, compared with naive, non-stressed SD controls. In contrast, WKY rats exposed to 10 days of swim stress displayed reduced late phase formalin-evoked nociceptive behaviour. Swim stress increased levels of monoacylglycerol lipase (MAGL) mRNA in the ipsilateral side of the dorsal spinal cord of SD rats, an effect not observed in WKY rats. In the amygdala, swim stress reduced anandamide (AEA) levels in the contralateral amygdala of SD rats, but not WKY rats. Additional within-strain differences in levels of CB1 receptor and fatty acid amide hydrolase (FAAH) mRNA and levels of 2-arachidonylglycerol (2-AG) were observed between the ipsilateral and contralateral sides of the dorsal horn and/or amygdala. These data indicate that the effects of repeated stress on inflammatory pain-related behaviour are different in two rat strains that differ with respect to stress responsivity and affective state and implicate the endocannabinoid system in the spinal cord and amygdala in these differences.

Sex differences in the stress response in SD rats.

Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and ß, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression.

Ultrasonic vocalizations in rats anticipating circadian feeding schedules.

Rats readily learn to anticipate a reward signaled by an external stimulus. Anticipatory behaviors evoked by conditioned stimuli include 50 kHz ultrasonic vocalizations (USVs), a proposed behavioral correlate of positive affect and activation of midbrain dopamine pathways. Rats can also anticipate a reward, such as food, provided once daily, without external cueing. Anticipation of a daily reward exhibits formal properties of a circadian rhythm. The neural circuits that regulate the timing and amplitude of these rhythms remain an open question, but evidence suggests a role for dopamine. To gain further insight into the neural and affective correlates of circadian food anticipatory rhythms, we made 2h and 24h USV recordings in rats fed 2h/day in the light period, a procedure that induces robust anticipation 2-3h before mealtime. Potential interactions between internal and external time cues in USV production were evaluated by inclusion of a 3 kHz tone 15 min before mealtime. Prior to scheduled feeding, spontaneous 50 kHz USVs were rare during the light period. During scheduled feeding, flat and frequency modulated (FM) 50kHz USVs occurred prior to and during mealtime. FM USVs were more closely related to anticipation, while flat USVs were more dependent on food access. USVs also occurred during spontaneous waking at other times of day. The tone did not evoke USVs but did modulate activity. Behavioral anticipation of a daily meal is accompanied by USVs consistent with a positive affective state and elevated dopamine transmission.

Domestication and diversification: a comparative analysis of the play fighting of the Brown Norway, Sprague-Dawley, and Wistar laboratory strains of (Rattus norvegicus).

Laboratory strains of rats are a commonly used subject to study play behavior. Recent research has shown that play in one laboratory strain of rat (e.g., Long-Evans hooded) differs in a number of ways from its wild counterparts. These findings suggest that domestication affects some aspects of play behavior. However, there are multiple strains of laboratory rats, which have been domesticated through different lineages all derived from wild rats and it cannot be assumed that all domestic strains are identical in their play. Therefore, the aim of this study was to compare the play behavior of three other strains of laboratory rats (e.g., Wistar, Sprague-Dawley, and Brown Norway). All strains were similar to each other as they all engaged in high frequencies of play, tolerated similar interanimal distances before initiating playful defense and displayed similar acrobatic capacities, suggesting domestication produces some common changes in play and other factors that influence play. However, strains differed significantly from one another in the use of tactics that promote bodily contact during play. Indeed, in this regard, some strains were more similar to wild rats than others, suggesting that some domestication-induced changes are either unique or more prominent in some laboratory strains than others. Such a mosaic pattern of transformation not only offers the possibility of using strain differences to characterize the genetic factors contributing to different facets of play, but also cautions researchers from making rat-general conclusions from studies on any one strain.

Rats exhibit reference-dependent choice behavior.

Human preferences depend on whether a chosen outcome appears to be a loss or a gain compared with what had been expected, i.e., in comparison to a reference point. Because reference dependence has such a strong influence on human decision-making, it is important to uncover its origins, which will in turn help delineate the underlying mechanisms. It remains unknown whether rats use reference points in decision-making, and yet, the study of rats could help address the question of whether reference dependence is evolutionarily conserved among mammals and could provide a nonhuman animal model to investigate the neural mechanisms underlying this important cognitive process. The aim of the current study was to determine whether rats show reference-dependent choice behavior. We developed a novel paradigm by modifying the "T" maze by installing "pockets" to the left and right of the "T" stem that held reward pellets so rats would potentially develop reference values for each option prior to choice. We found that the rats were indeed sensitive to the way alternatives were presented. That is, they exhibited reference-dependent choice behavior by avoiding the choice option framed as a loss (e.g., having four reward pellets in the pocket, but receiving only one), at least under conditions with certain outcomes and clear differences between the reference and outcome quantities. Despite the small number of rats in this study, this species-level capacity suggests that reference dependence in general and loss aversion in particular may be conserved traits that evolved at or before the emergence of mammals.

