Efficient neural decoding of self-location with a deep recurrent network.

Place cells in the mammalian hippocampus signal self-location with sparse spatially stable firing fields. Based on observation of place cell activity it is possible to accurately decode an animal's location. The precision of this decoding sets a lower bound for the amount of information that the hippocampal population conveys about the location of the animal. In this work we use a novel recurrent neural network (RNN) decoder to infer the location of freely moving rats from single unit hippocampal recordings. RNNs are biologically plausible models of neural circuits that learn to incorporate relevant temporal context without the need to make complicated assumptions about the use of prior information to predict the current state. When decoding animal position from spike counts in 1D and 2D-environments, we show that the RNN consistently outperforms a standard Bayesian approach with either flat priors or with memory. In addition, we also conducted a set of sensitivity analysis on the RNN decoder to determine which neurons and sections of firing fields were the most influential. We found that the application of RNNs to neural data allowed flexible integration of temporal context, yielding improved accuracy relative to the more commonly used Bayesian approaches and opens new avenues for exploration of the neural code.

Relationship between Plasma Albumin Concentration and Plasma Volume in 5 Inbred Rat Strains.

Using the Evans Blue procedure, we previously found strain-related differences in plasma volumes in 5 inbred rat strains. Because albumin binds strongly with Evans blue, this protein is important in the Evans blue method of plasma volume determination. Therefore, we speculated that interstrain differences in plasma albumin concentration (PAC) could distort calculated plasma volumes. To address this concern, we used ELISA techniques to measure PAC in these inbred rat strains. In study A, the blood volume was measured by using Evans blue dye, and albumin was measured at the start of hemorrhage. In study B, blood volume was not measured, and albumin was measured twice, near the start and end of hemorrhage (approximately 14 min apart). Neither study revealed any interstrain differences in PAC, which decreased after hemorrhage in all 5 strains. No correlation was found between PAC and plasma volume, survival time, blood lactate, or blood base excess. Percentage changes in PAC during hemorrhage were greater in salt-sensitive compared with Lewis rats. Moreover, these percentage changes were associated with survival time in Fawn hooded hypertensive rats. Our data show that the plasma volumes we measured previously were not misrepresented due to variations in PAC.

Spatial learning in the genetically heterogeneous NIH-HS rat stock and RLA-I/RHA-I rats: revisiting the relationship with unconditioned and conditioned anxiety.

To characterize learning/memory profiles for the first time in the genetically heterogeneous NIH-HS rat stock, and to examine whether these are associated with anxiety, we evaluated NIH-HS rats for spatial learning/memory in the Morris water maze (MWM) and in the following anxiety/fear tests: the elevated zero-maze (ZM; unconditioned anxiety), a context-conditioned fear test and the acquisition of two-way active avoidance (conditioned anxiety). NIH-HS rats were compared with the Roman High- (RHA-I) and Low-Avoidance (RLA-I) rat strains, given the well-known differences between the Roman strains/lines in anxiety-related behavior and in spatial learning/memory. The results show that: (i) As expected, RLA-I rats were more anxious in the ZM test, displayed more frequent context-conditioned freezing episodes and fewer avoidances than RHA-I rats. (ii) Scores of NIH-HS rats in these tests/tasks mostly fell in between those of the Roman rat strains, and were usually closer to the values of the RLA-I strain. (iii) Pigmented NIH-HS (only a small part of NIH-HS rats were albino) rats were the best spatial learners and displayed better spatial memory than the other three (RHA-I, RLA-I and NIH-HS albino) groups. (iv) Albino NIH-HS and RLA-I rats also showed better learning/memory than the RHA-I strain. (v) Within the NIH-HS stock, the most anxious rats in the ZM test presented the best learning and/or memory efficiency (regardless of pigmentation). In summary, NIH-HS rats display a high performance in spatial learning/memory tasks and a passive coping strategy when facing conditioned conflict situations. In addition, unconditioned anxiety in NIH-HS rats predicts better spatial learning/memory.

Differential effects of cocaine on extracellular signal-regulated kinase phosphorylation in nuclei of the extended amygdala and prefrontal cortex of psychogenetically selected Roman high- and low-avoidance rats.

