Exploration In Rats Research Articles

Long-term consumption of rooibos herbal tea affects hypothalamic neurotransmission and social behavior of adult Sprague–Dawley male rats

Abundant in phenolic compounds, “fermented” rooibos herbal tea (FRHT) improves the cognitive performance and exploration of rats, as well as alters the content of monoamines and amino acids in some brain structures. Here, we aim to extend knowledge about the neurochemical and behavioral outcomes of long-term oral FRHT consumption by examining its impact on hypothalamus functions. FRHTs of different leaf-to-water ratios were given to adult male SD rats for 3 months. Their behavior was evaluated in social interaction test. The concentration of hypothalamic monoamines and amino acids was analyzed by HPLC-ECD whereas BDNF/TrkB by Elisa method. It was shown that sustained FRHT consumption did not affect aggression of the rats but was able to increase social deficits, expressed as diminished total time of contact and shorter active social interaction. Upon biochemical investigation, the changes were primarily linked to serotonergic, glutaminergic, and BDNF/TrkB pathway. Decreased 5-HT and TrkB content in the hypothalamus could be linked with social deficits and suggested positive effect on central energy balance, yet the main body mass of animals in the experiment remained unaffected. On the other hand, the reduced hypothalamic serotonin signaling anticipated the influence on hypothalamic–pituitary–adrenal axis and possible diminution of plasma corticosterone level with subsequent behavioral aftermath and lower obesity risk. Our research contributes toward better understanding of the mechanism of action of rooibos tea and its effects within the central nervous system.Graphical abstract

Animals in Search of Stimulation and Information: A Review of over 10 years of our Research on Spontaneous Exploration in Rats as a Response to Novelty in Low-Stress Paradigm

This article comprehensively reviews our studies that analyzed novelty-related behaviors in rats. We developed and utilized techniques and equipment during these studies to ensure our findings' high ecological validity. We allowed rats to explore a testing apparatus freely, and after a long habituation phase consisting of multiple trials, we introduced non-emotionally arousing changes. The research shows that rats demonstrate enhanced abilities in processing and responding to heightened environmental complexity, as evidenced across various studies. Conversely, when environmental complexity diminishes, rats exhibit reduced exploratory behaviors and decreased cognitive effort despite the adaptive importance of such behaviors. Of particular interest is the observation that rats exhibit greater sensitivity to emerging opportunities in contrast to their limited responsiveness to diminishing ones, unveiling a novel facet of the animal mind that warrants further investigation. The influence of individual experiences before testing sessions on the processing of sensory input in terms of complexity is also determined. Our studies highlight the noteworthy impact of environmental unpredictability versus stability on cognitive development, affecting behaviors like food neophobia and exploration. Furthermore, the social environment during development holds wide-ranging implications for individual characteristics, necessitating continued research and refinement of our understanding in this domain. Moreover, the studies recognize strain and species differences in novelty-related behavior, primarily characterized by quantitative variations that do not overshadow the animals' coping strategies in response to environmental changes. Additionally, curiosity is portrayed as an active approach to seeking and processing environmental affordances, with exploratory behaviors fulfilling this cognitive and motivational need. The authors underscore the significance of ecological validity in test methodologies, particularly in designing environments that authentically invite and encourage pertinent behavioral responses. In summary, this research enhances our insight into rat cognition, underscores the role of curiosity, and underscores the imperative of ecological validity in experimental design, ultimately advancing our comprehension of animal behavior and cognition.

Exploring the Molecular and Genetic Mechanisms of Action of the α2-Adrenergic Agonist Mafedine in Experimental Traumatic Brain Injury in Rats

