Anxiety-related behaviors in mice are often assessed over short periods starting immediately after introducing the animals in a dedicated apparatus. In these usual conditions (5-10 min periods), the cerebellar Lurcher mutants showed disinhibited behaviors characterized by abnormally high exploration of the aversive areas in the elevated plus-maze test. We nevertheless observed that this disinhibition sharply weakened after 10 min. We therefore decided to further investigate the influence of the disinhibition on the intrinsic and anxiety-related exploratory behaviors in Lurcher mice, with a special focus on familiarization effects. To this end, we used an innovative apparatus, the Dual Maze, permitting to tune the familiarization level of animals to the experimental context before they are faced with more (open configuration of the device) or less (closed configuration of the device) aversive areas. Chlordiazepoxide administration in BALB/c mice in a preliminary experiment confirmed both the face and the predictive validity of our device as anxiety test and its ability to measure exploratory motivation. The results obtained with the Lurcher mice in the open configuration revealed that 20 min of familiarization to the experimental context abolished the behavioral abnormalities they exhibited when not familiarized with it. In addition, their exploratory motivation, as measured in the closed configuration, was comparable to that of their non-mutant littermates, whatever the level of familiarization applied. Exemplifying the interest of this innovative device, the results we obtained in the Lurcher mutants permitted to differentiate between the roles played by the cerebellum in exploratory motivation and stress-related behaviors.
- MeSH
- Maze Learning physiology MeSH
- Behavior, Animal physiology MeSH
- Inhibition, Psychological * MeSH
- Motivation physiology MeSH
- Cerebellum MeSH
- Mice, Neurologic Mutants MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Neuropsychological Tests * MeSH
- Exploratory Behavior physiology MeSH
- Recognition, Psychology physiology MeSH
- Anxiety physiopathology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Background: Approach system considered a motivational system that activates reward-seeking behavior is associated with exploration/impulsivity, whereas avoidance system considered an attentional system that promotes inhibition of appetitive responses is associated with active overt withdrawal. Approach and avoidance dispositions are modulated by distinct neurochemical profiles and synaptic patterns. However, the precise working of neurons and trafficking of molecules in the brain activity predisposing to approach and avoidance are yet unclear. Methods: In 3 phenotypes of inbred mice, avoiding, balancing, and approaching mice, selected by using the Approach/Avoidance Y-maze, we analyzed endogenous brain levels of brain derived neurotrophic factor, one of the main secretory proteins with pleiotropic action. To verify the effects of the acute increase of brain derived neurotrophic factor, balancing and avoiding mice were bilaterally brain derived neurotrophic factor-infused in the cortical cerebellar regions. Results: Approaching animals showed high levels of explorative behavior and response to novelty and exhibited higher brain derived neurotrophic factor levels in the cerebellar structures in comparison to the other 2 phenotypes of mice. Interestingly, brain derived neurotrophic factor-infused balancing and avoiding mice significantly increased their explorative behavior and response to novelty. Conclusions: Cerebellar brain derived neurotrophic factor may play a role in explorative and novelty-seeking responses that sustain the approach predisposition.
- MeSH
- Behavior, Animal drug effects physiology MeSH
- Brain drug effects metabolism MeSH
- Brain-Derived Neurotrophic Factor metabolism pharmacology physiology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Exploratory Behavior drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Despite the encountering of a predator always being extremely threatening, there is a significant plasticity among individuals in how they cope with such a situation. In laboratory experiments with wild-caught great tits (Parus major), we tested the effect of exploratory behaviour (performance in novel food, object and environment test, startle test) on the ability of individual birds to assess the threat represented by a predator. We presented a wooden dummy of the European sparrowhawk (Accipiter nisus), an extremely dangerous predator, and its visual modifications (chimeras), changing the beak or head to be non-threatening (those of a pigeon - Columba livia f. domestica). We showed that the differences between 'slow' and 'fast explorers' are not very distinct, but that 'slow explorers' generally tended to be more cautious in the presence of an unmodified sparrowhawk dummy, while the 'fast explorers' tended to observe the dummy. On the contrary, 'slow explorers' tended to treat both chimaeras (and the pigeon dummy as well) as less-threatening than 'fast explorers'. Since 'slow explorers' are usually considered to be more sensitive to environmental cues, it came as no surprise that most of them correctly assessed the unmodified sparrowhawk dummy as threatening, while they probably subjected the chimeras to a detailed inspection and were not confused by the presence of sparrowhawk features and assessed them as non-threatening.
