Free-Radical Lipid Oxidation in the Brains of Active and Passive Rats during the Development of Post-Stress Depression

Free-radical lipid oxidation was studied in the cerebral cortex, striatum, hippocampus, and hypothalamus of KHA and KLA rats (Koltushi High and Low Avoidance) during the development of post-stress depression. After unavoidable emotional-pain exposure, changes in the free-radical oxidation of lipids were phasic in nature and had a clear structural specificity in the early phases. During the maximum development of depression, the most marked impairments to lipid peroxidation were seen in KHA rats in the striatum and hippocampus, while the greatest changes in KLA rats were seen in the striatum and hypothalamus. These data support the important role of the initial behavioral strategy in the pathogenetic mechanisms forming post-stress psychopathology. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 5, pp. 592–597, May, 2008.     

Involvement of Dopaminergic Processes in the Striatum during the Effects of Corticoliberin on the Behavior of Active and Passive Rats

The effects of intranasal corticoliberin on behavior in the open field test were studied in rats with active and passive behavioral strategies (lines KHA and KLA); levels of dopamine and noradrenaline and their metabolites were measured in the striatum and hypothalamus. In KLA rats, administration of the neurohormone led to increases in motor and investigative activity, while decreases were seen in KHA rats. There were no interline differences in catecholamine levels in the hypothalamus, while dopamine levels in the KLA striatum nearly doubled and metabolite levels (DOPAC, HVA) were significantly lower than in KHA rats. Corticoliberin increased dopamine and noradrenaline levels in the hypothalamus of both rat lines, with significant decreases in the striatum. This decrease was more marked in KLA rats, probably due to the faster metabolism of transmitters in the presence of neurohormones, as indicated by the increase in metabolite levels in this structure.     

Characteristics of the Behavior and Stress-Reactivity of the Hypophyseal-Adrenal System in Prenatally Stressed Rats

The effects of daily 1-h immobilization of female rats from days 15 to 18 of pregnancy on the levels of anxiety, orientational-investigative activity in an open field test, and the dynamics of the stress response of the hypophyseal-adrenal system were studied in the male and female adult offspring of these rats. Maternal stress was found to induce significant reductions in the level of orientational-investigative activity of females in the stage of diestrus, and to increase anxiety as measured in an elevated cross maze. Prenatally stressed males, conversely, had decreased levels of anxiety, and behavior in the open field test was virtually unaltered. As a result, prenatally stressed rats showed smoothing out of the intergender differences in these forms of behavior, seen in control animals in normal conditions. Prenatal stress had a significant influence on the dynamics of the stress response of the hypophyseal-adrenal system in males and females; males showed impairment of the feedback control of this system in conditions of stress activation, while females showed significant increases in the maximum level of adrenal corticosterone secretion into the blood in response to immobilization lasting 20 min. These data provide evidence that maternal stress has significant influences on behavior and the stress response in both male and female rats.     

Activity of the Hypothalamic-Pituitary-Adrenocortical System and Sleep-Wake Cycle in Rats with Acute Systemic Inflammation

Activity of the hypothalamic-pituitary-adrenocortical system and EEG characteristics of the sleep-wake cycle were studied on adult male Wistar rats with acute inflammation produced by bacterial lipopolysaccharide in a dose of 250 g/100 g body weight. Blood concentrations of adrenocorticotropic hormone and corticosterone increased by 6 and 10 times, respectively, 30 min after lipopolysaccharide administration and peaked 2 hours after challenge. In this period the sleep-wake cycle underwent the most pronounced changes that could be attributed to the stupor-like state observed in clinical practice. It was manifested in dissociation between locomotor activity of animals and EEG characteristics, suppression of EEG components in slow-wave sleep, increase in the number of -waves, and decrease in the number of -waves in EEG. In the present work we consider possible mechanisms of temporal relationships between activity of the hypothalamic-pituitary-adrenocortical system and disorganization of the sleep-wake cycle during acute systemic inflammation.     

Interhemisphere Asymmetry of the Hippocampus and Neocortex as a Correlate of the Active and Passive Behavioral Strategies in Emotionally Negative Situations

Cross-correlation histograms were used to study the interhemisphere interactions of cells in bilateral leads from the parietal and sensorimotor areas of the neocortex and hippocampal field CA1 in groups of rabbits with active and passive behavioral strategies in an open field test. Passive rabbits showed asymmetry in the bilateral interaction: with right-sided dominance in the neocortex and left-sided dominance in the hippocampus. Active animals, conversely, showed left-hemisphere dominance in the neocortex, with no asymmetry in the hippocampus. Brain lateralization was apparent as motor asymmetry in relation to preference for right or left turns in the open field: passive rabbits showed a relative preference for left turns and active animals for right turns. In all animals, systemic administration of the GABA_B receptor agonist phenibut, which decreases behavioral reactivity to emotionally significant stimuli, eliminated the interhemisphere asymmetry seen in normal conditions in emotionally negative situations. These results provide evidence that interhemisphere asymmetry at the levels of the neocortex and hippocampus is linked with the individual-typological characteristics of the animals and reflects readiness for the most typical types of behavioral responding in active and passive animals.     