Neurological impairments due to traumatic, vascular, or neurodegenerative brain diseases have a high prevalence worldwide. Among them are motor, cognitive, and mental disorders, which have a serious negative impact on the working and social activities of the patients. This calls for the search and development of novel effective neuroprotective agents. Previous studies have shown the pyrimidine-derived α2-adrenergic agonist mafedine to be highly effective for the amelioration of neurological deficits in experimental traumatic brain injury (TBI) in rats. Despite the results of the previous works favouring the major role of the α2 adrenergic receptor activation in the mechanism of action of mafedine, the search for additional molecular targets is an important part of the development of any drug to be used in clinical practice. In this work, we evaluated the effects of 7 day-long course administration of mafedine (2.5 mg/kg b.w.) on the expression of brain-derived neurotrophic factor (BDNF), the proinflammatory cytokines interleukin (IL)-1β, -6, tumour necrosis factor (TNF)-α, and the α2A, α2B, and α2C α2-adrenergic receptor subtypes in the brain cortex of rats subjected to TBI, using the reverse-transcription real-time polymerase chain reaction method. TBI was modelled by the controlled cortical impact technique in an open area of sensorimotor cortex of the left brain hemisphere. Behavioural alterations in the injured animals were assessed in the Open field test, and the fore- and hindlimb motor function, in the Limb placing, Cylinder, and Beam walking tests. Our experiments show that TBI causes severe motor impairments as well as decreases exploration in rats. Besides, at post-TBI day 7, a reduction in the expression of all analyzed genes is seen, which is the most pronounced in the contralateral (uninjured) hemisphere. Course administration of mafedine (2.5 mg/kg b.w.) resulted in moderate stimulation of the injured rats’ behaviour, increased exploratory activity compared to controls, and improved sensorimotor deficit as assessed by the Beam walking test. Gene expression analysis results indicated that mafedine decreased α2B-adrenergic receptor, TNF-α, and IL-6 expression in the injured hemisphere. At the same time, compared to rats with TBI having received no treatment, mafedine-treated animals exhibited higher α2B-adrenergic receptor and IL-1β expression in the injured rather than the intact hemisphere. These results confirm the previously observed neuroprotective activity of mafedine and imply that it may exert its effects via suppression of α2B-adrenergic receptor and proinflammatory cytokine expression in the injured brain hemisphere, at the same time increasing their expression in the intact one.

Protocol for Measuring Free (Low-stress) Exploration in Rats.

Research on exploratory behavior plays a key part in behavioral science. Studying exploratory behavior of laboratory rodents may provide important data about many developmental and neurobiological processes occurring in animal ontogenesis. The proposed protocol for measuring the free (low-stress) exploration behavior in rats is straightforward, requires minimal resources and very little animal training. It can therefore be broadly applied to studying animal cognition, animal behavior in general, the aging processes, and several animal models of various phenomena.

Serotonin transporter deficiency alters socioemotional ultrasonic communication in rats

It has been widely established that serotonin plays important role in the regulation of emotional and social behaviour. Rodents with a genetic deletion of the serotonin reuptake transporter (SERT) are used as a model to study lifelong consequences of increased extracellular 5‐HT levels due to its impaired reuptake. SERT knock-out (SERT-KO) mice and rats consistently showed anxiety-like symptoms and social deficits. Nevertheless, the impact of SERT deletion on socioemotional ultrasonic communication has not been addressed. Here we investigated the impact of lifelong serotonin abundance on ultrasonic vocalisation accompanying social interactions and open field exploration in rats. SERT-KO rats displayed reduced overall duration of social contacts, but increased time spent on following the conspecific. The altered pattern of social behaviour in SERT-KO rats was accompanied by the structural changes in ultrasonic vocalisations, as they differed from their controls in distribution of call categories. Moreover, SERT deletion resulted in anxiety-like behaviours assessed in the open field test. Their anxious phenotype resulted in a lower tendency to emit appetitive 50-kHz calls during novelty exploration. The present study demonstrates that genetic deletion of SERT not only leads to the deficits in social interaction and increased anxiety but also affects ultrasonic communication.

The impact of changeability of enriched environment on exploration in rats

Although the positive effect of environmental enrichment on animals’ cognitive capacities is well-known, it remains unclear what role changeability plays in this context. Our study aims to analyse the impact of environmental changeability on the level of exploration and the rate of habituation to novelty.Prior to the experiment, the animals were housed in three settings: enriched stable conditions, enriched changing conditions and standard conditions. Environmental changeability was introduced by re-arranging objects in the housing pen. A test was conducted to measure the level of exploration in adult individuals.The study results suggest that rats housed in standard conditions exhibit a higher demand for interactions with the new environment. However, once novelty is introduced, rats from the enriched environments spend more time than their standard counterparts exploring the new objects. No significant differences have been observed in the behaviour of rats from the stable and changeable conditions. It may be concluded, therefore, that in a setting characterised by long-lasting environmental enrichment, the changeability of the environment plays no major role, at least with respect to exploration, general activity and the rate of habituation to novelty. It may be linked to the relatively quick extinguishment of behaviours reinforced by intrinsic reinforcement.