- MeSH
- Behavior, Animal physiology MeSH
- Passeriformes physiology MeSH
- Exploratory Behavior physiology MeSH
- Cues * MeSH
- Visual Perception physiology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Magnetosensitivity is widespread among animals with rodents being the most intensively studied mammalian group. The available behavioural assays for magnetoreception are time-consuming, which impedes screens for treatment effects that could characterize the enigmatic magnetoreceptors. Here, we present a fast and simple approach to test if an animal responds to magnetic stimuli: the magnetic object assay (MOA). The MOA focuses on investigating an animal's spontaneous exploration behaviour in the presence of a bar magnet compared to a demagnetised control. We present consistently longer exploration of the magnet in three different rodent species: Ansell's mole-rat (Fukomys anselli), C57BL/6J laboratory mouse, and naked mole-rat (Heterocephalus glaber). For the naked mole-rat this is the first report that this species reacts on magnetic stimuli. We conclude that the MOA holds the potential to screen if an animal responds to magnetic stimuli, indicating the possession of a magnetic sense.
- MeSH
- Behavior, Animal physiology MeSH
- Rodentia physiology MeSH
- Magnetic Fields * MeSH
- Mole Rats MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Exploratory Behavior physiology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The hippocampus and retrosplenial cortex are integrated within a higher-order cognitive circuit supporting relational (spatial, contextual, episodic) forms of learning and memory. Hippocampal place cells can coordinate multiple parallel representations in the same physical environment. Novel environment exploration triggers expression of immediate-early genes (IEGs) Arc and Homer1a in spatial context-specific ensembles of CA1 and CA3 neurons. Less is know about ensemble coding in the retrosplenial cortex (RSC), a region directly connected and functionally coupled to CA1. Hippocampal and retrosplenial damage is found in patients with schizophrenia alongside cognitive deficits affecting relational memory. Systemic administration of non-competitive NMDAR antagonists such as MK-801 is used to model psychosis in animals and humans. Acute systemic MK-801 (0.15 mg/kg) impaired cognitive control in rats and ensemble code for spatial context in CA1. Here, we use expression of immediate-early genes Arc and Homer 1a to examine ensemble coding in rat CA3 and RSC to test if the effect of MK-801 extends upstream and downstream of CA1, respectively. Different rats explored the same context twice (A/A), explored two distinct contexts (A/B) or remained in their home cage (CC). In contrast to CA1, MK-801 did not affect ensemble coding in CA3. Unlike CA3 and CA1, similarity of RSC ensembles active during exploration did not reflect change in spatial context, but MK-801 (0.15 mg/kg) increased similarity in RSC ensembles active during spontaneous behavior in the home cage. The data provide support for MK-801-induced functional uncoupling between CA3 and CA1 and suggest that ensemble coding deficit may extend downstream of CA1. This deficit may reflect hyperassociative state in the cognitive circuit underlying cognitive disorganization in psychosis. © 2016 Wiley Periodicals, Inc.