Effects of Impairments to Glucocorticoid Receptor Mechanisms in Early Ontogeny on the Activity of the Hypophyseal-Adrenocortical System and Behavior in Male Rats

The effects of treatment of rats with hydrocortisone (1 mg/100 g) or the glucocorticoid receptor blocker RU38486 (1 mg/100 g) from day 1 to day 5 of life on changes in the dynamics of the stress response of the hypophyseal-adrenocortical system (HAS), orientational-investigative activity, and anxiety in immature and adult male rats were studied. Excess glucocorticoid hormones during the early neonatal period was found to increase orientational-investigative activity and the level of anxiety in immature males without altering the functional activity of the HAS or behavior in adult rats. Conversely, impairment of glucocorticoid receptor mechanisms in brain structures in neonatal rats led to decreased feedback efficiency in the regulation of the HAS, decreases in motor activity, and increases in anxiety levels in conditions of contextual novelty, which was most clearly apparent at adult age. It is suggested that rearrangement of glucocorticoid reception during the neonatal period of development is among the causes of the various hormonal and behavioral impairments in adult individuals.     

Responses of the Hypophyseal-Adrenal System to Stress and Immune Stimuli in Gray Rats Selected for Behavior

The characteristics of the responses of the hypothalamo-hypophyseal-adrenal system to restriction stress and administration of lipopolysaccharide and interleukin-2 were studied in gray rats selected for the maintenance and absence of aggressive behavior in relation to humans. These experiments demonstrated decreased levels of corticosterone and ACTH in the plasma of tame rats in restriction stress and after administration of lipopolysaccharide as compared with non-tame rats. After administration of interleukin-2, the corticosterone level was identical in both groups of animals, though it reached the basal level in tame rats more quickly than in rats selected for maintaining aggressive behavior. Thus, selection of gray rats for tame behavior induces not only decreases in the responses of the hypophyseal-adrenal system to restriction stress, but also changes its response to immune stimuli and also, perhaps, its interaction with the immune system.     

Behavioral Reactivity to Social and Nonsocial Stimulations: A Multivariate Analysis of Six Inbred Rat Strains

Male rats from six inbred rat strains (Spontaneously Hypertensive Rat, Wistar Kyoto, Brown Norway, Wistar Furth, Fischer 344, and Lewis) have been compared for their behavioral reactivity when placed in several nonsocial (elevated plus-maze, open field) and social (social interaction in aversive and neutral environment, resident–intruder test, chronic social stress) settings. In addition, a factorial analysis was performed to assess how the variables measured in these different tests related to each other. Besides significant strain-related differences in all tests, the factorial analysis showed that, in nonsocial environments, the strains contrasted essentially along two independent behavioral traits, the propensity to approach or avoid an aversive stimulus and general motor activity in novel environments (two indices of emotionality). In the social settings, marked interstrain differences were observed regarding the expression of aggressive behaviors but these differences were not related to the respective levels on the two nonsocial components of reactivity. Furthermore, large genetic differences were observed in variations of body weight induced by a chronic social stressor paradigm. The factorial analysis suggested a lack of relationship between the effect of social stressors on body weight and the measures of emotionality and general activity obtained in the nonsocial tests. Conversely, these variations were influenced by the levels of aggressiveness and sociability. Taken together, these results show (i) that the behavioral variability observed in rats, in social and nonsocial environments, is influenced by genetic factors and (ii) that the behavioral reactivity to social stimulations is a specific feature, dissociable from the levels of the different components of emotionality (approach/avoidance and general activity) as evaluated by the behavioral responses to nonsocial settings.     

Heart Rate Reactivity and Type A Behavior as Modifiers of Physiological Response to Active and Passive Coping

We examined the long term predictivity of heart rate reactivity (HRR) and its relation to cardiovascular and biochemical activity during rest and during tasks requiring active and passive coping. HRR was determined in 28 young men by measuring peak heart rate change to cold pressor one year after performing tasks eliciting active and passive coping. Heart rate change to cold pressor was significantly correlated with change to active coping (r= .65, p<.01) and to passive coping (r= .53, p<.01). Responses to the tasks were equivalent for Type A and B subjects. On the other hand, high HRRs were significantly more reactive than low HRRs with the effect being most apparent during active coping. HRR appeared to be a trait stable over one year which predicted enhanced cardiac, neuroendocrine, and neuromuscular response.     