Early paracetamol exposure decreases brain-derived neurotrophic factor (BDNF) in striatum and affects social behaviour and exploration in rats

The biochemical and behavioral responses to prenatal and early postnatal exposure to paracetamol in rats are not well understood. The effect of daily maternal and early life administration of 5 mg/kg (group P5) or 15 mg/kg paracetamol (group P15) was evaluated in two-month old male rats, relative to control animals receiving tap water (Con). Social behavior and episodic memory were investigated with Social Interaction and Novel Object Recognition (NOR) tests. Quantification of brain-derived neurotrophic factor (BDNF) was determined in prefrontal cortex, hippocampus and striatum using enzyme-linked immunosorbent assay (ELISA).Control animals exhibited a higher total frequency of social interactions and greater frequency of sniffing compared to rats exposed to paracetamol, and we found a statistically significant increase in the occurrence of pinning in paracetamol-treated animals. Rats from the 15 mg/kg group exhibited a greater interest in objects in the NOR test and spent more time exploring objects during the familiarization and choice phases. Biochemical analysis showed significant differences in striatal BDNF between the groups, specifically, a nearly two-fold decrease in striatal BDNF in the paracetamol groups (P5: 6.78 ± 0.60 pg/mg; P15: 6.06 ± 0.46 pg/mg) relative to the control group (Con: 11.33 ± 2.00 pg/mg). These results indicate that paracetamol exposure induces changes in social behaviour and exploration in rats and results in a significant decrease of striatal BDNF.

Inhibiting medial septal cholinergic neurons with DREADD alleviated anxiety-like behaviors in mice

Cholinergic neurons in the medial septum (MS) participate in a variety of cognitive and emotional behaviors. Some studies but not others show that lesions or inhibition of the MS reduce anxiety-like behaviors and locomotive exploration in rats. However, these conclusions come from manipulations that are either irreversible or non-specific to cholinergic neurons, casting doubt on their validity. With DREADD (designer receptors exclusively activated by designer drugs), we temporarily and reversibly inhibited cholinergic neurons in the MS. We observed consistent anxiolytic effects of MS cholinergic inhibition in the novelty-suppressed feeding test, the marble burying test and the elevated plus-maze test, as well as increased exploratory activities in the open field test. These findings confirm an excitatory role of the MS cholinergic neurons in the control of innate anxiety, and reconcile conflicting findings from previous studies using irreversible lesions or non-specific inhibition.

In vitro and in vivo characterisation of Lu AF64280, a novel, brain penetrant phosphodiesterase (PDE) 2A inhibitor: potential relevance to cognitive deficits in schizophrenia

Here, we present the pharmacological characterisation of Lu AF64280, a novel, selective, brain penetrant phosphodiesterase (PDE) 2A inhibitor, in in vitro/in vivo assays indicative of PDE2A inhibition, and in vivo models/assays relevant to cognitive processing or antipsychotic-like activity. The in vitro selectivity of Lu AF64280 was determined against a panel of PDE enzymes and 3',5'-cyclic guanosine monophosphate (cGMP) levels in the hippocampus were determined using in vivo microdialysis. Lu AF64280 potently inhibited hPDE2A (Ki = 20 nM), 50-fold above moderate inhibition of both hPDE9A (Ki = 1,000 nM) and hPDE10A (Ki = 1,800 nM), and displayed a >250-fold selectivity over all other full-length human recombinant PDE family members (Ki above 5,000 nM). Lu AF64280 (20 mg/kg) significantly increased cGMP levels in the hippocampus (p < 0.01 versus vehicle-treated mice), attenuated sub-chronic phencyclidine-induced deficits in novel object exploration in rats (10 mg/kg, p < 0.001 versus vehicle-treated), blocked early postnatal phencyclidine-induced deficits in the intradimensional/extradimensional shift task in rats (1 and 10 mg/kg, p < 0.001 versus vehicle-treated) and attenuated spontaneous P20-N40 auditory gating deficits in DBA/2 mice (20 mg/kg, p < 0.05 versus vehicle-treated). In contrast, Lu AF64280 failed to attenuate phencyclidine-induced hyperactivity in mice, and was devoid of antipsychotic-like activity in the conditioned avoidance response paradigm in rats, at any dose tested. Lu AF64280 represents a novel tool compound for selective PDE2A inhibition that substantiates a critical role of this enzyme in cognitive processes under normal and pathological conditions.

