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PubMed2004

Exploratory behavior of F2 crosses of mouse lines selected for different brain weight: a multivariate analysis.

Principal component analysis of behavioural measures together with body and brain weight of hybrid F2 mice crosses between two lines selected for large (LB) and small (SB) brain weight yielded eight-factor solution explaining 75.1% of total variance. Two of eight factors had sufficient loading on brain weight and several behavioural measures. The factor analysis showed that, among F2 hybrids, mice with larger brain weight were characterised, in open-field test, by higher scores of locomotion in the periphery of arena and of rearing, as well as less frequent grooming and freezing than mice with smaller brain weight. F2 hybrids with larger brain weight moved faster and displayed stereotyped behaviour in the cross-maze test more frequently. In general, this diversity is in accord with the behaviour differences between parent LB and SB lines. The results show that, in mice fear-anxiety and stereotypic behaviours, which are known to interfere with normal exploration and learning of the environment, are causally connected with brain weight.

Animals↗

PubMed2000

Evidence that total extract of Hypericum perforatum affects exploratory behavior and exerts anxiolytic effects in rats.

Clinical trials have extensively reported the ability of Hypericum perforatum extracts to exert a significant antidepressant activity. Hypericin, the main constituent of H. perforatum extract, is no more regarded as the active principle of the antidepressant activity of the drug. Hence, the question of which constituents are involved in the basic activity of the total extract, is still waiting for an answer. In the present study we focused our attention on the potential anxiolytic activity of H. perforatum total extract, and of some pure components such as protohypericin and a fraction containing hypericin and pseudohypericin. Herein we report that the total extract of H. perforatum increases the locomotor activity in the open field and exerts anxiolytic activity in the light-dark test, whereas the single components did not show any effect. Interestingly, the anxiolytic activity of the total extract was blocked by pretreatment of rats with the benzodiazepine antagonist Flumazenil, hence suggesting an implication of benzodiazepine receptor activation in the anxiolytic effect of H. perforatum extract. Electrophysiological studies, performed to gain more information on the mechanism of action, showed that hypericin reduced the GABA-activated chloride currents, while pseudohypericin did an opposite effect. Furthermore, both hypericin and pseudohypericin inhibited the activation of NMDA receptors.

Animals↗

PubMed2004

Influence of hippocampectomy on habituation, exploratory behavior, and spatial memory in rats.

Two frequently cited functions of the hippocampus are mediation of spatial memories and habituation. The present investigation employed head-shake response (HSR) as the habituated behavior in intact and bilaterally hippocampectomized rats. This HSR appears to be minimally influenced by spatial cues. These rats were further tested on two behavioral paradigms that make use of spatial cues, namely open field object exploration, and the Morris water maze. The results indicate that hippocampectomized rats revealed habituation of the HSR, but not to objects within the open field. In agreement with previous reports, hippocampectomized rats were severely impaired both in acquiring and recalling the location of the submerged platform in the Morris water maze task. In a separate experiment independent groups of rats were trained on one of these three paradigms, and tissues were collected from hippocampal, prefrontal, and piriform cortices for the measurement of matrix metalloproteinases (MMPs) as markers of neural plasticity. There were significant MMP-9 elevations in the prefrontal and piriform cortices of rats tested using the object exploration task, in the prefrontal and hippocampal cortices of rats that solved the Morris water maze task, but minimal MMP changes in any tissues taken from HSR habituated rats. These results question the hypothesis that habituation is solely mediated by the hippocampus in favor of a process that utilizes different brain structures and degrees of neural plasticity dependent upon task requirements.

Animals↗

PubMedDate not supplied

[Effect of the local administration of 5,7-DHT and 6-OHDA into the neocortex on the learning and exploratory behavior of rats in an open field].

