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PubMed2006

Behavioral profiles and stress-induced corticosteroid secretion in male Wistar rats subjected to short and prolonged periods of maternal separation.

Early life experiences are important for the development of neurobiobehavioral mechanisms and subsequent establishment of mental functions. In experimental animals, early life experiences can be studied using the maternal separation model. Maternal separation has been described to induce neurobiological changes and thus affect brain function, mental state and behavior. We have established a protocol in order to study the effects of repeated short and prolonged periods of maternal separation during the postnatal period on adult neurochemistry, voluntary ethanol intake and behavior. In the present experiment, we focus on the long-term effects of maternal separation on exploration and risk assessment behavior as well corticosteroid secretion. Rat pups were assigned to 15 min (MS15) or 360 min (MS360) of daily maternal separation and normal animal facility rearing (AFR) during postnatal days 1-21. To establish the adult behavioral profile in male rats, three tests were used: the Concentric Square Field (CSF), the Open Field (OF) and the Elevated Plus-maze (EPM). No differences between the three experimental groups were found in the traditional OF and EPM tests. The CSF test indicated that the MS360 rats were more explorative and expressed an altered risk assessment and risk-taking profile. In response to a restraint stress, MS360 rats had a blunted corticosterone release in contrast to MS15 and AFR rats. In contrast to previous results, the outcome of the present investigation does not support the notion that a prolonged period of maternal separation results in an adult phenotype characterized by an increased emotional reactivity.

Animals↗
PubMed2000

Male mice lacking the gastrin-releasing peptide receptor (GRP-R) display elevated preference for conspecific odors and increased social investigatory behaviors.

Previously, we generated gastrin-releasing peptide receptor null mutant mice (GRP-R-deficient mice), and found that these animals displayed increased non-aggressive social responses in an ordinary social interaction test using a resident-intruder method. In the present study, we examined in more detail the social behaviors of GRP-R-deficient male mice. In social interaction tests, GRP-R-deficient mice showed more social responses, such as sniffing and nosing, relative to wild-type mice, and similar results were obtained whether GRP-R-deficient mice served as intruders or residents. In the same way, they showed more contact behaviors toward an anesthetized conspecific, and less locomotor activity than wild-type mice in a social investigation test toward an anesthetized male mouse. Since olfactory systems play important roles in the social behavior of rodents, olfactory preference tests were conducted in order to evaluate the olfactory properties of GRP-R-deficient mice. The results suggest that no differences exist between wild-type mice and GRP-R-deficient mice in the preference between a novel sawdust odor and their own odor, or that of other male mice. However, GRP-R-deficient mice preferred the odor of other male mice to their own, in contrast to wild-type mice. Furthermore, the preferences of GRP-R-deficient and wild-type mice were not disrupted by intraperitoneal infusion of diazepam (1.5 mg/kg). These results indicate that neither the motion, nor the behavior of conspecifics, nor reduced anxiety lead to the increased non-aggressive social responses and/or social investigatory behaviors in GRP-R-deficient mice. Rather, these latter behaviors may be a consequence of altered cognition of conspecific odors in the mutant mice.

Aggression↗
PubMed2000

What is the significance of gamma wave activity in the pyriform cortex?

The relations between behavior, olfactory input and bursts of gamma wave activity (roughly 30-90 Hz) in the pyriform cortex were studied in freely moving rats. Olfactory input was measured by recording the negative (depolarizing) potentials which occur in the olfactory mucosa during inspiration. Low levels of pyriform gamma activity were associated with spontaneous apnea and slightly higher levels were associated with vigorous sniffing. Intermediate levels of gamma activity occurred during rhythmical breathing during alert immobility, walking, eating, and grooming. High amplitude bursts of gamma activity occurred during very deep breathing during sighing and vocalization. Closing one nostril resulted in the ipsilateral disappearance of pyriform gamma wave bursts, even during vocalization, but contralateral gamma wave activity persisted. It is concluded that pyriform gamma wave activity is entirely dependent on olfactory input and that previously reported relations to conditioning, arousal, motivation, etc., are indirect effects of variations in the pattern of air flow in the upper airway.

Animals↗
PubMed2001

Changes in defensive behaviors following olfactory bulbectomy in male and female rats.