Sustained transcription of the immediate early gene Arc in the dentate gyrus after spatial exploration.

After spatial exploration in rats, Arc mRNA is expressed in ∼2% of dentate gyrus (DG) granule cells, and this proportion of Arc-positive neurons remains stable for ∼8 h. This long-term presence of Arc mRNA following behavior is not observed in hippocampal CA1 pyramidal cells. We report here that in rats ∼50% of granule cells with cytoplasmic Arc mRNA, induced some hours previously during exploration, also show Arc expression in the nucleus. This suggests that recent transcription can occur long after the exploration behavior that elicited it. To confirm that the delayed nuclear Arc expression was indeed recent transcription, Actinomycin D was administered immediately after exploration. This treatment resulted in inhibition of recent Arc expression both when evaluated shortly after exploratory behavior as well as after longer time intervals. Together, these data demonstrate a unique kinetic profile for Arc transcription in hippocampal granule neurons following behavior that is not observed in other cell types. Among a number of possibilities, this sustained transcription may provide a mechanism that ensures that the synaptic connection weights in the sparse population of granule cells recruited during a given behavioral event are able to be modified.

Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia, phosphorylation of NMDA receptors, and cytokines expression in the thoracic spinal dorsal horn

BackgroundWe previously reported that immune activation in the spinal dorsal horn contributes to pain induced by chronic pancreatitis (CP). Targeting immune response in the CNS may provide effective treatments for CP-induced pain. Recent findings demonstrate that resolvin D1 (RvD1) can potently dampen inflammatory pain. We hypothesized that intrathecal injection of RvD1 may inhibit pain of CP.MethodsRat CP model was built through intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). All the rats were divided into three groups: TNBS, sham, and naïve controls and were further divided for intrathecal RvD1 administration. Pain behavior of rats was tested with von Frey filaments. Anxiety-like behavior and free locomotor and exploration of rats were evaluated by open field test and elevated plus maze. Pancreatic histology was evaluated with hematoxylin and eosin staining. Phosphorylation of NMDA receptor and expression of inflammatory cytokines were examined with Western blot, real-time RT-PCR and ELISA.ResultsBehavioral study indicated that compared to the vehicle control, RvD1 (100 ng/kg) significantly decreased TNBS-induced mechanical allodynia at 2 h after administration (response frequencies: 49.2 ± 3.7% vs 71.3 ± 6.1%), and this effect was dose-dependent. Neither CP nor RvD1 treatment could affect anxiety-like behavior. CP or RvD1 treatment could not affect free locomotor and exploration of rats. Western blot analysis showed that compared with that of naïve group, phosphorylated NR1 (pNR1) and pNR2B in TNBS rats were significantly increased in the spinal cord (pNR1: 3.87±0.31 folds of naïve control, pNR2B: 4.17 ± 0.24 folds of naïve control). Compared to vehicle control, 10 ng/kg of RvD1 could significantly block expressions of pNR1 (2.21 ± 0.26 folds of naïve) and pNR2B (3.31 ± 0.34 folds of naïve). Real-time RT-PCR and ELISA data showed that RvD1 (10 ng/kg) but not vehicle could significantly block expressions of TNF-alpha, IL-1beta and IL-6. In addition, RvD1 did not influence pain behavior, NMDA receptor phosphorylation or cytokines production in sham-operated rats.ConclusionsThese data highly suggest that RvD1 could be a novel and effective treatment for CP-induced chronic pain.