On Wistar rats characteristics were studied of investigating behaviour in the open field, of learning of conditioned food-reinforced reaction and also of BA and their metabolites content in various brain structures under local intracerebral injections of specific neurotoxins; 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (5,7-DHT), abolishing correspondingly catecholaminergic and serotoninergic terminals. Bilateral injection of 6-OHDA in the neocortex led to a weakening of rats investigating activity in the open field and to an increase of the time of fulfillment of the forming of conditioned food-reinforced reaction. Administration of 5,7-DHT was accompanied by an increase of the investigating behaviour in the open field and a reduction of the duration of the forming of conditioned reaction. Administration of 6-OHDA to the neocortex caused a lowering of catecholamines level in the frontal area of the neocortex and the hippocampus. Analogous administration of 5,7-DHT elicited simultaneously with a deep level lowering of 5-HT and its metabolite in these structures, a change of catecholamines content which testifies to a lesser specificity of the neurotoxin 5,7-DHT in comparison with 6-OHDA. Structures lesion of serotoninergic and catecholaminergic systems of the frontal cortex and the hippocampus brought about by a local administration of 6-OHDA and 5,7-DHT in the neocortex was accompanied by differently directed changes in animals behaviour.

5,7-Dihydroxytryptamine↗

PubMed1981

Effects of scopolamine, pilocarpine, and oxotremorine on the exploratory behavior of two psychogenetically selected lines of rats in a complex maze.

Rats of two psychogenetically selected lines received pretest IP injections of scopolamine hydrobromide (0.25, 1.0, or 4.0 mg/kg), pilocarpine hydrochloride (3.0, 6.0, or 12.0 mg/kg) or oxotremorine sesquifumarate (0.2, 0.4 or 0.8 mg/kg) and were subsequently placed in a complex enclosed maze of the Dashiell type that included a small, central, illuminated arena. Animals receiving pilocarpine or oxotremorine injections were pretreated with methscopolamine to counter the peripheral actions of these muscarinic cholinergic agonists. Following vehicle injections, Roman High-Avoidance rats (RHA/Verh) were significantly more active, explored more maze sectors, and required less time to activate the initial 24 different photocell units uniformly distributed throughout the maze than Roman Low-Avoidance rats (RLA/Verh). Scopolamine, pilocarpine, and oxotremorine depressed locomotor activity, reduced the explored area, and increased the time required to activate the initial 24 different photocell units within this complex maze for both RHA/Verh and RLA/Verh rats. Although the doses of scopolamine injected were approximately equally effective in both rat lines (except for total maze activity), the RHA/Verh rats exhibited significant alterations in several measures of maze patrolling after treatment with the lowest dose of pilocarpine, whereas the RLA/Verh rats did not. In contrast, most of the RLA/Verh rats exhibited very pronounced tremors following treatment with the highest dose of oxotremorine, but none of the RHA/Verh rats did. These results demonstrate that manipulation of the central cholinergic system with scopolamine, pilocarpine, or oxotremorine, despite their different pharmacological mechanisms, impair maze patrolling. Furthermore, the results suggest that the two psychogenetically bred lines of rats investigated are differentially sensitive to central cholinergic manipulation with the muscarinic receptor agonists pilocarpine and oxotremorine.

Animals↗

PubMed2005

Study of CA1 place cell activity and exploratory behavior following spatial and nonspatial changes in the environment.

Changes in the spatial arrangement or identity of objects inside a familiar environment induce reexploration. The present study looks at modifications of place cell activity during such renewed exploration. Hungry rats foraged for food in a cylinder with a salient cue card attached to the wall and with two distinct objects at fixed positions on the floor relative to each other and to the cue card. Once a set of CA1 place cells was recorded in this standard configuration, additional sessions were done after two kinds of manipulation. In the first, the two objects were rotated as a rigid set 90 degrees counterclockwise around the cylinder center while leaving the cue card in place; this was considered a spatial change. The effects of rotating the objects were different for fields near the objects (near fields) and fields far from the objects (far fields). Object rotation altered most near fields in complex ways, including remapping and cessation of firing. Near fields that remained intact after object rotation underwent unpredictable rotations that frequently departed considerably from the expected value of 90 degrees CCW. In contrast, the only change induced in far fields was a reduction of discharge rate on day 1, but not day 2, exposures of the rat to the rotated objects. The effects on both near and far fields were reversed when the objects were returned to their standard position. In the second manipulation, substitution of one of the two familiar objects with a novel object, a nonspatial change, had no detectable effect on place cell activity, regardless of field location. The sensitivity of hippocampal place cells to spatial changes but not to nonspatial changes is in agreement with earlier results showing that hippocampal lesions abolish reexploration after spatial but not after nonspatial object manipulations. The fact that reexploration is accompanied by place cell changes after spatial but not nonspatial changes reinforces the role that the hippocampus is believed to play in navigational computing and is perfectly compatible with the idea that another brain structure, likely perirhinal cortex, is responsible for object recognition.

