Morpho-functional alterations of the adrenal cortex in rats with active and passive strategy of adaptive behavior

In rats with the active (KHA strain) and passive (KLA strain) coping strategies, a post-stress depression develops respectfully on the 1st or 10th day after the inescapable stress. The present study revealed an increase of adrenal weight and blood corticosterone levels on a day following the inescapable stress, as well as marked fluctuations of blood glucose in one and five days post-stress in KHA rats. By the 10th day, these indices returned their basal levels. In contrast, the stress reactivity of KLA rats was lower in all terms and their corticosterone levels remained reduced on the 10th day after stress. In KLA rats, the fasciculate zone was reduced but reticulated zone grew in Ith day following the stress, while in KHA rats the inescapable stress resulted in growth fasciculate zone and concomitant reduction of reticulate zone, both evident on the 10th post-stress day. The data indicate that the development of post-stress depression in KLA rats is probably associated with exhaustion of adrenocortical function.     

The reactivity of the hypophyseal-adrenal system in rats with different forms of adaptive behavioral pathology]

The dexamethasone suppression test (DST) was applied to male Wistar rats with different models of depression: group with the learned helplessness, group with informational neurosis provided by time-deficit conditioned avoidance training, as well as groups of rats of two strains selected for low (KLA)--and high (KHA) avoidance learning. The pre-dexamethasone basal and stress-induced corticosterone levels were similar in intact rats and those exposed to inescapable shock. The dexamethasone administration (5 mkg/kg) failed to decrease the serum corticosterone level in rats with learned helplessness. The informational neurosis increased significantly the basal corticosterone level and decreased the stress response. Serum corticosterone levels were similar in KLA and KHA rats. These results give evidence that two stress-induced rat models of depression with similar behavioural disturbances (reduction of escape/avoidance reactions) exhibit marked differences in the activity of hypothalamo-pituitary-adrenal (HPA) axis.     

Dynamics of hypothalamic CRH immune reactivity in active and passive rats in the course of development of behavioural depression

A possible relation between activity of the main CRH-producing centers of hypothalamus and depressive-like behavior of animals was studied. We used genetically selected strains--KHA (Koltushi High Avoidance) and KLA (Koltushi Low Avoidance) rats, demonstrating active and passive strategy of adaptive behavior in novelty situaltions, respectively. Rats were exposed to inescapable stress to develop a "learned helplessness". We observed considerable differences between two strains of animals in CRH-expression in parvo-, magno-cellular parts of the paraventricular nucleus and in the supraoptic nucleus in the course of behavioral depression development. Significant differences between control groups were seen only in paraventricular nucleus. On the 1st post-stress day in hypothalamus of KLA rats, we detected decreased CRH immune reactivity that remained unchanged up to the 10th day. In KHA rats, there were no notable changes of CRH expression in all studied nuclei. These findings, including previous results on different dynamics of behavioral changes and different hypothalamo-pituitary-adrenocortical system activity during development of depression in KLA and KHA rats, indicate that "learned helplessness" in these two groups of animals provides the model analogues of different types of depression. Besides, these findings indicate different implication of hypothalamus CRH-system in the behavioral depression development in rats with divergent strategy of adaptive behavior.     

The differences between sexes and strains in the capacity to acquire a passive avoidance conditioned reflex in KLA- and KHA-strain rats

The interstrain differences in passive avoidance conditioning were studied in male and female KHA (Koltushi High Avoidance) and KLA (Koltushi Low Avoidance) rats. These strains were selected for the rate of acquisition of active avoidance in a shuttle box. It was shown that the passive avoidance was substantially better acquired in the KLA strain than in the KHA. In females KHA rats the capability for passive avoidance conditioning depended on the estrus phase: the conditioning was impossible in proestrus.     