Roman high (RHA)- and low (RLA)-avoidance rats are selectively bred for rapid vs. poor acquisition of active avoidance, respectively, and differ markedly in emotional reactivity, coping style, and behavioral and neurochemical responses to morphine and psychostimulants. Accordingly, acute cocaine induces more robust increments in locomotion and dopamine output in the nucleus accumbens shell (AcbSh) of RHA than of RLA rats. Cocaine induces short- and long-term neuronal plasticity via activation of the extracellular signal-regulated kinase (ERK) pathway. This study compares the effects of acute cocaine on ERK phosphorylation (pERK) in limbic brain areas of Roman rats. In RHA but not RLA rats, cocaine (5 mg/kg) increased pERK in the infralimbic prefrontal cortex and AcbSh, two areas involved in its acute effects, but did not modify pERK in the prelimbic prefrontal cortex and Acb core, which mediate the chronic effects of cocaine. Moreover, cocaine failed to affect pERK immunolabeling in the bed nucleus of stria terminalis pars lateralis and central amygdala of either line but increased it in the basolateral amygdala of RLA rats. These results extend to pERK expression previous findings on the greater sensitivity to acute cocaine of RHA vs. RLA rats and confirm the notion that genetic factors influence the differential responses of the Roman lines to addictive drugs. Moreover, they support the view that the Roman lines are a useful tool to investigate the molecular underpinnings of individual vulnerability to drug addiction.

Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease.

A behavioral comparison of the common laboratory rat strains Lister Hooded, Lewis, Fischer 344 and Wistar in an automated homecage system.

Behavioral characterization is an important part of establishing novel animal models, but classical behavioral tests struggle to reveal conclusive results due to problems with both reproducibility and validity. On the contrary, automated homecage observations are believed to produce robust outcomes that relate more to natural animal behavior. However, information on the behavior of background strains from such observations, which could provide important reference material, is rare. For this reason, we compared the behavior of the commonly used Lister Hooded, Lewis, Fischer 344 and Wistar rats during 70 h of exposure to an automated homecage system at 2, 4 and 6 months of age. We found considerable strain differences in metabolic parameters, novelty-induced and baseline activity-related behavior as well as differences in the development of these parameters with age. The results are discussed in terms of advantages and disadvantages of the system compared to classical behavioral tests, as well as the system's ability to recreate common findings in literature.

Do variations in mast cell hyperplasia account for differences in radiation-induced lung injury among different mouse strains, rats and nonhuman primates?

The role of mast cell infiltrates in the pathology of radiation damage to the lung has been a subject of continuing investigation over the past four decades. This has been accompanied by a number of proposals as to how mast cells and the secretory products thereof participate in the generation of acute inflammation (pneumonitis) and the chronic process of collagen deposition (fibrosis). An additional pathophysiology examines the possible connection between mast cell hyperplasia and pulmonary hypertension through the release of vasoactive mediators. The timing and magnitude of pneumonitis and fibrosis are known to vary tremendously among different genetic mouse strains and animal species. Therefore, we have systematically compared mast cell numbers in lung sections from nine mouse strains, two rat strains and nonhuman primates (NHP) after whole thorax irradiation (WTI) at doses ranging from 10-15 Gy and at the time of entering respiratory distress. Mice of the BALB/c strain had a dramatic increase in interstitial mast cell numbers, similar to WAG/Rij and August rats, while relatively low levels of mast cell infiltrate were observed in other mouse strains (CBA, C3H, B6, C57L, WHT and TO mice). Enumeration of mast cell number in five NHPs (rhesus macaque), exhibiting severe pneumonitis at 17 weeks after 10 Gy WTI, also indicated a low response shared by the majority of mouse strains. There appeared to be no relationship between the mast cell response and the strain-dependent susceptibility towards pneumonitis or fibrosis. Further investigations are required to explore the possible participation of mast cells in mediating specific vascular responses and whether a genetically diverse mast cell response occurs in humans.

Strong genetic influences on measures of behavioral-regulation among inbred rat strains.