Action Potentials↗

PubMedDate not supplied

The effects of neonatal administration of clonazepam on passive avoidance and on social, aggressive and exploratory behavior of adolescent male rats.

Male offspring of hooded Lister rats were fostered at birth to form experimental litters of eight. Within each litter pups were randomly allocated among drug groups. Administration of clonazepam (1-5 mg/kg/day) to pups from neonatal days 1-21 resulted in high mortality, at least partly due to impaired ultrasonic calling. Pups treated with 0.1, 0.5 or 1 mg/kg/day throughout the preweaning period were then tested undrugged during adolescence to assess any lasting behavioral changes. There were no significant changes in the social interaction test or in the acquisition or retention of a passive avoidance task. However, neonatal treatment with clonazepam (0.1 mg/kg) did produce significantly less exploratory head-dipping and locomotor activity in a holeboard. This dose also enhanced offensive behaviors when rats were resident in their home-cages and confronted with an intruder, but increased submissive behaviors when the treated rats were intruding into another rat's territory. Treatment with higher doses of clonazepam (0.5 and 1 mg/kg) produced more dominance behaviors when the pups were intruders. Since the main behavioral changes were found in the lowest dose group, which did not show any weight loss, they are unlikely to be secondary to changes in the risk of mortality.

Aggression↗

PubMed1981

The relationship of excessive exploratory behavior in wakefulness to paradoxical sleep without atonia.

The hypothesis that cats exhibiting paradoxical sleep (PS) without atonia are more active than normal in wakefulness was tested. To provide a quantitative measure of locomotor activity, 15 cats were subjected to an open-field test of activity for 5 one-hour or 10 half-hour sessions before and after placement of bilateral pontine tegmental lesions, which induce PS without atonia. Thirteen of the cats had PS without atonia and showed significant (p less than 0.05) increases in open-field activity, which was judged to be exploratory in nature, rather than aimless pacing. Increases ranged from 30-261%. In spite of the abnormal increase in antigravity muscle tone during PS postoperatively, hypertonia was not present during wakefulness. Of the 2 cats without elaborate behavior during PS, 1 had a significant decrease in activity. Its lesion may have damaged a lateral brainstem locomotor region. The same effect was obtained with unilateral damage of this region in 1 of 2 cats subjected to 2-stage operations. The results were used to develop the argument that peripheral motor inhibition during PS depends on suppression of a brainstem locomotor region in addition to direct inhibition of spinal motor neurons.

Animals↗

PubMed1997

Removal of the submaxillary salivary glands and infection with the trematode Schistosoma mansoni alters exploratory behavior and pain thresholds in female mice.

In this study, CD-1 female mice, deprived of the submaxillary salivary glands, were infected with S. mansoni and their behavior was observed 15 weeks after infection, when the eggs of the parasite are present in the brain. Sialectomized infected mice showed changes in exploratory activity, sniffing, and wall-rearing in the open-field and in the black/white box, but no differences in pain sensitivity were observed on the hot plate. The present results suggest that the modifications in the behavior of sialectomized infected mice might be associated with the inability of the animals to cope with the aversive effects of the infection and, most probably, with modifications in the levels of polypeptides released into the bloodstream by the salivary glands, affecting the NGF-responsive cells of the nervous, endocrine, and immune systems.