Feeding and metabolic consequences of scheduled consumption of large, binge-type meals of high fat diet in the Sprague-Dawley rat.

Providing rats and mice with access to palatable high fat diets for a short period each day induces the consumption of substantial binge-like meals. Temporal food intake structure (assessed using the TSE PhenoMaster/LabMaster system) and metabolic outcomes (oral glucose tolerance tests [oGTTs], and dark phase glucose and insulin profiles) were examined in Sprague-Dawley rats given access to 60% high fat diet on one of 3 different feeding regimes: ad libitum access (HF), daily 2 h-scheduled access from 6 to 8 h into the dark phase (2 h-HF), and twice daily 1 h-scheduled access from both 1-2 h and 10-11 h into the dark phase (2×1 h-HF). Control diet remained available during the scheduled access period. HF rats had the highest caloric intake, body weight gain, body fat mass and plasma insulin. Both schedule-fed groups rapidly adapted their feeding behaviour to scheduled access, showing large meal/bingeing behaviour with 44% or 53% of daily calories consumed from high fat diet during the 2 h or 2×1 h scheduled feed(s), respectively. Both schedule-fed groups had an intermediate caloric intake and body fat mass compared to HF and control (CON) groups. Temporal analysis of food intake indicated that schedule-fed rats consumed large binge-type high fat meals without a habitual decrease in preceding intake on control diet, suggesting that a relative hypocaloric state was not responsible or required for driving the binge episode, and substantiating previous indications that binge eating may not be driven by hypothalamic energy balance neuropeptides. In an oGTT, both schedule-fed groups had impaired glucose tolerance with higher glucose and insulin area under the curve, similar to the response in ad libitum HF fed rats, suggesting that palatable feeding schedules represent a potential metabolic threat. Scheduled feeding on high fat diet produces similar metabolic phenotypes to mandatory (no choice) high fat feeding and may be a more realistic platform for mechanistic study of diet-induced obesity.

Desire for social contact, not empathy, may explain "rescue" behavior in rats.

Ben-Ami Bartal et al. (Science 334:1427-1430, 2011) showed that a rat in an open space (free rat) would touch the front door of a restraining tube to open its rear door, thereby enabling a rat trapped within (trapped rat) to enter a larger space that was farther away from the free rat. Since opening the rear door distanced the trapped rat from the free rat, Ben-Ami Bartal et al. argued free-rat behavior could not be motivated by the pursuit of social contact. Instead, this rat was empathically motivated, its goal being to reduce the presumed distress of the rat trapped in the restraining tube. In two experiments, we show that (a) a free rat will not learn to touch the front door to open the rear door when it is the first condition of the experiment; (b) over time, a trapped rat will often return to a restraining tube despite its presumed aversiveness; and (c) a free rat experienced in touching the front door will continue to touch it even if touching does not free the trapped rat. We explain these results and Ben-Ami Bartal et al.'s in terms of two processes, neophobia and the pursuit of social contact. When first placed in a restraining tube, neophobia causes the trapped rat to escape the tube when the rear door is opened. Across sessions, neophobia diminishes, permitting the rats' pursuit of social contact to emerge and dominate free- and trapped-rat behavior.

Social transmission of Pavlovian fear: fear-conditioning by-proxy in related female rats.

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a foot-shock) leads to associative learning such that the tone alone will elicit a conditioned response (e.g., freezing). Individuals can also acquire fear from a social context, such as through observing the fear expression of a conspecific. In the current study, we examined the influence of kinship/familiarity on social transmission of fear in female rats. Rats were housed in triads with either sisters or non-related females. One rat from each cage was fear conditioned to a tone CS+ shock US. On day two, the conditioned rat was returned to the chamber accompanied by one of her cage mates. Both rats were allowed to behave freely, while the tone was played in the absence of the foot-shock. The previously untrained rat is referred to as the fear-conditioned by-proxy (FCbP) animal, as she would freeze based on observations of her cage-mate's response rather than due to direct personal experience with the foot-shock. The third rat served as a cage-mate control. The third day, long-term memory tests to the CS were performed. Consistent with our previous application of this paradigm in male rats (Bruchey et al. in Behav Brain Res 214(1):80-84, 2010), our results revealed that social interactions between the fear conditioned and FCbP rats on day two contribute to freezing displayed by the FCbP rats on day three. In this experiment, prosocial behavior occurring at the termination of the cue on day two was significantly greater between sisters than their non-sister counterparts, and this behavior resulted in increased freezing on day three. Our results suggest that familiarity and/or kinship influences the social transmission of fear in female rats.

Prospective memory in the rat.