The present study examined if olfactory bulbectomy (OBX) altered defensive behaviors on the elevated plus-maze and the open-field differently in male and female rats. Similar increases in defensive behaviors in male and female rats were observed in both tests following OBX. No significant correlations were detected between defensive behaviors and activity, supporting the hypothesis that some behavioral changes following OBX may be due to decreased defensive behaviors and not increased activity.

Aggression↗
PubMed1998

Reaction of sleep-wakefulness cycle to stress is related to differences in hypothalamo-pituitary-adrenal axis reactivity in rat.

Acute stress is known to modify sleep-wakefulness cycle, although with considerable interindividual differences. The origin of these individual differences remains unknown. One possibility is an involvement of the hypothalamo-pituitary-adrenal axis (HPA), as its reactivity is correlated with an individual's behavioral reactivity to stress, and it is known to influence the sleep-wakefulness cycle. The present study was designed to analyze relationships between natural differences in behavioral reactivity to stress associated with differential HPA reactivity and stress-induced changes in sleep-wakefulness. Adult rats were classified into two sub-groups according to their locomotor reactivity to a mild stress (novel environment): the 'low responders (LR)' and the 'high responders (HR)' animals exhibited different glucocorticoid secretion in response to stress. We show that immobilization stress induced an increase in wakefulness in LR animals and a decrease in wakefulness in HR animals. On the other hand, paradoxical sleep was increased in both LR and HR animals. Moreover, we observed that LR animals slept more than the HR animals, whereas the two groups had similar levels of paradoxical sleep. These results indicate that the response of the sleep-wakefulness cycle to stress is related to the behavioral reactivity to stress, in turn governed by the individual's reactivity of the HPA axis. The involvement of dopaminergic mechanisms is discussed.

Animals↗
PubMed1998

Interleukin-2 and -6 induce behavioral-activating effects in mice.

Interleukin (IL)-1, IL-2 and IL-6 influence central monoamine activity in a cytokine-specific manner. We demonstrated that whereas IL-2 increased hypothalamic and hippocampal norepinephrine (NE) utilization, and DA turnover in the prefrontal cortex, IL-6 induced profound elevations of serotonin (5-HT) and mesocortical dopamine (DA) activity in the hippocampus and prefrontal cortex [S. Zalcman, J.M. Green-Johnson, L. Murray, D.M. Nance, D.G. Dyck, H. Anisman, A. H. Greenberg, Cytokine-specific central monoamine alterations following IL-1, -2 and -6 administration, Brain Res. 643 (1994) 40-49]. IL-1, in contrast, induced a wide range of central monoamine alterations. We presently report that these cytokines also differentially influence behavior. Profound reductions in non-ambulatory and ambulatory exploration were induced in BALB/c mice following IL-1 administration. In contrast, IL-2-treated mice displayed significant increases in the time spent engaged in non-ambulatory exploration, digging, rearing (particularly the number of free rears), and in the investigation of a novel stimulus (i.e., increased number and duration of stimulus contacts). IL-6-treated mice, moreover, exhibited significant increases in the time spent engaged in ambulatory exploration, digging and rearing (particularly the number of free rears, which tended to be of short duration). Modest increases in locomotion and grooming were also observed in IL-6-treated animals. Plasma corticosterone levels did not vary significantly as a function of IL-6 treatment. Hence, cytokine-specific behavioral-activating effects were induced following administration of IL-2 and IL-6. We suggest that these effects have adaptive significance and relevance to sickness behavior; however, pathological outcomes (e.g., schizophrenia, anxious-like states, anxious depression, motor abnormalities) could develop should these cytokines be overproduced or dysregulated.

Adaptation, Physiological↗
PubMed2001

Opposite effects of substance P fragments C (anxiogenic) and N (anxiolytic) injected into dorsal periaqueductal gray.