Animals↗

PubMed1984

A genetically controlled hippocampal transmitter system regulating exploratory behavior in mice.

Male C57BL/6 and DBA/2 mice were intrahippocampally microinjected with muscimol (0.5 microgram), given 15 min prior to individual 20-min exploration tests in a novel environment, and compared to saline controls. The GABA agonist reduced various exploratory acts and locomotor activity in strain C57BL/6 and increased the scores in DBA/2. In conjunction with similar opposite effects previously found with intra-hippocampal methylscopolamine and naloxone, these findings suggest that the opioid modulation of the hippocampal cholinergic mechanism which facilitates behavioral responses to novelty in mice is effectuated indirectly through an inhibitory GABAergic system. The functioning of these regulatory systems appears to depend on genotype.

Animals↗

PubMed1976

Effect of postnatal dietary protein and energy restriction on exploratory behavior in young pigs.

Three-week-old pigs were subjected to dietary energy or protein restriction so as to prevent weight gain over a period of 8 weeks. During the last week of restriction their responses to a novel object introduced into an exploratory test situation were measured. The malnourished pigs exhibited indifference to the object, taking longer to make contact with it, spending less time playing with it, but not showing evidence of fear or avoidance of the object or the area in which it was located. Following 6 weeks of nutritional rehabilitation, the previously malnourished pigs again displayed less approach behavior to the novel object than controls, but the effect was substantially reduced. These observations are interpreted to support our hypothesis that a major mechanism through which early malnutrition produces long-term effects on behavior is by disturbing those behaviors required for gathering information from the environment.

Animals↗

PubMed2006

The exploratory behavior of rats in an open environment optimizes security.

When given a locomotor/exploratory test in the laboratory, rats form one or more home bases, operationally defined as places where they spend a disproportionate period of their time and from which they make excursions. Because exploratory tests in the laboratory necessarily restrict the animals' movements, the cause of exploration (e.g., fear, curiosity, innate disposition) and the extent to which organization is imposed by the restriction of the testing environment has not been fully examined. In the present study, rats received exploratory tests in environments in which restrictions were remote; in a parking lot or on a playing field. Each rat began a test in one of three conditions: in a small refuge, within a transparent open home cage, or beside a landmark. In the parking lot, the rats failed to leave the small refuge, made excursions from the home cage, and left the landmark, usually at a gallop, and made no movements of returning. On the playing field they remained in the small refuge, left and returned to the open home cage, and were more likely to permanently leave the landmark at a gallop. Rats that displayed a strong preference for the landmark over three test sessions in a laboratory, also immediately left the same landmark when tested on the playing field. The pattern of behavior, in which the rats failed to explore from a secure starting position and were increasingly likely to run away as security decreased, suggests that a primary function of locomotor behavior in a novel environment is to optimize security. The results are discussed in relation to the advantages of investigating the influence of neural processes on exploration in terms optimization theory versus motivational theory.

Animals↗

PubMed2006

Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior.

Coffin-Lowry Syndrome (CLS) is an X-linked syndromic form of mental retardation associated with skeletal abnormalities. It is caused by mutations of the Rsk2 gene, which encodes a growth factor regulated kinase. Gene deletion studies in mice have shown an essential role for the Rsk2 gene in osteoblast differentiation and function, establishing a causal link between Rsk2 deficiency and skeletal abnormalities of CLS. Although analyses in mice have revealed prominent expression of Rsk2 in brain structures that are essential for learning and memory, evidence at the behavioral level for an involvement of Rsk2 in cognitive function is still lacking. Here, we have examined Rsk2-deficient mice in two extensive batteries of behavioral tests, which were conducted independently in two laboratories in Zurich (Switzerland) and Orsay (France). Despite the known reduction of bone mass, all parameters of motor function were normal, confirming the suitability of Rsk2-deficient mice for behavioral testing. Rsk2-deficient mice showed a mild impairment of spatial working memory, delayed acquisition of a spatial reference memory task and long-term spatial memory deficits. In contrast, associative and recognition memory, as well as the habituation of exploratory activity were normal. Our studies also revealed mild signs of disinhibition in exploratory activity, as well as a difficulty to adapt to new test environments, which likely contributed to the learning impairments displayed by Rsk2-deficient mice. The observed behavioral changes are in line with observations made in other mouse models of human mental retardation and support a role of Rsk2 in cognitive functions.