Memory traces compete under regimes of limited Arc protein synthesis: Implications for memory interference

Recently encoded information can be lost in the presence of new information, a process called ‘retrograde interference’. Retrograde interference has been extensively described for more than a century; however, little is known about its underlying mechanisms. Different approaches agree on the need of the synthesis of plasticity related proteins (PRPs) to consolidate a long-term memory (LTM). Our hypothesis is that when PRPs are limited, interference of a task over LTM formation of another may be due to the utilization of protein resources common to both tasks. Here, by combining the tasks of inhibitory avoidance (IA) and open field (OF) exploration in rats, we show that memory traces compete for their stabilization if PRPs are limited. As a result, LTM is formed for only one of the tasks with a consequent decrease in the memory for the other. Furthermore, infusing Arc antisense oligonucleotide into the dorsal hippocampus, we found that Arc is necessary for LTM formation of these two types of learning tasks and is one of the PRPs that can be shared between them when animals are trained in both OF and IA. In sum, these findings suggest that under conditions of reduced protein availability, a learning task interferes with LTM formation of another by using the available PRPs.

Response to spatial and nonspatial change in wild (WWCPS) and Wistar rats

Response to spatial and nonspatial change in wild (WWCPS) and Wistar rats The purpose of the experiment was to investigate the effects of domestication on exploration in rats. The comparison was made between wild Warsaw-Wild-Captive-Pisula-Stryjek (WWCPS) rats and Wistar laboratory rats. The study used a purpose-built maze divided into zones connected with a corridor. Objects were placed in two out of four zones. Their location and shape were subject to experimental manipulation. Transporter used to move rats to the maze provided the opportunity for spontaneous exploration of the experimental arena. Rats were subjected to a series of 10 sessions (habituation), followed by a spatial or nonspatial change in the experimental arena, after which another 5 experimental sessions were conducted. The study revealed that wild rats had much higher exploration latency than their laboratory counterparts. At each analyzed stage, WWCPS rats spent much more time in the transporter than Wistar rats. Wistar rats spent much more time during the experiment on object interaction in the experimental arena. In post-manipulation sessions, however, it was wild rats that explored object zones relatively longer than laboratory rats. No differences in the animals' behavior depending on the type of change were observed. Results suggest that wild rats tend to explore much more cautiously than laboratory rats and are more sensitive to changes in their environment. The underlying cause of these differences is likely to be the higher level of stress in wild rats, resulting from threats in their natural habitat.

Effects of melanotan II, a melanocortin agonist, on grooming and exploration in rats after repeated restraint/immobilization

2mg/kg melanotan II (MTII, administered i.p.), a cyclic peptide analog of alpha-melanocyte stimulating hormone, at a single dose increased grooming in naive rats placed in an unfamiliar open-field device without changing locomotion or rearing. Male rats exposed to restraint/immobilization stress (IS) for 1h on three consecutive days displayed increased grooming after the second stressor exposure, compared to pre-stress levels. MTII, administered to the rats after IS, enhanced the grooming response compared both to the pre- and post-stress values. The increase was greatest after the first dose and declined over the following two applications. As to the locomotion of rats in the entire experimental space, IS reduced the distance moved only after the first two stressor exposures; MTII did not influence these alterations. Locomotion in the central part of arena was not reduced by the stressor or by MTII, on the contrary, there was an increase in both groups after the third intervention. The only observed change in rearing was an increase in the MTII group after the third restraint exposure. Thus, MTII selectively increased grooming without markedly affecting the spatio-temporal structure of locomotor behavior in the open-field. The decline of MTII enhanced grooming over the three test days may be interpreted in terms of adaptation to the stressor and of the developing tolerance to the peptide.

Positional Cloning of Quantitative Trait Loci for Blood Pressure: How Close Are We?

