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Exploration in outbred mice covaries with general learning abilities irrespective of stress reactivity, emotionality, and physical attributes.

Across multiple learning tasks (that place different sensory, motor, and information processing demands on the animals), we have found that the performance of mice is commonly regulated by a single factor ("general learning") that accounts for 30-40% of the variance across individuals and tasks. Furthermore, individuals' general learning abilities were highly correlated with their propensity to engage in exploration in an open field, a behavior that is potentially stress-inducing. This relationship between exploration in the open field and general learning abilities suggests the possibility that variations in stress sensitivity/responsivity or related emotional responses might directly influence individuals' general learning abilities. Here, the relationship of sensory/motor skills and stress sensitivity/emotionality to animals' general learning abilities were assessed. Outbred (CD-1) mice were tested in a battery of six learning tasks as well as 21 tests of exploratory behavior, sensory/motor function and fitness, emotionality, and stress reactivity. The performances of individual mice were correlated across six learning tasks, and the performance measures of all learning tasks loaded heavily on a single factor (principal component analysis), accounting for 32% of the variability between animals and tasks. Open field exploration and seven additional exploratory behaviors (including those exhibited in an elevated plus maze) also loaded heavily on this same factor, although general activity, sensory/motor responses, physical characteristics, and direct measures of fear did not. In a separate experiment, serum corticosterone levels of mice were elevated in response to a mild environmental stressor (confinement on an elevated platform). Stress-induced corticosterone levels were correlated with behavioral fear responses, but were unsystematically related to individuals' propensity for exploration. In total, these results suggest that although general learning abilities are strongly related to individuals' propensity for exploration, this relationship is not attributable to variations in sensory/motor function or the individuals' physiological or behavioral sensitivity to conditions that promote stress or fear.

Animals↗

A monoamine oxidase inhibitor reverses the 'separation syndrome' in a new hamster separation model of depression.

A broad spectrum monoamine oxidase inhibitor, tranylcypromine sulfate (Parnate) was tested in a new hamster separation model of depression. In this paradigm, male dwarf hamsters show increases in body weight, decreases in exploratory behaviors, and decreases in social interactions, when separated from female mates. Tranylcypromine (10 mg/kg s.c. daily for 14 days) effectively reduced body weight, increased exploration, and increased social interaction, in the separated males. Subsequent treatment with saline restored the separation-induced changes in body weight, exploratory behaviors, and other social behaviors. The 'separation syndrome' in dwarf hamsters appears to be completely reversed by at least one antidepressant treatment.

Animals↗

Changes in spontaneous behavior in the dog following oral administration of L-deprenyl.

An open-field activity test was developed for studying the effect of a single oral dose (range of 0.1-5 mg/kg) of L-deprenyl on spontaneous behavior in the dog. A computer program was used to quantify observations of locomotor activity, directed sniffing, urination, grooming, inactivity, jumping, rearing, and vocalization during a 10-min baseline and posttreatment session. Three dose-dependent behavioral changes were observed: an overall decrease in directed sniffing, an increase in total locomotor activity in females, and a decrease in frequency of urination in males. These effects were only seen at the dose levels of 2 mg/kg or higher. Computer-assisted tracings of behavioral patterns showed increased stereotypical behavior and decreased exploratory behavior at the high-dose levels. These behavioral effects are most likely due to either increased levels of phenylethylamine resulting from inhibition of monoamine oxidase B and/or the production of amphetamines as a result of the metabolism of L-deprenyl.

Aging↗

Psychosocial stress alters ethanol's effect on open field behaviors.

Psychosocial stress, including social rank status, has been shown to alter spontaneously occurring behaviors in rodents as well as the behavioral effects of drugs of abuse. In this study, rats were repeatedly evaluated in a modified open field following: their initial exposure, and after intraperitoneal injections of saline and 0.75 g/kg ethanol (EtOH). All subjects were first tested while under single housing conditions, then again following 35 days of differential housing (singly or 3 rats/cage) with social status determined by scoring agonistic behavior at triad formation. The data suggest that (1) future subordinate rats differed with respect to specific aspects of behavior displayed in a 'novel' open field arena, (2) future subordinate rats were more emotional since they showed greater "anxiety-like" behavior and less exploratory behavior, (3) subordinate rats were more impaired by the saline injection stress, (4) subordinate rats were more sensitive to the depressant effects of EtOH, (5) grooming behavior did not show habituation, in contrast to the other behaviors, but showed sensitization on the second test. Overall, subordinate rats may have differed from their cage mates in innate anxiety, and this may underlie their distinct response to both stressors and EtOH. Furthermore, while EtOH had mostly stimulant effects in naive rats, psychosocial stress and/or repeated testing resulted in enhancement of EtOH's depressant effects.