Abnormalities, Multiple↗

PubMed1986

Histamine in dorsal and ventral hippocampus. II. Effects of H1 and H2 histamine antagonists on exploratory behavior in male rats.

The effects on Hole-Board behavior of histamine (HA) microinjected into different parts of the hippocampus and the effects of pyrilamine (PYR, an H1-histamine antagonist), ranitidine (RAN, an H2-histamine antagonist) or alpha-fluoromethyl-histidine (alpha-FMH, an irreversible inhibitor of the HA synthetizing enzyme) injected into the hippocampus on behavior were studied. Forty five nMol of HA were injected stereotaxically into the dorsal or ventral hippocampus. Five min later, Hole-board behavior was measured. It was observed that HA inhibited locomotion and rearing only in the rats injected into the ventral hippocampus. In other experiments, animals were microinjected into the ventral hippocampus with 135 nMol of PYR or RAN in 1 microliter of saline solution. Ten min later, they were microinjected with 45 nMol of HA. Hole-board exploratory activity was measured 5 min thereafter. Results showed that both PYR and RAN were effective in counteracting the inhibitory effect of HA on locomotor activity, but only RAN was able to block the inhibitory action of HA on rearing behavior. Head-dipping frequency was not affected by these treatments. In rats microinjected with 20 nMol of alpha-FMH, increased scores of locomotion were observed but the other behaviors (head-dipping frequency, grooming and rearing) were not affected. The present results support the hypothesis that HA in hippocampus may be exerting a regulatory role on behavior by interaction with H1 and H2 receptors.

Aminopyridines↗

PubMed2000

Effects of subchronic methylphenidate hydrochloride administration on the locomotor and exploratory behavior of prepubertal mice.

The increasing use of methylphenidate hydrochloride (MPH) in children led us to examine the effects of MPH administration in developing mice. Male CD-1 mice were administered MPH (40 mg/kg, subcutaneously) or saline daily from postnatal days 26-32. The mice were then tested from postnatal days 33-37 for locomotion and exploration in the open field, anxiety in the elevated plus maze, and learning in the Morris water maze. The results indicate that MPH-pretreated mice were more exploratory and less fearful in the open field, entering more center squares than saline controls. MPH-pretreated mice also exhibited less anxiety, spending more time in the open arm and exhibiting more head dips in the elevated plus maze than controls. There was no significant difference between MPH and saline-treated mice in the time taken to find the visible or hidden platform in the water maze task. The results indicate that treatment with MPH has significant effects on later behavior, reducing fear and anxiety, and increasing exploration, but no effect on performance in a spatial learning task.

Animals↗

PubMed2005

Effects of a 5-HT7 receptor antagonist DR4004 on the exploratory behavior in a novel environment and on brain monoamine dynamics in mice.