Recent findings implicating neurokinins in the expression of anxiety-like behaviors have stimulated interest in the participation of these neuropeptides in the dorsal periaqueductal gray matter (dPAG), one of the main output regions of the brainstem for the expression of defense reaction. Studies on the behavior of rats submitted to the elevated plus-maze test in this laboratory have shown that microinjections of substance P into the dorsal periaqueductal gray produce anxiogenic-like effects. Now, we analyze what portion of the molecule of substance P is responsible for these effects through the examination of the action of its C- and N-terminus fragments (6-11 and 1-7) in the elevated plus-maze. We also investigated whether these effects are influenced by prior treatment with the tachykinin NK(1) receptor antagonist 17-beta-hydroxy-17-alpha-ethynyl-5alpha-androstanol[3,2-b]pyrimido[1,2-a]benzimidazole (WIN51,708). To this end, rats were implanted with a cannula in the dorsal periaqueductal gray and injected 1 week later with equimolar doses (17.5 and 35 pmol) of either C- or N-fragments of substance P and tested in the elevated plus-maze. The results show that the C-terminal fragment has an anxiogenic profile of effects, including reduction in the number of entries and time spent in the open arms of the maze, plus increases in scanning, stretched-attend posture, head dipping and flat-back approach. On the other hand, the N-terminal fragment produced opposite effects, namely, an increase in the number of entries and time spent in the open arms of the maze accompanied by an increase in end-arm activity, rearing and head dipping. The tachykinin NK(1) receptor antagonist WIN51,708 (20 mg/kg, i.p.) inhibited the effects of the carboxy-terminal of substance P while it did not change the effects of the N-terminal fragment. Microinjection of WIN51,708 (20 mg/kg, i.p.), by its own, did not produce any significant effects. Therefore, the results indicate that the anxiogenic effects of substance P injected into the dorsal periaqueductal gray are encoded by its carboxy-terminal sequence and due to its action on tachykinin NK(1) receptors.

Analysis of Variance↗
PubMedDate not supplied

Differential analysis of behavior and diazepam-induced alterations in C57BL/6N and BALB/c mice using the modified hole board test.

A variety of test procedures are used in preclinical research on behavioral pharmacology and to dissociate behavioral differences or pharmacologically induced behavioral alterations several independent tests are usually performed. In the present study we introduce a modified hole board procedure for mice which allows us to investigate a variety of behavioral parameters such as anxiety, risk assessment, exploration, locomotion, food-intake inhibition, novelty seeking, and arousal by using only one test. The modified hole board was established by investigating the behavior of two inbred mouse strains, C57BL/6 and BALB. Significant differences in terms of locomotor activity, general exploration, and other parameters were found. Moreover, strain-specific exploration strategies could be detected in the modified hole board. Further, the test was validated by investigating the effects of diazepam as standard anxiolytic on the behavior in both mouse strains. Acute administration of diazepam (1 and 3 mg/kg) induced strong sedative effects in a dose-dependent manner in C57BL/6 mice. In BALB mice, the lower dosage of diazepam showed an activating and anxiolytic action while the 3 mg dosage revealed a slight sedative but still anxiolytic effect in these animals. Taken together, the results demonstrate that the modified hole board enables to differentially investigate behavioral phenotypes and also pharmacologically-induced behavioral alterations in mice. Therefore, this new strategy allows to reduce the number of experimental animals and the time needed, thus, representing an effective screening-tool for behavioral investigations.

Animals↗
PubMedDate not supplied

Temperament and character inventory (TCI) and depression.

Although several studies have assessed the relationships between the temperament dimensions of the Cloninger model of personality and depression, little is known about the role played by the character dimensions proposed by the seven-factor model of Cloninger in depression. In this study, the relationships between the Temperament and Character Inventory (TCI) and depression were examined in a sample of 40 major depressive patients and 40 healthy controls. Depressed patients exhibit higher harm avoidance and self-transcendence scores as well as lower self-directedness and cooperativeness scores as compared to healthy controls. However, the three other dimensions do not differ between depressive patients and controls. Among the depressive group, harm avoidance, self-directedness and cooperativeness dimensions are related to the severity of depression as assessed by the Hamilton scale. This study confirms the state dependence of the harm avoidance dimension and suggests a relationship between the character dimensions of the Cloninger model and depression.

Adult↗
PubMed1997

The effects of isolation-rearing on preference by rats for a novel environment.