Animals↗

Severe reduction of rat defensive behavior to a predator by discrete hypothalamic chemical lesions.

Nonspecific lesion and stimulation methods have suggested that the hypothalamus is critical for the expression of defensive behavior, although the organization of neural circuits mediating such behavior is unclear. In the rat hypothalamus, we found that increased Fos levels were restricted to specific cell groups following presentation of a stimulus (predator) known to elicit partly innate defensive responses. The dorsal premammillary nucleus showed the most striking increase in Fos levels, and cell body-specific chemical lesions therein virtually eliminated two major components of defensive behavior but increased exploratory behavior, suggesting that this caudal hypothalamic nucleus plays a critical role in the expression of behavioral responses sometimes critical for survival of the individual. We have previously shown that the Fos-responsive cell groups in the medial hypothalamus are interconnected in a neural system distinct from those mediating reproductive and ingestive behaviors.

Animals↗

Neuropharmacological activity of Solanum nigrum fruit.

The ethanol extract of the fruit of Solanum nigrum L. (Solanaceae) was studied for its neuropharmacological properties on experimental animals. On intraperitoneal injection, the extract significantly prolonged pentobarbital-induced sleeping time, produced alteration in the general behavior pattern, reduced exploratory behavior pattern, suppressed the aggressive behavior, affected locomotor activity and reduced spontaneous motility. The observations suggest that the fruit of S. nigrum possesses potential CNS-depressant action.

Animals↗

In the search for a novel class of antipsychotic drugs: preclinical pharmacology of FG5803, a 1-piperazinecarboxamide derivative.

Comparative studies of the 1-piperazinecarboxamide derivative 4-[3-(4-fluorobenzoyl)propyl]-N-cyclohexyl-1-piperazinecarboxamide hydrochloride (FG5803) were made with clozapine and haloperidol. Receptor studies revealed that FG5803 potently and selectively bound to the serotonin type 2A receptors (Ki = 13 nM). FG5803 inhibited 5-hydroxytrophan- and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced head twitches, which indicated potent in vivo serotonin type 2A receptor antagonism. FG5803 caused an acute activation of the tuberoinfundibular dopamine neurons and produced only a transient rise in plasma prolactin. In behavioral studies in rats, FG5803 showed strong antagonistic action on presynaptic dopaminergic autoreceptors but only weak postsynaptic dopamine D2 blockade. FG5803 was not cataleptogenic and did not antagonize amphetamine-induced stereotypies. FG5803 was active in the reduction of aggressive behavior and spontaneous exploratory behavior in mice and rats. Therefore, FG5803 is expected to constitute a promising approach in the search for a novel class of antipsychotic drugs that have a broader spectrum of activity and fewer adverse effects than the conventional, antidopaminergic antipsychotics.

Animals↗

The effects of hippocampal damage on adaptation to novelty in rats.

Nurses are the primary care givers of disoriented individuals. More knowledge of how wayfinding is accomplished could help improve care and determine nursing therapies. Humans and animals wayfind most efficiently by forming mental images called cognitive maps. It is theorized that the hippocampus (HPC) is necessary for generating and updating cognitive maps. Further, it is known that HPC damage alters wayfinding ability. This study is a secondary analysis of Therrien's data to investigate effects of HPC lesion side and animal gender on exploratory behavior when novelty is introduced into a familiar environment. After rats with HPC or sham lesions were trained on a place navigation task that involved learning to use a fixed set of distal cues to locate a platform submerged under water, novelty was introduced on two test days. Exploratory behaviors measured were swim distances in all areas of the tank, orientation directly beneath the distal cues, and directional turn following placement in the water.

Adaptation, Psychological↗

Succinate causes oxidative damage through N-methyl-D-aspartate-mediated mechanisms.