Psychosocial Interventions for Bipolar Disorder: Perspective From the Behavioral Approach System (BAS) Dysregulation Theory

Research has emerged providing consistent support for the behavioral approach system (BAS) dysregulation theory of bipolar disorder. The objective of the current article was to examine the extent to which findings from the BAS dysregulation theory can inform psychosocial interventions for bipolar disorder. Toward this end, we first provide an overview of the BAS dysregulation theory. Second, we review extant research on psychosocial interventions for bipolar disorder. And, third, we discuss means by which research and theory in line with the BAS dysregulation model can inform psychosocial interventions for bipolar disorder. Particular attention is given to the clinical implications of research, suggesting that bipolar disorder is characterized by high drive/incentive motivation, ambitious goal-setting, and perfectionism in the achievement domain.     

The Effects of Novelty and Behavioral Stereotype on the Development of Amnesia in Mice

The aim of the present study was to analyze the significance of the interaction between the basic behavioral strategy, the extinction of the novelty of information, and the efficacy of amnesia-inducing influences. Using a combination of training to passive avoidance with holding the animal in the unsafe sector of the apparatus, comparative analysis was performed of the reproduction of a memory trace in aggressive and submissive mice of line C57BL/6J with and without six sessions of familiarization with the apparatus. These experiments showed that preliminary habituation prevented the development of amnesia in submissive but not aggressive individuals. The cause of these differences in the effects of preexposure on the development of amnesia involves the selectivity of the process of extinction of information novelty characteristic for the behavioral stereotype.     

Individual Differences in Plasma Catecholamine and Corticosterone Stress Responses of Wild-Type Rats: Relationship With Aggression

Plasma noradrenaline (NA), adrenaline (A), and corticosterone (CS) responses to social and nonsocial stressors were studied in male members of a strain of wild-type rats, widely differing in their level of aggression. The aggressiveness was preliminarily established by measuring the latency time to attack (ALT) a male intruder in a standard resident-intruder test. Animals were then provided with a jugular vein cannula for blood sampling during stress exposure. Implanted rats were randomly assigned to 3 experimental treatments: social stress (defeat experience, SD), nonsocial stress (presentation of a shock-prod, SP) and control (animals undisturbed in their home cages, CTR). A significant correlation was found between ALT and the amount of time spent in burying the probe in SP rats: the more aggressive the animal, the higher the rate of burying behavior. SD induced a much stronger effect on plasma NA, A, and CS concentrations than SP. A significant negative correlation was found between ALT scores and values of the area under the response time curve for NA and A, in both SD and SP situations: the more aggressive the animal, the higher the catecholaminergic reactivity to the stressors. On the contrary, no evidence of a correlation between aggressiveness and plasma corticosterone responses was found, neither in SD nor in SP rats. These findings in an unselected strain of wild-type rats confirmed that an aggressive/active coping strategy is associated with a high sympathetic-adrenomedullary activation and support the concept of individual differentiation in coping styles as a coherent set of behavioral and neuroendocrine characteristics.     

Adaptive Behavior in Active and Passive Rats after Intranasal Administration of Corticotrophin-Releasing Hormone

Rats with high (KHA) and low (KLA) rates of acquiring active avoidance reflexes were used to study the effects of intranasal administration of corticotrophin-releasing hormone on orientational-investigative behavior in an open field and anxiety in an elevated cross maze. Administration of the neurohormone induced opposite changes in the behavior of the rats of these lines in the two tests. In KLA rats, movement and investigative activity increased, while in KHA rats these behaviors decreased. In the elevated maze, KLA rats, unlike KHA rats, showed increases in the time spent in the open arms, which was evidence for a decrease in anxiety in these animals. Thus, intranasal hormone administration completely reproduced the effects seen after administration into the striatum. It is suggested that corticotrophin-releasing hormone is an endogenous factor for the detailed and appropriate correction of adaptive behavior.     

Plasma ACTH Levels During Early, Two-Way Avoidance Acquisition in High- and Low-Avoidance Rats (Hatano Strains)

Having successfully bred for high- and low-avoidance rats (HAA and LAA, respectively) on a shuttlebox task, we performed three experiments designed to identify factors which might be related to the phenotypic differences seen in avoidance behavior. In experiment 1, shuttlebox behavior was measured to determine whether the phenotypic difference was activity related. In terms of intertrial responses, there was no difference between HAA and LAA rats in locomotor activity during the conditioning process. Experiment 2 compared adrenal weights of HAA and LAA rats at 11 weeks of age. The observation that the adrenal glands were heavier in HAA than in LAA rats suggested that these strains might differ in aspects of endocrine response. In experiment 3, plasma levels of ACTH and corticosterone were determined during early escape/avoidance acquisition in the shuttlebox. Plasma levels of ACTH after the shuttlebox testing were higher in HAA than in LAA rats. There was no difference between the two strains in plasma levels of corticosterone after testing, possibly due to a ceiling effect. These results suggest that the phenotypic differences in the acquisition of avoidance behavior of HAA and LAA rats may be related to different endocrine responses, rather than to locomotor activity.