In the previous paper isolation-reared rats exhibited enhanced environmental neophobia under some conditions in an open-field. However, previous work has shown that isolation-reared rats have greater preferences for a novel environment in a dimly lit enclosed box. The hypothesis examined in the present experiments was that manipulation of the intrinsic aversive qualities of such an environment, by altering lighting conditions, could reverse the preference which isolation-reared rats exhibit for a novel chamber. When preference for a novel chamber was examined in a non-aversive environment in Experiment 1, isolation-reared rats exhibited a preference for a novel environment which was enhanced compared to social controls. When tested under more aversive white light conditions in Experiment 2, no differences in novelty preference were observed between isolation-reared and socially reared rats. Thus, the increased sensitivity to novel environments by isolation-reared rats appears to be critically dependent on the arousing or aversive properties of the testing conditions.

Animals↗
PubMed2002

Taking the rough with the smooth: foraging for particulate food in continuous time.

This paper describes the development of the general dynamical model of foraging developed by Ollason (1980, Theoret. Popul. Biol. 18, 44-65) to predict foraging for particulate food in three different types of environment. In an environment containing particles of different types of food, the model predicts the selection of an approximately optimal diet; in an environment in which the particles occur in patches, the model predicts a time budget of patch occupancy that approximates to the optimal time budget; and in an environment containing patches of particles that regenerate by the addition of particles of food at constant rates, the model predicts that animals will dispose themselves among the patches approximately as predicted by the ideal free distribution. Where the predictions of the model depart from the predictions of optimal foraging theory, they are qualitatively similar to the observed departures of the behaviour of real animals from the predictions of optimal foraging theory. The model provides a general representation of the foraging decisions of animals whether they feed strictly continuously or discontinuously on particles of food, and does so without explicit reference to optimization processes.

Animals↗
PubMed2002

Object preference and nicotine consumption in rats with high vs. low rearing activity in a novel open field.

Our previous work has shown that normal male wistar rats can differ systematically with respect to rearing activity in a novel open field: animals with high rearing activity (HRA rats) differed from those with low rearing activity (LRA rats) in dopaminergic and cholinergic brain activity, as well as in their behavioral responsiveness to a cholinergic antagonist, but not in measures of anxiety in the elevated plus-maze. Here, we tested (a) whether HRA vs. LRA reflects responsiveness to novelty, (b) whether such rats voluntarily consume different amounts of the cholinergic agonist nicotine and (c) whether these measures are related to those of anxiety in the plus-maze. Using a novel object test, we found that HRA showed a trend for more object exploration than LRA rats when confronted with two identical novel objects in a familiar open field. When subsequently confronted with a familiar vs. a new object, HRA rats showed substantially more exploration of the new but not of the familiar object than LRA rats. In a subsequent test, HRA vs. LRA rats did not differ in voluntary or forced consumption of oral nicotine, or water. In contrast to rearing activity in a novel open field, measures of anxiety in the plus-maze were neither related to behavior in the novel object test nor to voluntary oral consumption of nicotine, or water. Among others, these data are discussed with respect to dopaminergic and cholinergic forebrain mechanisms, which have previously been found to differ between HRA and LRA rats. Since forebrain dopamine and acetylcholine functions are critical for novelty processing, we suggest that they are also important for the differential behavioral patterns of HRA and LRA rats in the open field, and in the novel object test.

Animals↗
PubMed1984

Caffeine and nicotine: differential effects on ambulation, rearing and wheelrunning.

Male Sprague Dawley rats were tested for open field ambulation and rearing, and for wheelrunning, following repeated injections of either caffeine or nicotine, given according to a Latin Square design. Caffeine enhanced ambulation and rearing at 5 and 15 mg/kg, IP, and increased wheelrunning with 15 and 45 mg/kg. Nicotine (0.63 mg/kg) also enhanced ambulation, but not rearing, and depressed wheelrunning during the first 20 min of testing. Caffeine's enhancement of wheelrunning was not significant during the first two drug administrations. Results suggest that caffeine and nicotine affect activity via different neuropharmacological mechanisms. Previous experience with these drugs may modulate animals' reactivity to them.

Animals↗
PubMed1997

Tolerance develops to the spatial learning deficit produced by diazepam in rats.