In this study we investigated whether succinate, the accumulating substrate in succinate dehydrogenase (SDH) deficiencies and SDH inhibitor intoxication, causes lipoperoxidation and protein carbonylation, and if NMDA receptors are involved in the succinate-induced oxidative damage. Adult male mice (30-40 g) received an intracerebroventricular injection of succinic acid (0.7, 1.0 and 1.7 micromol/5 microl) or 0.9% NaCl (5 microl) and had their exploratory behavior assessed in an open field for 10 min. Succinate (0.7 and 1.0 micromol/5 microl) decreased locomotor activity behavior and increased thiobarbituric acid reactive substances (TBARS) and protein carbonylation in the forebrain. Conversely, 1.7 micromol of succinate did not alter locomotor activity or oxidative damage parameters. The involvement of NMDA receptors in the succinate-induced increase of total protein carbonylation content and exploratory behavior inhibition was assessed by co-administrating MK-801 (7 nmol/2.5 microl icv), a noncompetitive NMDA receptor antagonist, with succinate (1 micromol/2.5 microl icv). The co-administration of MK-801 protected against succinate-induced increase of total protein carbonylation and decrease of locomotor activity. These results suggest the involvement of NMDA receptors in these effects of succinate, which may of particular relevance for succinate-accumulating conditions, such as SDH inhibitors intoxication and inherited SDH deficiencies.

Animals↗

Estrogens influence behavioral responses in a kainic acid model of neurotoxicity.

The behavioral and neuroprotective effects of 17beta-estradiol (E2), on ovariectomized rats treated with a subconvulsive dose (7 mg/kg bw, ip) of kainic acid (KA), were examined. Estradiol was administered either acutely (150 mug/rat, ip) along with KA, 14 days post-ovariectomy, or chronically (sc capsules providing proestrus estrogen levels in serum) starting at ovariectomy. Exploratory behavior, as deduced by sniffing in the open field test, was reduced in KA-treated rats. Both hormonal schemes partially restored sniffing behavior in KA-lesioned subjects. Moreover, acute and chronic E2 administration in KA-treated rats resulted in increased vertical and horizontal activity of these animals in the open field test. Memory for object recognition was reduced following KA and was not restored by hormonal treatments. Acute, but not chronic, E2 coadministration with KA significantly impaired spatial performance in the water maze task, while KA alone had no effect. Both acute and chronic estradiol administration rescued hilar and CA1 neurons from KA-induced cell death. Chronic, but not acute, E2 increased neurofilament immunoreactivity in the mossy fibers of the dentate gyrus neurons, similarly to KA. Our results show that although estradiol administration in KA-treated rats has beneficial effects on cell survival, it has diverse effects on exploratory behavior, object, and spatial memory. Estradiol effects on KA-lesioned animals depended on the duration and timing of exposure to the hormone, implying different mechanisms of hormone actions.

Analysis of Variance↗

Dopamine D4 receptor gene and attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder is a prevalent disorder characterized by hyperactivity, impulsivity, and attentional dysfunction. It is familial and heritable. Its pathophysiology is thought to involve an abnormality of the brain's dopaminergic neurotransmitter system. Recent work has identified a distinct polymorphism of the dopamine D4 receptor gene in normal people with a behavioral temperament profile characterized by features of "novelty seeking" which include impulsive and exploratory behaviors. These personality traits are also characteristic of children with attention deficit hyperactivity disorder, especially the hyperactive-impulsive type. This study investigated the relationship between dopamine D4 receptor gene polymorphism, temperament categories, and attention deficit hyperactivity disorder in 81 children with the disorder and 24 control subjects. There was no significant association between dopamine D4 receptor gene alleles, Novelty Seeking traits, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of attention deficit hyperactivity disorder--Hyperactive impulsive type or Inattentive type.

Adolescent↗

The psychostimulant and rewarding effects of cocaine in histidine decarboxylase knockout mice do not support the hypothesis of an inhibitory function of histamine on reward.

RATIONALE AND OBJECTIVES: Lesion studies have shown that the tuberomammillary nucleus (TM) exerts inhibitory effects on the brain reward system. To determine whether histamine from the TM is involved in that reward inhibitory function, we assessed the stimulant and rewarding effects of cocaine in knockout mice lacking histidine decarboxylase (HDC KO mice), the histamine-synthesizing enzyme. If histamine actually plays an inhibitory role in reward, then it would be expected that mice lacking histamine would be more sensitive to the behavioral effects of cocaine. MATERIALS AND METHODS: The first experiment characterized spontaneous locomotion and cocaine-induced hyperactivity (0, 8, and 16 mg/kg, i.p.) in wild-type and HDC KO mice. The rewarding effects of cocaine were investigated in a second experiment with the place-conditioning technique. RESULTS: The first experiment demonstrated that histidine decarboxylase mice showed reduced exploratory behaviors but normal habituation to the test chambers. After habituation to the test chambers, HDC KO mice were slightly, but significantly, less stimulated by cocaine than control mice. This finding was replicated in the second experiment, when cocaine-induced activity was monitored with the place-conditioning apparatus. Furthermore, a significant place preference was present in both genotypes for 8 and 16 mg/kg cocaine, but not for 2 and 4 mg/kg. CONCLUSIONS: Our data confirm previous results demonstrating that HDC KO mice show reduced exploratory behaviors. However, contrary to the hypothesis that histamine plays an inhibitory role in reward, histamine-deficient mice were not more responsive to the psychostimulant effects of cocaine.

Animals↗

Activation of adenosine A(1) receptors alters behavioral and biochemical parameters in hyperthyroid rats.

Adenosine acting on A(1) receptors has been related with neuroprotective and neuromodulatory actions, protection against oxidative stress and decrease of anxiety and nociceptive signaling. Previous studies demonstrated an inhibition of the enzymes that hydrolyze ATP to adenosine in the rat central nervous system after hyperthyroidism induction. Manifestations of hyperthyroidism include increased anxiety, nervousness, high O(2) consumption and physical hyperactivity. Here, we investigated the effects of administration of a specific agonist of adenosine A(1) receptor (N(6)-cyclopentyladenosine; CPA) on nociception, anxiety, exploratory response, locomotion and brain oxidative stress of hyperthyroid rats. Hyperthyroidism was induced by daily intraperitoneal injections of l-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus and exploratory behavior, locomotion and anxiety were analyzed by open-field and plus-maze tests. We verified the total antioxidant reactivity (TAR), lipid peroxide levels by the thiobarbituric acid reactive species (TBARS) reaction and the free radicals content by the DCF test. Our results demonstrated that CPA reverted the hyperalgesia induced by hyperthyroidism and decreased the exploratory behavior, locomotion and anxiety in hyperthyroid rats. Furthermore, CPA decreased lipid peroxidation in hippocampus and cerebral cortex of control rats and in cerebral cortex of hyperthyroid rats. CPA also increased the total antioxidant reactivity in hippocampus and cerebral cortex of control and hyperthyroid rats, but the production of free radicals verified by the DCF test was changed only in cerebral cortex. These results suggest that some of the hyperthyroidism effects are subjected to regulation by adenosine A(1) receptor, demonstrating the involvement of the adenosinergic system in this pathology.

Adenosine↗

Critical evaluation of the Obscure Figures Test as an instrument for measuring "cognitive innovation".

The Obscure Figure Test has been conceptualized by Acker and McReynolds (1965) as a measure of Cognitive Innovation. As a general concept Cognitive Innovation refers to an integration of different kinds of behavioral systems, e.g., creativity and exploratory behavior. Considering recent research about the relationship between curiosity and creativity as well as basic assumptions underlying this test, it is hypothesized that this is an instrument for measuring creativity rather than curiosity. 41 boys and 41 girls ranging from 7 to 10 yr. of age were given a battery of tests of curiosity and creativity. There were significant correlations between Obscure Figures Test and creativity measures. No such relationships were found between obscure figures and curiosity measures. A factor analysis yielded two factors which could be interpreted as "visual exploration" and "creativity", the obscure figures being a marker variable on the latter factor. Results are discussed in terms of the theoretical assumptions underlying the concepts of curiosity, creativity, and Cognitive Innovation. Further implications with respect to the requirements for an operationalization of Cognitive Innovations are mentioned.

Child↗

[The open-field, non-stressed behavior of rats under the acute and chronic effect of imipramine and tranylcypromine, depending on the individual reaction type (emotional and non-emotional)].

The acute and prolonged effects of imipramine and tranylcypromine were studied on 30 emotive and 30 non-emotive mature male Wistar rats to determine whether the drugs affect the behavior of these two reaction types differently. We found that both drugs change the typical behavior of the rats in the open field, each in a different way. Acute doses of imipramine inhibit symptoms of anxiety as well as the exploratory behavior so that the rats appear totally disinterested in their environment. This finding seems to confirm the assumed central nervous suppressing effects of this drug as mentioned in the literature. Single doses of tranylcypromine have effects similar to those mentioned for imipramine; however, long-term use results in a "vitalisation" of behavior: symptoms of anxiety remain inhibited and exploratory behavior becomes dominant. Both drugs produced a certain "flattening" of behavior. Due to the effects of drugs used, the original behavioral differences without stress disappear. Prolonged use of tranylcypromine makes emotive rats totally non-emotive.