A fundamental challenge for any complex nervous system is to regulate behavior in response to environmental challenges. Three measures of behavioral-regulation were tested in a panel of eight inbred rat strains. These measures were: (1) sensation seeking as assessed by locomotor response to novelty and the sensory reinforcing effects of light onset, (2) attention and impulsivity, as measured by a choice reaction time task and (3) impulsivity as measured by a delay discounting task. Deficient behavioral-regulation has been linked to a number of psychopathologies, including ADHD, Schizophrenia, Autism, drug abuse and eating disorders. Eight inbred rat strains (August Copenhagen Irish, Brown Norway, Buffalo, Fischer 344, Wistar Kyoto, Spontaneous Hypertensive Rat, Lewis, Dahl Salt Sensitive) were tested. With n = 9 for each strain, we observed robust strain differences for all tasks; heritability was estimated between 0.43 and 0.66. Performance of the eight inbred rat strains on the choice reaction time task was compared to the performance of outbred Sprague Dawley (n = 28) and Heterogeneous strain rats (n = 48). The results indicate a strong genetic influence on complex tasks related to behavioral-regulation and indicate that some of the measures tap common genetically driven processes. Furthermore, our results establish the potential for future studies aimed at identifying specific alleles that influence variability for these traits. Identification of such alleles could contribute to our understanding of the molecular genetic basis of behavioral-regulation, which is of fundamental importance and likely contributes to multiple psychiatric disorders.

Structural characteristics of adenohypophysis in hypertensive ISIAH rats in early ontogeny.

Comparative morphological study of the adenohypophysis was conducted in 3-week-old normotensive WAG and hypertensive ISIAH rats (prehypertension period) to elucidate the role of the adenohypophysis in the development of essential hypertension. Morphometric analysis revealed ultrastructural signs of functional activation of somatotrophs, gonadotrophs, and corticotrophs in ISIAH rats. These peculiarities of structural organization of adenohypophysis in hypertensive rats can attest to enhanced response of the hypothalamic-pituitary-adrenal axis in these animals to natural stress associated with their transition to independent feeding. Increased stress sensitivity during the prehypertensive period of postnatal ontogeny contributes to the development of arterial hypertension.

Lactation deficit in OFA hr/hr rats may be caused by differential sensitivity to stress compared with Wistar and Sprague Dawley rats.

OFA hr/hr (OFA) rats present a major lactation deficit that impairs offspring survival. To explore whether abnormal stress responsiveness causes this deficit, we compared their hormonal (prolactin, progesterone, and corticosterone) responses to stress (room change and 2-min ether exposure) with those of Wistar and Sprague Dawley (SD) rats. We tested responses during the estrous cycle, pregnancy, lactation, after ovariectomy, and ovarian steroid hormone priming, and responses to suckling. We evaluated hypothalamic expression of receptors for prolactin (PRLRlong) and the isoforms of receptors for progesterone (PRA and B) and estrogen (ERα and ß) in late pregnancy. We tested whether administration of an anxiolytic (diazepam) improved lactation. Ether exposure increased circulating levels of the three hormones in the three strains of rats, cycling and ovariectomized, but was less effective in pregnancy and lactation. Elevated estrogen level (estrus and estradiol-treated ovariectomized rats) potentiated the prolactin response more in SD and OFA rats than in Wistar rats. Elevated progesterone level (late pregnancy, lactation, progesterone-treated ovariectomized rats) inhibited the prolactin response less in OFA than in SD or Wistar rats. Ether exposure inhibited the prolactin and oxytocin responses to suckling only in OFA rats. Diazepam treatment increased pup survival rate and the prolactin response to suckling. Hypothalamic total PR mRNA content, assayed by RT-PCR, was higher in pregnant OFA rats compared with SD and Wistar rats, but the PRB/PRA protein ratio determined by Western blot was lowest in Wistar rats, intermediate in OFA rats, and highest in SD rats. The heightened sensitivity to stress of lactating OFA rats may contribute to their lactational deficit and be caused by a combination of hypoprolactinemia and reduced inhibitory capacity of progesterone.

Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains.