The content of prospective memory is comprised of representations of an action to perform in the future. When people form prospective memories, they temporarily put the memory representation in an inactive state while engaging in other activities, and then activate the representation in the future. Ultimately, successful activation of the memory representation yields an action at an appropriate, but temporally distant, time. A hallmark of prospective memory is that activation of the memory representation has a deleterious effect on current ongoing activity. Recent evidence suggests that scrub jays and non-human primates, but not other species, are capable of future planning. We hypothesized that prospective memory produces a selective deficit in performance at the time when rats access a memory representation but not when the memory representation is inactive. Rats were trained in a temporal bisection task (90 min/day). Immediately after the bisection task, half of the rats received an 8-g meal (meal group) and the other rats received no additional food (no-meal group). Sensitivity to time in the bisection task was reduced as the 90-min interval elapsed for the meal group but not for the no-meal group. This time-based prospective-memory effect was not based on response competition, an attentional limit, anticipatory contrast, or fatigue. Our results suggest that rats form prospective memories, which produces a negative side effect on ongoing activity.

Handling of adolescent rats improves learning and memory and decreases anxiety.

Some environmental interventions can result in physiologic and behavioral changes in laboratory animals. In this context, the handling of adolescent or adult rodents has been reported to influence exploratory behavior and emotionality. Here we examined the effects of handling on memory and anxiety levels of adolescent rats. Male Sprague-Dawley rats (age, 60 d) were divided into a control group and a handled group, which were handled for 5 min daily, 5 d per week, for 6 wk. During handling bouts, the rat was removed from its cage, placed in the experimenter's lap or on the top of a table, and had its neck and back gently stroked by the experimenter's fingers. During week 6, each rat's anxiety level was evaluated in the elevated plus-maze (EPM) test. Learning and memory were evaluated 48 h later, by measuring escape latency in the elevated plus-maze test. Plasma corticosterone and catecholamine levels were measured also. Norepinephrine levels were lower in the handled rats compared with control animals, with no differences in epinephrine and corticosterone. As compared with the control rats, the handled rats showed increases in the percentage of time spent in the open arms of the test apparatus, percentage of entries into open arms, and number of visits to the end of the open arms and decreases in the latency of the first open arm entry. Escape latency was lower in the handled rats compared with control rats in both the first and second trials. The data obtained suggest that handling decreases anxiety levels and improves learning skills and memory in rats.

Endocrinological differences between Hatano high- and low-avoidance rats during early two-way avoidance acquisition.

Hatano high (HAA)- and low (LAA)-avoidance rats were selected from Sprague-Dawley rats genetically on the basis of their active avoidance behavior in a shuttle-box test. The purpose of this study was to investigate stress-related alterations of hormones corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP), prolactin, and adrenocorticotropin (ACTH) in the brain and blood during early avoidance acquisition using two lines of Hatano rats. In paraventricular nucleus (PVN) of the hypothalamus, the CRH levels in HAA rats were significantly increased after shuttle-box tasks compared with before the tasks, whereas the CRH levels in LAA rats significantly decreased after shuttle-box tasks compared with before the tasks. In the HAA rats, the CRH and AVP levels in the median eminence decreased after shuttle-box tasks, whereas there were no significant differences in the levels between before and after shuttle-box tasks in LAA rats. The plasma concentrations of ACTH were significantly higher in HAA rats than in LAA rats after shuttle-box tasks. These results show that the response of CRH-ACTH was higher in HAA rats than in LAA rats. This phenotype may be an important reason for the high avoidance rates of shuttle-box tasks in HAA rats. These endocrine differences in early avoidance acquisition may be involved in regulation of their avoidance responses in the shuttle-box task.

The effects of reward quality on risk-sensitivity in Rattus norvegicus.

Risk-sensitive foraging theory (RSFT) was developed to explain a choice between a variable (risk-prone) or constant (risk-averse) option. In the RSFT literature, qualitative shifts in risk-sensitivity have been explained by fluctuations in daily caloric energy budget (DEB). The DEB rule describes foragers' choices as being based on fitness and rate of gain. If the DEB rule is correct, rewards that differ in caloric returns should cause differences in foragers' sensitivity to risk. However, few studies have explored the influence of reward quality on risk-sensitivity in mammals. The present study was designed to examine the effects of reward quality on risk-sensitivity when reward magnitude, delay to reward, body mass, and response effort were controlled. Results from the current study demonstrated that subjects rewarded with a high calorie reward (i.e., sugar) made significantly fewer choices for a variable option than subjects rewarded with a lower calorie reward (i.e., grain). These results are consistent with the predictions of the DEB rule, and add to the RSFT literature where reward quality was manipulated by describing difference in risk-sensitivity in mammals. Suggestions for future research include an examination of risk-sensitivity where flavor and caloric return are manipulated.