The role of corticotropin-releasing hormone in alteration of adaptive behavior of the active and passive rats after inescapable stress

Effects of corticotropin-releasing hormone (CRH) on the formation of post-stress psychopathology were studied using of two genetic strains KHA (Koltushi high Avoidance) and KLA (Koltushi low Avoidance) selected on high or low acquisition of active avoidance, respectively. These strains are characterized by higher (KHA) and lower (KLA) behavioral activity in open field and adopted, respectively, active and passive strategies in stressful conditions. A widely used experimental paradigm of learned helplessness where behavioral depression was produced by inescapable uncontrollable footshock has been applied in our study. KHA rats demonstrated psychopathology already 1st day following exsposure to the stress faktor, and the depression progressed by the 5th and 10th post-stress days. Intranasal application of CRH facilitated the development of depression in active rats. In KLA rats, which originally displayed low exploratory activity associated with high anxiety, the inescapable stress at first enhanced the exploratory behavior but 10 days later these rats displayed a progressive decline of exploration and locomotion. Initially, the application of CRH also enhanced the exploratory behavior in these rats, but to 10th post-stress day promoted development of depressive state. The results suggest that CRH in different ways affects the formation of depressive state in rats with different strategies of adaptive behavior.     

The effect of administering corticoliberin into the striatum on the open-field and shuttle-box behaviors of KHA and KLA strain rats]

The effects of corticotropin-releasing hormone (CRH) injected into the dorsal neostriatum on the open-field and shuttle-box behavior were studied in rats with high (Koltushi high avoidance, KHA) and low (Koltushi low avoidance, KLA) capability for avoidance learning. The effects of this hormone on the behavior of these rat strains were different. In KLA rats with passive strategy of behavior the CRH injection led to a rapid locomotor activation in the open field, while the rats with active behavioral strategy (KHA) reacted to the injection by a significant decrease in locomotion and change for the passive mode of behavior. The same CRH effects on locomotion were obtained in the shuttle-box experiments. Moreover, in the KLA rats the neurohormone injection resulted in an improvement of avoidance learning in contrast to the KHA rats, in which CRH substantially impaired avoidance learning. The obtained evidence is discussed in terms of the important role of striatal CRH in the choice of behavioral strategy in stress.     

Adaptive behavior of active and passive rats after intranasal administration of the corticotropin-releasing hormone

Behavioural effect of intranasal application of corticotropin-releasing hormone (CRH) was investigated in rats with high (KHA) and low (KLA) rate of learning in "open field" and plus-maze (PM) active avoidance test. The neurohormone provoked the opposed changes in behaviour of rats of this strain in both tests. The level of locomotion and exploratory activity rose in KLA rats and decreased in KHA rats. After the CRH application, the KLA rats but not KHA rats spent more time in the opened alleys of the PM than the control animals. The same behavioural changes were observed in our previous research when CRH was injected in striatum. We suppose that CRH is an endogenous factor of precise correction of the adaptive behaviour.     

Comparative analysis of the learning ability in Morris water test in rats with the various rate of active acquisition of the avoidance conditioned reflex

Place learning in Morris place navigation task was studied in male rats of KHA (Koltushi High Avoidance) and KLA (Koltushi Low Avoidance) rat strains. These strains were selected for different rate of acquisition of active avoidance in a shuttle box. At the initial stages of learning and after changing the experimental conditions, the performance of KLA rats was significantly better than that of KHA. Analysis of individual escape latency showed that the latency of the platform finding in the first trial had a significant effect on successful performance in the second trial. This effect was different in KHA and KLA rats. As distinct from KLA, the KHA rats demonstrated more rigid strategy in spatial orientation, the clear-cut thigmotropism was characteristic for their behavior in water.     

Intersex and interspecies differences in sucrose consumption by rats with various behavioral strategies]

Sucrose consumption by male and female rats during active avoidance acquisition was measured in two rat strains: KLA (Koltushi low avoidance) and KHA (Koltushi high avoidance) selected for divergent performance in a shuttlebox. Under resting condition, there were no interstrain difference in sucrose consumption by males, but KHA females consumed significantly less sucrose than KLA females. Active avoidance acquisition during five consecutive days decreased sucrose consumption in KLA males and did not change sucrose consumption in KHA males. Within a week after exposure to the stress, the sucrose consumption by KLA males returned to its normal values, and KHA males consumed significantly more sucrose. The active avoidance conditioning did not affect sucrose consumption in females of both strains. Substitution of 32% solution for 4% produced on the first day a sharp decrease in sucrose consumption in males of both strains, while females sharply increased consumption of the diluted solution over the next four days of observation. During this time, males returned to consumption of the same volume of the solution despite its decreased concentration. The findings suggest that the exposure to the escapable stress induces the negative affect only in KLA males.     