The purpose of the present study was to evaluate for the first time the stress-induced hypothalamus-pituitary-adrenal (HPA), adrenocorticotropic hormone (ACTH), corticosterone and prolactin responses of the National Institutes of Health genetically heterogeneous rat stock (N/Nih-HS rats) in comparison with responses of the relatively high and low stress-prone Roman Low- (RLA-I) and High-Avoidance (RHA-I) rat strains. The same rats were also compared (experiment 1) with respect to their levels of unconditioned anxiety (elevated zero-maze test), novelty-induced exploratory behavior, conditioned fear and two-way active avoidance acquisition. In experiment 2, naive rats from these three strains/stocks were evaluated for "depressive-like" behavior in the forced swimming test. N/Nih-HS and RLA-I rats showed significantly higher post-stress ACTH, corticosterone and prolactin levels than RHA-I rats. N/Nih-HS rats also presented the highest context-conditioned freezing responses, extremely poor two-way avoidance acquisition and very low novelty-induced exploratory behavior. Experiment 2 showed that, compared to RHA-I rats, N/Nih-HS and RLA-I rats displayed significantly less struggling (escape-directed) and increased immobility responses in the forced swimming test. Factor analysis of data from experiment 1 showed associations among behavioral and hormonal responses, with a first factor comprising high loadings of elevated zero-maze variables and lower loadings of conditioned fear, two-way avoidance acquisition and hormonal measures, while a second factor mainly grouped conditioned fear and two-way avoidance acquisition with novelty-induced exploration and post-stress prolactin. Thus, regarding their anxiety/fearfulness, passive coping style, "depressive-like" and stress-induced hormonal responses the N/Nih-HS rats resemble the phenotype profiles of the relatively high-anxious and stress-prone RLA-I rat strain.

Body fat distribution and organ weights of 14 common strains and a 22-strain consomic panel of rats.

The goal of this study was to determine the adiposity of a range of rat strains, including a panel of consomics, to estimate heritability. To that end, we assessed the body fat distribution and organ weights of groups of adult male rats from 3 outbred strains, 11 inbred strains and 22 consomic strains. We measured the weights of the gonadal, retroperitoneal, mesenteric, femoral, subscapular and pericardial white fat depots, the subscapular brown fat depot, the kidneys, liver, heart, spleen, and brain. Strains were compared for the measured weight of each of these adipose depots and organs, and also for these weights adjusted statistically for body size. All individual adipose depot and organ weights were highly heritable, in most cases h(2)>0.50. The fourteen inbred and outbred rat strains were not very different in body length but there was a three-fold difference in body weight, and up to a twenty-fold difference in the weight of some adipose depots. Comparison of the FHH-Chr n(BN) consomic strains with the FHH host strain revealed 98 quantitative trait loci (QTLs) for body composition and organ weight, with the introgressed chromosome reducing weight or adiposity in most cases. These results can be used to guide the choice of appropriate rat strains for future studies of the genetic architecture of obesity and body size.

Superovulatory response, oocyte spontaneous activation, and embryo development in WMN/Nrs inbred rats.

WMN/Nrs inbred rats have been widely used in radiation biology for years. However, their reproductive profile has never been examined. We examined various reproductive characteristics of WMN/Nrs inbred rats such as superovulatory response, oocytes spontaneous activation (OSA), and embryo development in vitro and in vivo. Superovulation was induced in 3- to 9-week-old females by injection of 150 IU/kg PMSG and 150 IU/Kg hCG by 48 h apart. Only 8- and 9-week-old animals superovulated averaging 31.4 and 43.9 oocytes, respectively, and superovulation did not depend on estrous cycle. Animals 3-7 weeks of age did not superovulate. Because Wistar strains have been known to show a high incidence of OSA, factors expected to affect OSA in WMN/Nrs, including the time interval of various steps from euthanasia to oocyte recovery, incubation media, estrous cycle, and anesthetic treatments, were examined. The time from animal euthanasia to oviduct excision was the only factor shown to affect OSA. We also compared in vitro and in vivo embryo developmental competence between embryos obtained by natural ovulation and superovulation. Although percent in vitro development of 2-cell embryos to blastocysts was similar for embryos obtained by natural ovulation (63.7%) and superovulation (69.7%), fetus development after oviductal transfer of 2-cell embryos was significantly lower in embryos obtained by superovulation than in those obtained by natural ovulation (60.2% vs. 87.5%, P=0.02). Our results provide important normative data regarding future applications of rat assisted reproductive technologies (ARTs) such as in vitro fertilization and cryopreservation in WMN/Nrs strain and may be applicable to other strains of laboratory rats.

Differences between three inbred rat strains in number of K+ channel-immunoreactive neurons in the medullary raphé nucleus.