The present study examined whether serotonin (5-hydroxytryptamine; 5-HT)7 receptors play a role in the modulation of emotionality in mice using the selective 5-HT7 receptor antagonist 2a-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl]-2a,3,4,5-tetrahydrobenzo (c,d)indol-2-(1H)-one (DR4004). The emotionality of mice was evaluated in terms of exploratory activity in the hole-board test. The mice treated with DR4004 (2.5-10 mg/kg, i.p.) displayed a dose-dependent decrease in locomotor activity by moving less distance in the hole-board, and statistically significant decreases were observed at 5 and 10 mg/kg. On the other hand, DR4004 (10 mg/kg, i.p.) did not affect spontaneous motor activity. In a neurochemical study, decreases in amygdaloid dopamine and 5-HT turnover were observed in mice in which locomotor activity in the hole-board test was attenuated following the administration of DR4004 (10 mg/kg, i.p.). Also, a simple linear regression analysis revealed that locomotor activity on the hole-board was significantly correlated with dopamine and 5-HT turnover in amygdala. Furthermore, co-injection of the selective dopamine reuptake inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR12909; 1.25-5 mg/kg, i.p.) or the selective 5-HT reuptake inhibitor fluvoxamine (20 mg/kg, i.p.) significantly reversed the DR4004 (10 mg/kg, i.p.)-induced decrease in locomotor activity in the hole-board test. These findings constitute the behavioral evidence that 5-HT7 receptors may play a role in the modulation of emotionality. Furthermore, it is also suggested that amygdaloid dopamine and 5-HT neuronal systems may be involved in this modulation.

Amygdala↗

PubMed1983

Acute and chronic amphetamine treatment: differential modification of exploratory behavior in a radial maze.

Mice permitted to explore an 8-arm radial maze displayed high levels of spontaneous alternation as measured by the frequency of visiting (a) the 4 least recently entered arms, (b) the 2 least recently visited arms, and (c) sequences of arms which are adjacent to one another. Acute treatment with low doses of amphetamine (1.0 mg/kg) eliminated the alternation tendency. Higher doses (5.0-7.0 mg/kg) also produced marked stimulus perseverance, such that mice tended to revisit the two arms that had been most recently entered. With repeated amphetamine treatment the perseverance tendency was attenuated. The abatement of perseverance in the radial maze did not appear to reflect simply the reduction in the potency of the drug. That is, the reduction of perseverance after chronic exposure to amphetamine was not accompanied by recovery of normal exploratory patterns. In fact, the alternation and adjacent alternation patterns typical of naive animals were absent in mice chronically treated with amphetamine even when tested in the nondrug state. It was suggested that the attenuation of amphetamine induced perseverance after chronic amphetamine administration may reflect a breakdown of normal behavior patterns rather than the development of a genuine tolerance.

Animals↗

PubMed1986

Rehabilitation from neonatal hypothyroidism: spontaneous motor activity, exploratory behavior, avoidance learning and responses of pituitary--thyroid axis to stress in male rats.

Long-Evans male rats were made hypothyroid from birth by the addition of 6-N-propylthiouracil (PTU) to their drinking water (0.1%). A group of animals was rehabilitated beginning at postnatal day 25 by withdrawal of the PTU from the drinking water. Subsequently, the rats were tested for a variety of behavioral tasks. Serum concentrations of thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) were determined by radioimmunoassay. At 50 days of age, PTU-treated rats had non-detectable levels of T4 but an eight-fold increase of TSH. In 50-day-old, neonatally hypothyroid but rehabilitated rats, serum TSH and T3 were normal, although T4 was still significantly lower. At 90 days of age, basal levels of TSH and thyroid hormones were normal in the rehabilitated rats, but thyroid hormone secretion in response to various types of neural stress was markedly altered. Comparison of passive avoidance learning revealed no significant alteration in the memory retention of either PTU-treated or rehabilitated animals. The 50-day-old, rehabilitated rats showed increased locomotor activity both in running-wheel and in hole-board tests; this hyperactivity, though markedly reduced, still persisted at day 90. In the early phase of rehabilitation (50 days of age), decreases in exploratory activity and lack of habituation occurred with the hole-board test; by the late phase of rehabilitation (90 days of age) these behavioral parameters had become normal. These results suggest generally longer periods of plasticity of the brain and better prospects for rehabilitation from neonatal cretinoid retardation than commonly believed. Specifically, the pituitary-thyroid system and neural mechanisms integrating adaptive behavior possess considerable capacity for spontaneous recovery from hypothyroidism; certain types of altered neuroendocrine and behavioral responses appear to be less amenable to rehabilitation or require longer periods for complete rehabilitation.

Animals↗