Blood pressure (BP) in any human population exhibits as a continuous variable that fits a bell-shaped curve. Hypertensive individuals are those whose BP is maintained at one extreme of the curve and above a defined cutoff. Despite progress made in identifying the mechanisms underlying certain rare monogenic forms of hypertension,1,2 the etiology and pathogenesis of essential hypertension remain poorly understood. Because existing human populations are genetically heterogeneous, and because environmental factors impacting on the pathogenesis of hypertension cannot be controlled in a given population, it is difficult to identify the molecular mechanisms that transduce the sequela of essential hypertension via direct human studies.3 To alleviate the drawbacks of human investigations, animal models, especially inbred rodents, have been developed and experimentally manipulated to identify quantitative trait loci (QTLs) for BP, because major confounding environmental factors, such as diet and genetic background, can be systematically controlled. Once identified in animal models, the molecular basis may be translated into physiological understandings of essential hypertension in humans. It is with this expectation that efforts have been launched to identify the molecular basis of BP QTLs in animal models. Because the identification of individual QTLs is primarily based on their chromosome locations unbiased by, or unrestricted to, their physiological roles, positional cloning is believed to be the most efficient strategy. Before we embark on discussions regarding QTL discovery, a definition is in order. Semantic arguments abound as to exactly what a QTL, that is, a locus,4 entails. Is it 1 gene or a collection of genes? As genetic mapping progresses from a large chromosome segment to an interval of submegabase, several regions initially thought to contain 1 BP QTL5 appear to harbor >1 in each of them,6–10 whereas several other regions turned out to harbor 1 QTL as expected.11,12 …

Medial prefrontal cortex is involved in spatial temporal order memory but not spatial recognition memory in tests relying on spontaneous exploration in rats

The present study describes two novel tasks relying on spontaneous patterns of exploration in a radial-arm maze that can be used to assess spatial recognition memory and spatial temporal order memory (i.e. memory for the order in which places have been visited) in the rat. In the recognition memory task, rats were permitted to freely explore two arms in the maze on a first trial and one ‘familiar’ arm and one novelly located arm on a second trial 105 min later. In the temporal order memory task, rats were permitted to explore two arms in the maze on a first trial, two novel arms on a second trial 60 min later, and one ‘older familiar’ arm and one ‘more recent familiar’ arm on a third trial 45 min later. Using these tasks, we found that rats direct greater exploration at a novel than a familiar arm location, thus showing long-term spatial recognition memory, and at an older familiar arm than a more recent familiar arm, thus showing long-term spatial temporal order memory. Lidocaine inactivation of the mPFC prior to the final trial in each task disrupted performance on the temporal order but not the recognition memory task, thereby demonstrating a role for the mPFC in the retrieval and/or use of temporal order information but not in spatial memory per se. These findings highlight the specific involvement of the rat mPFC in temporal order memory and have important implications for a broader understanding of mPFC function.

The effect of social factors on the anxiolytic efficacy of buspirone in male rats, male mice, and men

Earlier findings suggest that housing conditions in laboratory animals and life events in humans influence the efficacy of anxiolytic drugs. Here we report on the impact of social isolation on buspirone efficacy in male mice and rats as assessed by the elevated plus-maze. In addition, the impact of social support on buspirone efficacy was assessed in male patients. When administered 30 min before testing and irrespective of housing conditions, buspirone significantly suppressed locomotor activity both in mice (6 mg/kg) and rats (10 mg/kg) and, as such, other behavioral changes observed at this time point must be seen as behaviorally nonselective. However, these locomotor disruptive effects of buspirone were not evident in either species at longer injection-test intervals (2 and 4 h). When given 2 h prior to testing, a low (3 mg/kg) but not high (10 mg/kg) dose of buspirone increased the frequency of open arm exploration in rats (but not mice) irrespective of housing conditions. At the longest injection-test interval used (4 h), buspirone increased the duration of open arm exploration in individually housed, but not group-housed, rats. Similar, though somewhat less robust, effects were observed in male mice at this time. In a double-blind placebo-controlled study with male patients, chronic buspirone treatment (3×10 mg daily for 6 weeks) produced a highly significant reduction in scores on the Hamilton Rating Scale for Anxiety (HAM-A). Multiple regression analysis of social support received by patients indicated that the support of nonrelatives (but not of family or other relatives) was a strong positive predictor of buspirone efficacy. Taken together, our data support the hypothesis that social conditions affect the anxiolytic efficacy of buspirone. Results are discussed in relation to differences in the social organization of the three species investigated.

Fimbria-fornix lesions disrupt the dead reckoning (homing) component of exploratory behavior in mice.

Exploration is the primary way in which rodents gather information about their spatial surroundings. Thus, spatial theories propose that damage to the hippocampus, a structure thought to play a fundamental role in spatial behavior, should disrupt exploration. Exploration in rats is organized. The animals create home bases that are central to exploratory excursions and returns, and hippocampal formation damage alters the organization of exploration by disrupting returns. Mice do not appear to readily establish home bases in novel environments, thus, for this species, it is more difficult to establish the contribution of the hippocampus to exploration. The purpose of the present study was threefold: develop a task in which mice center their exploration from a home base, determine whether the exploratory behavior is organized, and evaluate the role of fimbria-fornix lesions on exploration. Mice were given a novel exploratory task in which their nesting material was placed on a large circular table. Video records of control and fimbria-fornix mice were made in both light and dark (infrared light) conditions. Exploration patterns (outward trips, stops, and homeward trips) were reconstructed from the video records. Control mice centered their activity on their bedding, from which they made circuitous outward trips marked by many stops, and periodic direct returns. The bedding-centered behavior and outward trips of the fimbria-fornix mice were similar to those of the control mice, but significantly fewer direct return trips occurred. The direct homeward trips observed under light and dark conditions were consistent with a dead-reckoning strategy, in which an animal computes its present position and homeward trajectory from self-movement cues generated on the outward trip. Because the fimbria-fornix lesions disrupted the homeward component of exploratory trips, we conclude that the fimbria-fornix may contribute to dead reckoning in mice. The results also show that the home-bedding methodology facilitates the establishment of a home base by mice, thus providing a useful methodology for studies with mice.

Enrichment-dependent differences in novelty exploration in rats can be explained by habituation

In rats, exploratory activity and emotional reactivity towards novel stimuli reflect independent biological functions that are modulated differently by rearing experiences. Environmental enrichment is known to improve performance in exploratory tasks, while having inconsistent effects on emotionality. This study examined the effect of environmental enrichment on the behaviour of rats in two exploratory tasks. Male rats were reared under one of four conditions, differing in social and non-social complexity. At 9 weeks of age, exploration of a novel open field, and exploration of novel objects in the same open field following 24 h habituation, was assessed. Differences in social and non-social complexity of the rearing environment had inconsistent effects on exploration in the novel open field. In contrast, when rats were faced with novel objects in an otherwise familiar environment, exploration habituated faster with increasing stimulus complexity of the non-social environment. The social environment had no effect on this latter test. These findings indicate that environmental enrichment affects exploratory activity primarily through its effect on habituation to novelty. This effect depends on relative stimulus complexity of the rearing environment, but is independent of social factors. The present results further suggest that aversive tasks can obscure the expression of enrichment-dependent differences in habituation to novelty.

Vagotomy attenuates the behavioural but not the pyrogenic effects of interleukin-1 in rats

Vagal afferent signals, have been implicated in cytokine mediated interactions between the periphery and the central nervous system. Studies in experimental animals have shown that cytokine induced activation of brain mediated responses to infection such as fever, sickness behaviour and pituitary-adrenal activation, are inhibited by subdiaphragmatic vagotomy. We have previously proposed that the peripheral signal to the brain in fever is of a humoral nature while others have suggested that either neural afferents or a mixture of both humoral and neural signals may be involved. The objective of the present study was to examine further the role of vagal transmission, in mediating the febrile response to a systemic injection of IL-1β in rats and to compare this with changes in social exploration behaviour. Intraperitoneal injection of IL-1β (1.0–30.0 μg/kg) inhibited social exploration in rats and this was attenuated in vagotomized animals. Injection of increasing concentrations of IL-1β (0.1–1.0 μg/rat) induced significant ( P<0.001) increases in core body temperature. However, in contrast to effects on social exploration, the increase in temperature was not inhibited by vagotomy at any of the doses used. These observations demonstrate a dissociation between the two brain mediated events, one of which is dependent on the integrity of the vagus nerve (social exploration) while the other (fever) is apparently generated by different mechanisms which may include circulating pyrogens.