The extrahypothalamic level of the hypophyseal-adrenocortical system regulation appears to be involved in development of different types of depression-like state in rats

Possible role of extrahypothalamic corticotrophin-releasing hormone (CRH) and vasopressin-producing centers in post-stress depression development were studied. We used genetically selected strains: KHA (Koltushi High Avoidance) and KLA (Koltushi Low Avoidance) rats developing different types of depression in the "learned helplessness" paradigm: the model analogues of endogenous (KHA strain) and exogenous (KLA strain) depression. Interstrain differences of control and stress-induced CRH- and vasopressin-expression in hippocampus and neocortex in the course of depression development in KHA and KLA rats were revealed using immuno-histochemical studies. It has been shown that a significant increase of CRH- and vasopressin-immune reactivity in hippocampus and neocortex of KHA rats occurred on the 10th post-stress day. We detected also decreased CRH- and vasopressin-expression in dorsal hippocampus, and increased CRH-immune reactivity in neocortex of KLA rats in the same post-stress period. These findings imply that extrahypothalamic CRH- and vasopressin-ergic systems appear to be involved in pathogenesis mechanisms of model analogues of endogenous and exogenous depression in different ways.     

Dopaminergic processes in the striatum mediating corticoliberin effect on behavior of active and passive rats

The action of intranasal corticotropin-releasing hormone (CRH) administration on open field behavior and striatal and hypothalamic levels of dopamine, noradrenaline and their metabolites has been studied in rats with different behavior strategies (KHA and KLA strains). In KLA rats, CRH administration resulted in increased locomotor and exploratory activity, while KHA rats demonstrated decreased that. The analysis of catecholamine levels did not detect any strain differences in hypothalamus, but in striatum the dopamine levels have been twice higher, while the metabolite levels (DOPAC and HVA) were significantly lower in KLA rats as compared to KHA rats. The CRH administration led to increased dopamine and noradrenaline levels in hypothalamus and decreased those in striatum in rats of both strains, but in KLA the decrease was more evident. It is probably a result of intensified mediator turnover induced by the neurohormone in KLA rats, as supported by a fact of increased dopamine metabolite levels in this structure.     

Patterns of maternal behavior of rats genetically selected for opposite coping styles

Maternal behavior of Koltushi High- and Low-avoidance (KHA and KLA) rats strains was assessed over the prewealing period (days 6-21). Ten litters of each strain were observed during the light phase of the light/dark cycle. In a series of experiments, rat pups were taken from the maternal nest and placed into the opposite corner of the cage. The following parameters of the maternal behavior were recorded: the latency of the first contact with the pups, pup licking, latency of carrying/retrieval of the first pup back to the nest, time of returning to the nest of the whole litter, and mother's spontaneous behavior (grooming and locomotion time) over the course of 10 min of observation. KLA mothers stayed with their pups and took care of them more frequently than KHA mothers during the light phase of the circadian cycle. Time of self-grooming was significantly higher in KHA rats. The highest levels of self-grooming of mothers was registered on the first day of testing. The latency of the first coming to pups after their removal from the nest was lower in KHA rats, but they needed more time to returned all pups to the nest. The experimental evidence suggests that the KHA but not KLA rats with the active coping style and higher stress reactivity display disorders in maternal behavior in a novel situation.     

Dopaminergic mechanisms of the neostriatum in the corticoliberin regulation of adaptive behavior

Administration of corticotropin-releasing Hormone (CRH) to dorsal striatum in the course of active avoidance and open-field behaviour of genetically selected rats exerted different effects on adaptive behaviour of high-acquisition (KHA) and low-acquisition (KLA) rats. The findings suggest an important role of striatal dopamine in behavioural effect of the CRH.     

The behavioral characteristics of rats selected for their learning capacity]

Experiments were conducted in rat strains selected for high (KHA) and low (KLA) levels of the elaboration of conditioned reflex of active avoidance in shuttle box. KHA rats, as compared with the KLA ones, showed considerably higher indices of learning the shuttle avoidance, a greater number of intersignal runs during learning, a higher level of motor activity under open field conditions and its more marked extinction. These data point at the role of both associative and non-associative processes in the formation of active avoidance reflex. During 5 days of reflex training the rats of both strains retained a high level of defecation until the end of the test that pointed at the emotional strain unceasing in spite of the automatization of the reflex.     