Ventilatory sensitivity to hypercapnia is greater in Dahl salt-sensitive (SS) rats than in Fawn Hooded hypertensive (FHH) and Brown Norway (BN) inbred rats. Since pH-sensitive potassium ion (K(+)) channels are postulated to contribute to the sensing and signaling of changes in CO(2)-H(+) in chemosensitive neurons, we tested the hypothesis that there are more pH-sensitive K(+) channel-immunoreactive (ir) neurons within the medullary raphé nuclei of the highly chemosensitive SS rats than in the other two strains. Medullary tissues from male and female BN, FHH, and SS rats were stained with cresyl violet or with antibodies targeting TASK-1, K(v)1.4, and Kir2.3 channels. K(+) channel-ir neurons were quantified and compared with the total neurons in the region. The total number of neurons in the medullary raphé 1) was greater in male FHH than the other male rats, 2) did not differ among the female rats, and 3) did not differ between sexes. The average number of K(+) channel-ir neurons per section was 30-60 neurons higher in the male SS than in the other rat strains. In contrast, for the females, the number of K(+) channel-ir neurons was greatest in the BN. We also found significant differences in the number of K(+) channel-ir neurons between sexes in SS (males > females) and BN (females > males) rats, but not the FHH strain. Our findings support the hypothesis for males but not for females, suggesting that both genetic background and sex are determinants of K(+) channel immunoreactivity of medullary raphé neurons, and that the expression of pH-sensitive K(+) channels in the medullary raphé does not correlate with the ventilatory sensitivity to hypercapnia.

Differential expression of respiratory long-term facilitation among inbred rat strains.

We tested the hypotheses that: (1) long-term facilitation (LTF) following acute intermittent hypoxia (AIH) varies among three inbred rat strains: Fischer 344 (F344), Brown Norway (BN) and Lewis rats and (2) ventral cervical spinal levels of genes important for phrenic LTF (pLTF) vary in association with pLTF magnitude. Lewis and F344, but not BN rats exhibited significant increases in phrenic and hypoglossal burst amplitude 60min post-AIH that were significantly greater than control experiments without AIH, indicating strain differences in phrenic (98%, 56% and 20%, respectively) and hypoglossal LTF (66%, 77% and 5%, respectively). Ventral spinal 5-HT(2A) receptor mRNA and protein levels were higher in F344 and Lewis versus BN, suggesting that higher 5-HT(2A) receptor levels are associated with greater pLTF. More complex relationships were found for 5-HT(7), BDNF and TrkB mRNA. BN had higher 5-HT(7) and TrkB mRNA versus F344; BN and Lewis had higher BDNF mRNA levels versus F344. Genetic variations in serotonergic function may underlie strain differences in AIH-induced pLTF.

Differential proteomics in the aging Noble rat ventral prostate.

Incidence of prostatic diseases increases dramatically with age which may be related to a decline in androgen support. However, the key mechanisms underlying prostate aging remain unclear. In the present study, we investigated the aging process in the ventral prostate (VP) of Noble rats by identifying differentially expressed prostate proteins between 3- and 16-month-old animals using ICAT and MS. In total, 472 proteins were identified with less than a 1% false positive rate, among which 34 were determined to have a greater than two-fold increase or 1.7-fold decrease in expression in the aged VPs versus their younger counterparts. The majority of the differentially expressed proteins identified have not been previously reported to be associated with prostate aging, and they fall into specific functional categories, including oxidative stress/detoxification, chaperones, protein biosynthesis, vesicle transport, and intracellular trafficking. The expression of GST, ferritin, clusterin, kininogen, oxygen regulated protein 150, spermidine synthase, ADP ribosylation factor, and cyclophilin B was verified by Western blot analyses on samples used for the ICAT study, as well as on those obtained from an independent group of animals comprised of three age groups. To the best of our knowledge, this is the first study on the proteome of the aging rat prostate.

Comparison of cortical epileptic afterdischarges in immature genetic absence epilepsy WAG/Rij rats with those in two other strains (ACI and Wistar).

The aim of this study was to examine the development of cortical epileptic afterdischarges (ADs) in genetic absence epilepsy WAG/Rij rats, and to compare them with two strains with minimal incidence of spike-and-wave (SW) episodes (ACI and Wistar). Epileptic ADs were elicited by stimulation of sensorimotor cortex in 12-, 18-, and 25-day-old rats of the three strains. The threshold current intensities were established for movements accompanying stimulation, for ADs of the SW type and accompanying clonic seizures and for transition into limbic type of ADs (characterized by behavioral automatisms). Individual groups were formed by 7-12 rats. There were no differences among the three strains in the thresholds for elicitation of stimulation-bound movements. In contrast, WAG/Rij and ACI rats exhibited easier elicitation of SW ADs than Wistar rats at the age of 18 and 25 days. There was no difference among the three strains in transition into the limbic type of ADs in 18- and 25-day-old rats. Lower thresholds for SW ADs in 18- and 25-day-old WAG/Rij and ACI rats in comparison with Wistar rats are in agreement with our data from adult animals as well as with development of pharmacologically induced models of absence seizures. The failure to find a specific difference between WAG/Rij rats and the other two strains might indicate a difference in generation of SW episodes and SW cortical AD.