- MeSH
- Excitatory Amino Acid Antagonists pharmacology MeSH
- Housing, Animal MeSH
- Cytoskeletal Proteins metabolism MeSH
- Dizocilpine Maleate pharmacology MeSH
- Gene Expression drug effects MeSH
- CA1 Region, Hippocampal drug effects metabolism MeSH
- CA3 Region, Hippocampal drug effects metabolism MeSH
- Homer Scaffolding Proteins metabolism MeSH
- Cognition drug effects physiology MeSH
- Cerebral Cortex drug effects metabolism MeSH
- Neural Pathways drug effects metabolism MeSH
- Exploratory Behavior drug effects physiology MeSH
- Rats, Long-Evans MeSH
- Nerve Tissue Proteins metabolism MeSH
- Space Perception drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Analgesia methods psychology MeSH
- Dopamine secretion MeSH
- Mental Disorders drug therapy physiopathology psychology MeSH
- Individuality MeSH
- Humans MeSH
- Nociception drug effects MeSH
- Parkinson Disease drug therapy physiopathology psychology MeSH
- Exploratory Behavior physiology MeSH
- Placebo Effect * MeSH
- Psychophysiology methods MeSH
- Anticipation, Psychological physiology MeSH
- Check Tag
- Humans MeSH
In the present study, the effect of the medial septal (MS) lesions on exploratory activity in the open field and the spatial and object recognition memory has been investigated. This experiment compares three types of MS lesions: electrolytic lesions that destroy cells and fibers of passage, neurotoxic - ibotenic acid lesions that spare fibers of passage but predominantly affect the septal noncholinergic neurons, and immunotoxin - 192 IgG-saporin infusions that only eliminate cholinergic neurons. The main results are: the MS electrolytic lesioned rats were impaired in habituating to the environment in the repeated spatial environment, but rats with immuno- or neurotoxic lesions of the MS did not differ from control ones; the MS electrolytic and ibotenic acid lesioned rats showed an increase in their exploratory activity to the objects and were impaired in habituating to the objects in the repeated spatial environment; rats with immunolesions of the MS did not differ from control rats; electrolytic lesions of the MS disrupt spatial recognition memory; rats with immuno- or neurotoxic lesions of the MS were normal in detecting spatial novelty; all of the MS-lesioned and control rats clearly reacted to the object novelty by exploring the new object more than familiar ones. Results observed across lesion techniques indicate that: (i) the deficits after nonselective damage of MS are limited to a subset of cognitive processes dependent on the hippocampus, (ii) MS is substantial for spatial, but not for object recognition memory - the object recognition memory can be supported outside the septohippocampal system; (iii) the selective loss of septohippocampal cholinergic or noncholinergic projections does not disrupt the function of the hippocampus to a sufficient extent to impair spatial recognition memory; (iv) there is dissociation between the two major components (cholinergic and noncholinergic) of the septohippocampal pathway in exploratory behavior assessed in the open field - the memory exhibited by decrements in exploration of repeated object presentations is affected by either electrolytic or ibotenic lesions, but not saporin.
- MeSH
- Maze Learning drug effects physiology MeSH
- Hippocampus drug effects pathology physiology MeSH
- Immunotoxins toxicity MeSH
- Rats MeSH
- Neurotoxins toxicity MeSH
- Exploratory Behavior drug effects physiology MeSH
- Rats, Wistar MeSH
- Recognition, Psychology drug effects physiology MeSH
- Septal Nuclei drug effects pathology physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Potentiation of GABAergic inhibition is a mechanism of action of many antiepileptic drugs. The potential use of an agonist of GABAA receptors, muscimol, as an antiepileptic drug was studied in immature rats by assessing anticonvulsant activity and side effects on motor activities. Anticonvulsant action was tested in two models of seizures (pentetrazol-induced convulsions and cortical epileptic afterdischarges). Off target effect on motor performance was assessed in a battery of tests and in the open field in three age groups (12-, 18- and 25-day-old rats). Muscimol was administered in doses from 0.1 to 1mg/kg i.p. Only the 1 mg/kg dose exhibited marked anticonvulsant effect against pentetrazol-induced convulsions in 12- and 18-day-old rats, proconvulsant effect was observed in the second model in 18- and 25-day-old rats as prolongation of afterdischarges. Even the 0.5 mg/kg dose suppressed spontaneous locomotion and heavily compromised motor performance. The effect on motor activity was marked in the youngest group and decreased with age. Due to the low anticonvulsant potency and serious side effects, systemic administration of a competitive agonist of GABAA receptors in immature animals is not a promising strategy for new anticonvulsants.