The present experiment sought to determine in rats if 1) tolerance develops to the amnesic effect of diazepam after chronic treatment, 2) the sedative and amnesic effects of diazepam can be dissociated via differential rates of tolerance development, and 3) withdrawal from long-term diazepam treatment affects mnemonic processes. Rats were given diazepam (3 mg/kg) acutely or chronically for 5, 15, or 30 d prior to behavioral testing. Sedation was assessed as exploratory activity in an open field and amnesia was assessed as spatial learning in the Morris water maze. Tolerance to the sedative effect of diazepam was exhibited after 5 d pretreatment whereas tolerance to the amnesic effect of diazepam was exhibited only after 30 d pretreatment. Withdrawal from diazepam produced a transitory and mild disruption of spatial learning. The data demonstrate 1) tolerance can develop to the amnesic effect of diazepam with extended treatment, 2) the sedative and amnesic effects of diazepam are largely independent, and 3) withdrawal from chronic diazepam treatment can retard optimal learning.

Amnesia↗
PubMed1998

Nijmegen high and low responders to novelty: a new tool in the search after the neurobiology of drug abuse liability.

Knowledge about the differences in structure, function, and reactivity of the brain and body between Nijmegen high responders to novelty and Nijmegen low responders to novelty may help us to understand which factors give rise to the vulnerability and/or susceptibility to drugs of abuse. For that purpose, this contribution provides a short overview of the outcome of the available studies on Nijmegen high responders to novelty and Nijmegen low responders to novelty. These animals can be selected using three major behavioral paradigms: (a) the open-field test (which allows the separation of high and low responders to novelty); (n) the intruder test (which allows the separation of fleeing and nonfleeing rats); (c) the apomorphine test (which allows the separation of apomorphine-susceptible and apomorphine-unsusceptible rats). Data to date suggest that the same traits have been selected by all three paradigms, and point to the hypothesis that the neurochemical state of the nucleus accumbens directs the sensitivity to drugs of abuse. In addition, recent evidence suggests that the sensitivity to the psychostimulant and/or reinforcing effects of dexamphetamine and ethanol is smaller in HR than in LR under certain experimental conditions, whereas the reverse is found when different experimental conditions are chosen. The data all together lay the foundation for the overall hypothesis that there are three factors ultimately determining the individual-specific sensitivity to drug of abuse: (a) the genetic background that predisposes an individual to become a HR or a LR, (b) early postnatal factors that direct the phenotypic expression of a particular genotype at adult age, and (c) the degree of stress during exposure to the drug of abuse. Further testing of this hypothesis may provide important information about the factors that contribute to individual differences in vulnerability to drugs of abuse.

Animals↗
PubMed1998

Responses of Swiss-Webster mice to repeated plus-maze experience: further evidence for a qualitative shift in emotional state?

Behavioral, endocrinological, and pharmacological data suggest that the emotional response of rodents to the elevated plus-maze alters as a function of prior test experience. In the present study, 74 intact male Swiss-Webster mice were exposed to the plus-maze for 5 min on each of 3 consecutive days, with all test sessions recorded on videotape. Behavior patterns for each trial were scored using ethological analysis software and the resultant database subjected to a number of statistical treatments. Analysis of full session profiles (i.e., 5 min total scores) showed that a single prior undrugged experience of the maze increases behavioral indices of anxiety and that these alterations are either maintained or further enhanced on subsequent trials. Furthermore, the behavioral profile evident by trial 3 was largely unchanged when animals were reexposed to the maze 10 days later. More detailed (i.e., min by min) examination of behavior patterns within and between trials demonstrated that unambiguous open arm avoidance is acquired by the third minute of trial 1, and that the behavioral profile evident by the end of trial 1 is (a) markedly different to that seen at the beginning of that trial, and (b) generally maintained or even accentuated on trials 2 and 3. The implied impact of prior test experience on future behavioral strategy in the maze was strongly supported by a series of factor analyses. Thus, while the factor associations of vertical activity and directed exploration remained constant across trials, trial 2 and 3 anxiety measures loaded on a separate factor to that loading trial 1 anxiety measures. A similar trial 1 vs. trials 2 and 3 dissociation was observed for measures of locomotor activity. Although the present findings are consistent with the proposal that prior test experience produces a qualitative shift in emotional response to the elevated plus-maze, the precise basis for this change as well as its full significance for our understanding of anxiety-related processes remain to be determined.

Animals↗