Animals↗

Indole-pyruvic acid, a tryptophan ketoanalogue, antagonizes the endocrine but not the behavioral effects of repeated stress in a model of depression.

Increased glucocorticoid secretion is frequent in mood disorders and is normalized by long-term antidepressant therapy. Many antidepressants act by increasing central serotonin transmission. We investigated the effects of a serotonin precursor, indole-pyruvic acid (IPA), in an animal model of depression based on repeated exposure to unpredictable stress. Rats were divided in groups, and IPA (20 mg/kg), the tricyclic antidepressant imipramine (IMI) (5 mg/kg), or vehicle was administered daily during 3 weeks of repeated exposure to various stressors according to the procedure described by Katz et al [Katz RJ, Roth KA, Carroll BJ (1981): Neurosci Biobehav Rev 5:247-251]. After treatment, rats were evaluated for stress-induced exploratory behavior and killed 24 hr later. Serum corticosterone levels and glucocorticoid receptor (GR) immunoreactivity (IR) in the nuclei of neurons located in the hippocampal subregion CA1 were also measured. Rats exposed to repeated stress showed a lower exploratory behavior score (p < 0.01), higher basal corticosterone levels (p < 0.01), and stronger GR IR in the hippocampus (p < 0.05) than control rats. All of these effects were antagonized by IMI treatment. IPA administration did not affect the behavioral response induced by repeated stress (p < 0.01) but normalized serum corticosterone levels. In addition, IPA treatment produced a decrease in GR IR (p < 0.05 versus control group) that was not modified by exposure to repeated stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Alterations of behavior and spatial learning after unilateral entorhinal ablation of rats.

The entorhinal cortex (EC) is the key input and output structure of the hippocampus. It plays a crucial role in sensory processing, memory and learning, as well as in mechanisms of epileptic seizures. Our previous studies on the 4-aminopyridin induced epilepsy model of rats showed that ablation of unilateral EC prompted weakening of limbic seizure manifestation, thus the possibility of therapeutical benefit of this kind of surgery can be risen. Open field, elevated plus-maze and Morris water-maze test were performed to analyze changes of the basal activity level, exploratory behavior, and spatial memory capacity, respectively, of adult Wistar rats having undergone left EC excision. Compared with the sham-operated control group, rats with lesions of the EC showed enhanced locomotor activity in the open-field test. The elevated plus-maze test revealed higher frequency of entries and more time spent in the open arms. Morris water-maze test suggested impairment of the spatial learning capacity following left lateral EC lesion. Therefore, our data showed that EC lesions induced hyperactivity, increased exploratory behavior, and impaired spatial learning. Entorhinal cortex ablation, as a potential method for controlling epileptic seizures has multiple effects on animals' behavior and spatial learning. To determine the cost-benefit ratio of a potential surgical intervention needs further experimental and human investigations.

Animals↗

Acute exposure to methylmercury at two developmental windows: focus on neurobehavioral and neurochemical effects in rat offspring.

The neurobehavioral and neurochemical effects produced by prenatal methylmercury exposure (8 mg/kg, gestational-days 8 or 15), were investigated in rats. On postnatal day 40, animals exposed to methylmercury and tested in the open field arena, showed a reduction in the number of rearings, whereas the number of crossings and resting time was not altered with respect to the age-matched control rats. The methylmercury-exposed groups showed a lower level of exploratory behavior as well as an impairment in habituation and working memory when subjected to the novel object exploration task. The neophobia displayed by methylmercury-exposed rats is unlikely to be attributed to a higher degree of anxiety. Prenatal methylmercury exposure did not affect motor coordination or motor learning in 40-day-old rats subjected to the balance task on a rotating rod, and it did not impair the onset of reflexive behavior in pups screened for righting reflex, cliff aversion and negative geotaxis. In cortical cell cultures from pups exposed to methylmercury during gestation, basal extracellular glutamate levels were higher, whereas the KCl-evoked extracellular glutamate levels were lower than that measured in cultures from rats born to control mothers. In addition, a higher responsiveness of glutamate release to N-methyl-D-aspartic acid receptor activation was evident in cortical cell cultures from pups born from methylmercury-treated dams than in cultures obtained from control rats. The present results suggest that acute maternal methylmercury exposure induces, in rat offspring, subtle changes in short-term memory as well as in exploratory behavior. These impairments seem to be associated to alterations of cortical glutamatergic signaling.

Analysis of Variance↗