- MeSH
- GABA-A Receptor Agonists pharmacology MeSH
- Anticonvulsants pharmacology MeSH
- Electroencephalography MeSH
- Epilepsy drug therapy physiopathology MeSH
- Disease Models, Animal MeSH
- Brain drug effects growth & development physiopathology MeSH
- Muscimol pharmacology MeSH
- Neuropsychological Tests MeSH
- Exploratory Behavior drug effects physiology MeSH
- Pentylenetetrazole MeSH
- Motor Activity drug effects physiology MeSH
- Rats, Wistar MeSH
- Severity of Illness Index MeSH
- Age Factors MeSH
- Dose-Response Relationship, Drug MeSH
- Seizures drug therapy physiopathology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
We have previously shown that chronic renal failure in rats induces changes in motor activity and behavior. Similar work on the possible effects of acute renal failure (ARF) induced by cisplatin (CP) is lacking. This is the subject matter of the current work. CP was injected intraperitoneally (i.p.) at a single dose of 20 mg/kg to induce a state of ARF, and three days later, its effects on motor activity, thermal and chemical nociceptive tests, neuromuscular coordination, pentobarbitone-sleeping time, exploration activity and two depression models were investigated. The platinum concentration in the kidneys and brains of mice was also measured. The occurrence of CP-induced ARF was ascertained by standard physiological, biochemical and histo-pathological methods. CP induced all the classical biochemical, physiological and histopathological signs of ARF. The average renal platinum concentration of CP-treated mice was 5.16 ppm, but there was no measurable concentration of platinum in the whole brains. CP treatment significantly decreased motor and exploration activities, and increased immobility time in depression models, suggesting a possible depression-like state. There was also a significant decrease in neuromuscular coordination in CP-treated mice. CP, given at a nephrotoxic dose, induced several adverse motor and behavioral alterations in mice. Further behavioral tests and molecular and biochemical investigations in the brains of mice with CP-induced ARF are warranted.
- MeSH
- Acute Kidney Injury chemically induced pathology MeSH
- Cisplatin toxicity MeSH
- Depression chemically induced psychology MeSH
- Mice MeSH
- Random Allocation MeSH
- Exploratory Behavior drug effects physiology MeSH
- Motor Activity drug effects physiology MeSH
- Antineoplastic Agents toxicity MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The aim of the present study was to investigate the impact of prenatal and postnatal methamphetamine (MA) exposure on behavior and anxiety in adult male and female rats. Mothers were daily exposed to injection of MA (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother raised 6 saline-exposed pups and 6 MA-exposed pups. Based on the prenatal and postnatal exposure 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in the Open field (OF) and in the Elevated plus maze (EPM) in adulthood. Locomotion, exploration, immobility and comforting behavior were evaluated in the OF, while anxiety was assessed in the EPM. While prenatal MA exposure did not affect behavior and anxiety in adulthood, postnatal MA exposure (i.e. MA administration to lactating mothers) induced long-term changes. Specifically, adult female rats in diestrus and adult males postnatally exposed to MA via breast milk (S/MA and MA/MA) had decreased locomotion and exploratory behavior in the OF and showed increased anxiety-like behavior in the EPM when compared to female rats in diestrus or males postnatally exposed to saline (S/S and MA/S). In adult females in proestrus, postnatal exposure to MA affected only exploratory behavior in the OF when compared to rats in proestrus postnatally exposed to saline. Thus, the present study shows that postnatal exposure to MA via breast milk impairs behavior in unfamiliar environment and anxiety-like behavior of adult male and female rats more than prenatal MA exposure.
- MeSH
- Analysis of Variance MeSH
- Video Recording MeSH
- Maze Learning drug effects MeSH
- Estrous Cycle drug effects MeSH
- Dopamine Uptake Inhibitors adverse effects MeSH
- Rats MeSH
- Maternal Behavior drug effects MeSH
- Methamphetamine adverse effects MeSH
- Disease Models, Animal MeSH
- Animals, Newborn MeSH
- Exploratory Behavior drug effects physiology MeSH
- Sex Characteristics MeSH
- Motor Activity drug effects physiology MeSH
- Pregnancy MeSH
- Immobility Response, Tonic drug effects MeSH
- Anxiety physiopathology MeSH
- Prenatal Exposure Delayed Effects physiopathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH