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Influence of acute and repeated interleukin-2 administration on spatial learning, locomotor activity, exploratory behaviors, and anxiety.

Interleukin-2 (IL-2), released from activated T cells, influences central neurochemical functioning, and IL-2 immunotherapy in cancer patients may provoke neuropsychiatric and cognitive disturbances. In this study, acute, systemic IL-2 did not influence Morris water-maze performance in mice. In contrast, chronic IL-2 impaired performance when the position of the escape platform varied over days but was without effect when the platform position was fixed. These effects could not be attributed to illness, because IL-1beta, which induces marked malaise, did not influence water-maze performance. Chronic IL-2 produced modest reductions in exploration and approach to a novel stimulus, effects not seen after acute treatment, but did not influence spontaneous alternation performance or behavior in an elevated plus-maze test. Thus, repeated IL-2 may influence spatial working memory without affecting habituation/ attentional processes or anxiety.

Animals↗

Restoration of spontaneous exploratory behaviors with an intrathecal NMDA receptor antagonist or a PKC inhibitor in rats with acute pancreatitis.

The aim of this study was to determine the influence of a glutamate receptor antagonist or a protein kinase C (PKC) inhibitor on the central visceral nociceptive amplification process present in an experimental pancreatitis model. The acute pancreatitis model was produced by combining intraductal infusion of an irritative bile salt, glycodeoxycholic acid (GDOC), with intraperitoneal injection of a CCK analogue, caerulein, in male Sprague-Dawley rats. Exploratory activities were measured with an automated photobeam activity system and compared among different treatment groups. To confirm the inflammation, the pancreas was weighed and compared histologically with those taken from naive rats. Exploratory activity changed significantly in rats with experimental pancreatitis (i.e., rearing events, rearing time, active time, distance traveled, and total activity all were decreased; whereas resting time was increased). The inflamed pancreatic tissues were edematous, with moderate to marked acinar atrophy and inflammatory infiltrate. Intrathecal administration (at the T7-T9 spinal levels) of an NMDA receptor antagonist (D-AP5, 1 microg) or a selective PKC inhibitor (GF109203X, 0.15 microg) significantly reversed the changes in exploratory activity when compared with the vehicle-treated group of rats with experimental pancreatitis. Our results demonstrate that pancreatitis pain is the result of central pain processes that play a role in the amplification of responses to peripheral visceral input through NMDA receptor activation and PKC phosphorylation signaling pathways.

Acute Disease↗

Contrasting effects of Org 2766 and alpha-MSH on social and exploratory behavior in the rat.

Intraperitoneal injection of Org 2766 (0.01-0.4 microgram/kg) produced a dose-related increase in the number of social contacts and in the time spent in active social interaction by pairs of male rats tested in arenas with which they were familiar, but had little effect when the rats were tested in unfamiliar arenas. The increased social interaction was not accompanied by any change in motor activity. In contrast, alpha-MSH (20-200 microgram/kg) decreased the time spent in active social dose-related. Both peptides reduced exploratory head-dipping only at high doses (4-8 microgram/kg for Org 2766 and 200 microgram/kg for alpha-MSH); this change was not accompanied by a reduction in motor activity.

Adrenocorticotropic Hormone↗

[The exploratory behavior in an open field and in a burrowing chamber of rats with different predispositions to stress].

The peculiarities of oriental research behavior and correlation between activities of catecholaminergic and serotoninergic brain systems dependently on their stress resistance degree were investigated in Wistar rats. The experiments showed that resistant (R) to a sound stimulus rats differed from nonresistant (NR) ones by increased research activity under moderate stress in the open field test and by decreased research behavior level in the cell chamber test. The biochemical analysis of biogenic amines in different brain structures revealed increased norepinephrine levels in stress R rats, and increased dopamine and serotonin levels in NR ones. The findings suggest that inborn behavior regulation in animals with different stress resistance is determined by different correlations between serotonin-dopamine and norepinephrine brain systems activities.

Animals↗

Further evidence that histamine in hippocampus affects the exploratory behavior in the rat.

The effect of histamine (HA) and 3-methyl-histamine (3-MHA) in the hippocampus on hole-board behavior was studied. Male rats were microinjected stereotaxically into the hippocampus with 1 microliter of saline solution containing 9, 45 or 90 nMol of HA or 3-MHA. Five min later, all rats were tested for 5 min in a hole-board and locomotor, rearing, grooming and head-dipping activities were measured by direct observation. HA inhibited rearing and grooming at all the doses used but it affected locomotor activity only at 45 and 90 nMol doses. There was no effect on head-dipping behavior. 3-MHA instead increased locomotor and head-dipping activities at all the doses used and it did not change rearing and grooming. The present results give a further support for a physiological participation of HA in the hippocampus.

Animals↗

[Lithium oxybutyrate and the rhythmic structure of the actively exploratory behavior and body temperature in rats under constant illumination conditions].

Under constant illumination (LL 24) conditions, lithium hydroxybutyrate (LHB, daily dose 10 mg/kg, 10 days) facilitated the formation of synchronized 24-h rhythms in the active-search (open-field) behavior and body temperature variation in rats, independently of the objective drug administration time. In the dark (DD 24), LHB increased the free-running rhythms and facilitated synchronization of the internal harmonics, especially upon the drug administration in the objective p.m. phase.

Animals↗

Exploratory behavior and reaction to novelty in rats: effects of medial and lateral septal lesions.

This study was carried out to investigate whether medial septal (MS) or lateral septal (LS) lesions may differentially affect rats' ability to react to novelty or environmental change. Three types of task were used based on various sets of stimuli: visual and tactile, olfactory only, and visual only. The results showed that MS and LS lesions reduced preference for novelty, with different effects. The MS group displayed decreased exploration of both neutral and novel objects, whereas the LS group exhibited increased exploration of the objects compared with the control group. A reduced level of locomotor and rearing activity was initially seen among the MS animals. These results were compared with previous findings of behavioral changes after regional hippocampal perforant path lesions in the same test as used in this study. The comparisons imply that disruption of setal input to the hippocampal formation produces cognitive deficits different from those seen after disruption of entorhinal input.

Animals↗

Prenatal protein malnutrition affects exploratory behavior of female rats in the elevated plus-maze test.

To study the effects of prenatal protein deficiency in the exploration of the elevated plus-maze, an ethological procedure was used. Female rats were provided with 25% (control) or with 6% (low-protein) casein diets before and during pregnancy. After birth eight pups in each litter (six males and two females) were fostered to a control mother. After weaning (21 days of age) all animals received a lab chow diet until behavioral testing began at 70 days of age. Individual prenatally malnourished (n = 12) and well-nourished (n = 12) females were placed at the center of the elevated plus-maze and allowed to explore for a 5-min session. One session was given per day for 6 consecutive days. The following variables were recorded: percentage of open arm entries; percentage of time spent in open arms; total arm entries; time in the center platform; latency to first open arm entry; number of attempts to enter an open arm; number of rearings; number of head-dips. The results showed a significant effect of malnutrition on six behaviors (percent open arm entries, percent time spent in open arms, attempts to enter open arms, rearings, head-dips, and latency to first open arm entry) and a significant diet by session interaction on two behaviors (attempts to enter open arms and head-dips). These results indicate increased exploration of the open arms in prenatally malnourished as compared with well-nourished control rats, suggestive of lower anxiety and/or a higher impulsiveness in these animals.

Animals↗

GABAergic and glutamatergic modulation of exploratory behavior in the dorsomedial hypothalamus.

Systemic injection of glutamate NMDA receptor antagonists or drugs that facilitate GABA(A)-mediated neurotransmission produces anxiolytic effects. The dorsomedial hypothalamic (DMH) region is proposed to be a possible site of action of these drugs. The objective of the present study was to investigate if facilitation of GABA(A)-mediated neurotransmission or blockade of NMDA receptors in the DMH would produce anxiolytic effects in the elevated plus-maze (EPM). Seven days after surgery, male Wistar rats with unilateral cannulas in the DMH were submitted to the behavioral studies. Results showed that midazolam, a benzodiazepine anxiolytic (30-60 nmol/0.3 microl), produced a dose-dependent increase in open arm exploration without changing the number of enclosed arm entries, indicating an anxiolytic effect. This effect was antagonized by previous treatment with flumazenil, a benzodiazepine receptor antagonist (60 nmol/0.3 microl). Flumazenil alone had an anxiogenic effect, decreasing exploration of the open arms of the EPM. 2-Amino-7-phosphonoheptanoic acid (AP7), an NMDA receptor antagonist (0.2-2 nmol/0.3 microl), did not modify open arm exploration but decreased general exploratory activity. These results indicate that benzodiazepine receptors located in the DMH could modulate anxiety. Interference with NMDA receptor-mediated neurotransmission in this region, however, seems to change general exploratory activity rather than anxiety.

2-Amino-5-phosphonovalerate↗

[Effect of tuftsin on the orientation-exploratory behavior of normal white rats and against a background of pharmacologically induced disorders of the brain biogenic amine system].

The application of "hole board" method showed that the endogenic immunostimulator tetrapeptide tuftsin injected intraperitoneally in dose 0.3 mg/kg has a short-time stimulating action on the orienting reaction of rats in 5 min, though in 24 hours it suppresses the registered behavioral indexes. The pharmacological analysis of the above studied phenomenon showed that catecholaminergic and especially dopaminergic brain systems played the leading role in tuftsin effect. Tuftsin can normalize animals' behaviour disturbed by the pharmacological agents, which slightly influence the functioning of the brain dopaminergic system.

Animals↗

[A comparative study of the asymmetry in the spatial-exploratory behavior of mice in 2 populations].

In two populations of contemporary generations of non-strain mice was found a considerable shift of interhemispheric asymmetry the relative activity of the right hemisphere being increased in comparison with the known data. Quantitative evaluation and the character of this shift in the two populations were different. Changes observed are suggested to be a manifestation of adaptive response of the organism to environmental pollution.

Adaptation, Physiological↗

Iron and zinc supplementation promote motor development and exploratory behavior among Bangladeshi infants.

BACKGROUND: Iron and zinc deficiency are prevalent during infancy in low-income countries. OBJECTIVES: The objectives were to examine whether a weekly supplement of iron, zinc, iron+zinc, or a micronutrient mix (MM) of 16 vitamins and minerals would alter infant development and behavior. DESIGN: The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies. Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment (HOME) scale. In this double-blind trial, the infants were randomly assigned to 1 of 5 treatment conditions: iron (20 mg), zinc (20 mg), iron+zinc, MM (16 vitamins and minerals, including iron and zinc), or riboflavin weekly from 6 to 12 mo. Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group, with control for maternal education, HOME score, months breastfed, anemia, growth at 6 mo, and change in growth from 6 to 12 mo. RESULTS: Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development. Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement. Two-thirds of the infants were mildly anemic, no treatment effects on hemoglobin concentration were observed, and hemoglobin was not associated with measures of development or behavior. CONCLUSION: The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together.

Anemia, Iron-Deficiency↗

Role of experimental conditions in determining differences in exploratory behavior of prenatally stressed rats.

The effect of prenatal stress was determined on exploration in situations that induce different levels of fear. Dams (12) were stressed by noise and light thrice weekly on an unpredictable basis throughout pregnancy, and 12 controls were left undisturbed. The time spent by different groups of their adult offspring of both sexes in exploration was assessed during 4 min in a plus maze; large, well-lit open field (1), and open field (2) after prior exposure to a small, dark holebox. Prenatal stress resulted in a significant reduction in the number of arm entries in the plus maze and amount of time spent in the open arms. Locomotion and rearing were also reduced in Open Field 1 and 2, but these activities and hole poking were unchanged in the holebox. It is concluded that prenatal stress renders the animal more fearful to a novel, intimidating environment, which may be expressed as a suppression of exploratory activity.

Animals↗

[Effect of psychotropic substances on orienting-exploratory behavior after startling caused by acoustic stimulation].

Frightening sound stimulation induced alarm and alertness which resulted in weakening of attention to novel environment and increasing of orienting response to the source of the frightening sound. Defense motivation occurring under these conditions failed to alter with the increase of sound loudness. Tranquilizers (diazepam, chlordiazepoxide, benatyzine), antidepressants (amytriptiline, imipramine) and some neuroleptics (trifluoperazine, haloperidol) in a low doze prevented these disturbances. High doses of pentobarbital, chlorpromazine, as well as trifluoperazine and haloperidol did not prevent the mentioned consequences of emotional excitation.

Acoustic Stimulation↗

Rat exploratory behavior controlled by intracranial self-stimulation improves the study of place cell activity.

This report is limited to the description of a procedure that should help to resolve the question whether firing fields of hippocampal place cells are relatively stable or modifiable by learning. Rats implanted with lateral hypothalamic electrodes for rewarding intracranial self-stimulation (ICSS) were trained to explore a circular open field (100 cm in diameter) while their locomotion was tracked by a computerized video system which also delivers ICSS whenever the animal's exploration has met certain experimenter defined criteria. The 3 following conditions were examined. (1) Homogeneous exploration of the entire field: ICSS was delivered after the animal repeatedly visited 5 equal segments of the field (central annulus and remainders of the 4 quadrants), entered randomly located circular areas of the field, and/or traveled a criterion distance. (2) Place field contingent reward or non-reward: ICSS was delivered when the animal entered a circular area (23 cm in diameter) corresponding to the place field after a previous visit to a similar area outside the place field. These conditions were reversed in the following task. (3) Delayed reward: ICSS was delivered when the animal entered the circular area and remained in it for 2 s. Each condition was tested for 600 s or until 50 ICSS were delivered. The behavioral procedures described make it possible to propose an experimental protocol that allows examination of the same place cell under conditions of homogeneous exploration with a segment condition or randomly distributed reward and under conditions with the place field signaling reward or non-reward. The delayed reward condition increases the accuracy of the target location and allows assessment of the phasic versus tonic nature of the place cell firing.

Animals↗

Exploratory behavior, learning ability, and thyroid hormonal responses to stress in female rats rehabilitating from postnatal hypothyroidism.

Newborn female Long-Evans rats were divided into groups of normal, hypothyroid [0.1% propylthiouracil (PTU) a reversible antithyroid goitrogen in the litter's drinking water], and hypothyroid rehabilitated (PTU water from birth to day 25, normal water thereafter). The rats were tested for several adaptive behavioral tasks between 40 and 90 days of age. At day 50, serum concentration of TSH and thyroid hormones revealed no detectable amounts of T4 and a 10-fold increase in TSH in the hypothyroid rats. At the same age in the rehabilitated animals, TSH levels were still below normal, a deficit fully normalized by day 90. Normal 50-day-old rats responded to pain stress (electric footshocks) by a significant depression of serum T4 and elevation of T3 levels within 10 min of treatment, whereas the rehabilitated animals exhibited an opposite pattern of response, i.e., an increase in the circulating T4 and a decrease in T3. At 50 days of age, both hypothyroid and rehabilitated rats showed decreased exploratory activity and no habituation in the hole-board test, whereas the locomotor activity of the rehabilitated females was significantly higher than that of the normals. No differences were found in the scores of passive avoidance learning (one trial step-through) among the three groups. Similarly, the rate of acquisition of the active one-way conditioned avoidance response (CAR) of the hypothyroid and rehabilitated rats did not differ significantly from that of the controls. However, the hypothyroid rats required significantly more unconditioned stimuli (footshocks) to acquire CAR and showed longer response latency and less intertrial responses. Although the hypothyroid rats showed no extinction of CAR, the rehabilitated rats were capable of extinction to an extent indistinguishable from normal rats. But compared with the normal animals, the rehabilitated rats showed significantly higher intertrial activity during both the acquisition and extinction phases of CAR.

Animals↗

[Neurochemical mechanisms of the involvement of sensorimotor cortex neurons in food and orienting-exploratory behavior].

Reactions of individual neurons to electrical stimulation of motivational areas of the lateral hypothalamus were studied in the somatosensory cortex of alert rabbits during micro. iontophoretic application of acetylcholine, norepinephrine or cycloheximide. The former two drugs altered equally the neuron reactions both on weak (inducing an orienting response) and strong stimulation (causing feeding behaviour). The latter drug also affected the neuron reactions. The feeding and orienting responses seem to be actualized through a specific peptide synthesis in the somatosensory cortex's neurons altering their sensitivity to neurotransmitters.

Acetylcholine↗