Delay discounting and impulsive choice in the rat.

Delay discounting refers to the degree to which immediate outcomes exhibit more influence over behavior than outcomes which are delayed. Impulsive choice, in the context of delay discounting, is generally considered as an increased preference for immediate over delayed outcomes, even where the delayed outcomes are more advantageous. In the past decade, there has been increasing use of delay-discounting paradigms to elucidate the physiological, pharmacological, and behavioral aspects of the putative neural circuitry underlying impulsive choice. This unit describes the assessment of impulsive choice in the rat using a delay-discounting procedure involving an operant response choice between a small reinforcer delivered immediately and a larger reinforcer delivered after a delay, which is progressively increased within a session. Variations of some of the main task parameters are also discussed, as well as their significance and interpretation.

Postnatal developmental changes in CO2 sensitivity in rats.

Ventilatory sensitivity to CO(2) in awake adult Brown Norway (BN) rats is 50-75% lower than in adult Sprague-Dawley (SD) and salt-sensitive Dahl S (SS) rats. The purpose of the present study was to test the hypothesis that this difference would be apparent during the development of CO(2) sensitivity. Four litters of each strain were divided into four groups such that rats were exposed to 7% inspired CO(2) for 5 min in a plethysmograph every third day from postnatal day (P) 0 to P21 and again on P29 and P30. From P0 to P14, CO(2) exposure increased pulmonary ventilation (Ve) by 25-50% in the BN and SD strains and between 25 to over 200% in the SS strain. In all strains beginning around P15, the response to CO(2) increased progressively reaching a peak at P19-21 when Ve during hypercapnia was 175-225% above eucapnia. There were minimal changes in CO(2) sensitivity between P21 and P30, and at both ages there were minimal between-strain differences. At P30, the response to CO(2) in the SS and SD strains was near the adult response, but the response in the BN rats was 100% greater at P30 than in adults. We conclude that 1) CO(2)-sensing mechanisms, and/or mechanisms downstream from the chemoreceptors, change dramatically at the age in rats when other physiological systems are also maturing ( approximately P15), and 2) there is a high degree of age-dependent plasticity in CO(2) sensitivity in rats, which differs between strains.

Competition for sucrose pellets in tetrads of male Wistar, Fischer or Sprague-Dawley rats: is intra-group ranking reflected in the level of anxiety?

Competition for palatable food or fluids within groups of rats has been previously used to mirror intra-group ranking. The paradigm of competition for sucrose pellets in non-food-deprived male Wistar rats was here extended from triads to tetrads aiming at evaluating whether the number of poor-performing rats, those animals being likely to model aspects of human psychopathologies (anxiety/depression/social withdrawal), could be increased. To evaluate potential superiority over the previously used Wistar strain, establishment and stability of the ranking was also assessed in tetrads of male Fischer and Sprague-Dawley rats. Clear and stable rank orders were seen in around 60-70% of both triads and tetrads of Wistar rats: a high-performing, a medium-performing and one (in triads) or two (in tetrads) poor-performing rats were identifiable, indicating that the number of poor-performing rats had increased in tetrads. Comparable rank orders were also seen in tetrads of Fischer and Sprague-Dawley rats. At the end of an extended period of repeated testing, tetrads of these two strains, as well as some selected Wistar tetrads, were tested in the elevated zero-maze and plasma corticosterone levels were determined. The differentiation in competition-performance among cage mates was not paralleled by a difference in performance in the elevated zero-maze or in plasma corticosterone levels in any of the three strains. These data indicate that the level of anxiety in a non-social paradigm, the elevated zero-maze, does not reflect the competition-performance within the home cage and thus, the dominant/subordinate status in this food-competition paradigm may not reflect/being caused by different levels of anxiety.