Peroxidation of lipids in the brain of active and passive rats during development of poststress depressions

Peroxidation of lipids in a cortex of the large hemispheres, striatum, hippocampus and hypothalamus of rats of the lina KHA and KLA (Koltushi High and Low Avoidance) during development of poststress depressions was studied. After emotional painful act in initial terms of change, peroxidation of lipids had phasic character and differed in precise structural specificity. During maximal development of depression, the most expressed infringements of lipids peroxidation occurred in KHA rats in striatum and hippocampus, and at KLA rats--in the striatum and hypothalamus. The data confirm the important role of initial strategy of behavioral in mechanisms of pathogenesis of poststress psychopathology.     

Speed of exploration and risk-taking behavior are linked to corticosterone titres in zebra finches

The existence of consistent individual differences in behavioral strategies ("personalities" or coping styles) has been reported in several animal species. Recent work in great tits has shown that such traits are heritable and exhibit significant genetic variation. Free-living birds respond to environmental stresses by up-regulating corticosterone production. Behavior during mild stress can occur in accordance to two types of coping styles, i.e. active and passive. Using artificially selected lines of zebra finches that vary in the amount of corticosterone produced in response to a manual restraint stressor we ran three "personality" experiments. We show that birds in the different corticosterone lines differ in their exploratory and risk-taking behaviors. There was an increase in exploratory behavior as corticosterone titre increased but only in the low corticosterone line. Birds in high corticosterone line showed greater risk-taking behavior than birds in the other lines. Thus, in general, higher levels of circulating corticosterone following a mild stress result in greater exploratory behavior and greater risk taking. This study shows that lines of animals selected for endocrine hormonal responses differ in their "coping" styles or "personalities".     

Central histaminergic stimulation of pituitary--adrenocortical response in the rat

In conscious rats histamine, the H1-receptor agonist 2-pyridylethylamine (PEA), and the H2-receptor agonists dimaprit and impromidine given intracerebroventriculary (i.c.v.) increased the hypophyseal-adrenocortical response, evaluated indirectly through the corticosterone concentration in the blood serum. On a molar basis histamine was the most potent drug whereas its agonists were less potent in inducing an increased corticosterone response. Impromidine however, was far more active than dimaprit and PEA. The effect of histamine was significantly yet not totally antagonized by either mepyramine, a H1-receptor antagonist, or cimetidine, a H2-receptor blocker. The combination of mepyramine and cimetidine caused a considerably stronger inhibition than that induced by either antagonist given separately. Mepyramine impaired the corticosterone response to PEA, and the responses to impromidine and dimaprit were significantly diminished by cimetidine. The results suggest that i.c.v. histamine increases the pituitary-adrenocortical activity via both H1- and H2-receptors, and there seems to be no significant prevalence of either of these receptors in mediating this action of histamine.     

Effect of corticosterone on the prolactin response to psychological and physical stress in rats

Both corticosterone and prolactin (PRL) levels increase in response to stress. In these studies we examined the effect of corticosterone on the PRL response to both physical (footshock) and psychological (novel environment) stress. Three groups of rats were used: sham adrenalectomized (SHAM), adrenalectomized (ADX), and adrenalectomized with corticosterone replacement (ADX+CORT). The corticosterone-treated animals received 80 ug corticosterone/ml drinking water. Blood samples were drawn via an indwelling cannula and PRL values determined using radioimmunoassay. ADX rats showed a consistently greater PRL response to being placed on a platform above water (novel environment) or when receiving intermittant footshock than did ADX+CORT rats. The PRL response of the latter group was similar to that of the SHAM animals. These findings indicate that corticosterone levels of an animal can significantly attenuate the magnitude of the PRL response to both physical and psychological stress. These findings further emphasize that the PRL response to stress is dependent not only upon the immediate action of the stressor, but also the prior stress history of the animal.     

Rats with passive coping strategy have average,but not low social range

Social ranks were determined in rats with different degrees of activity-passivity in coping style. The dominance status of rats was assessed by their behavior during social interaction and during competition for food and water. Coping styles were determined during initial trials of acquisition of active avoidance in a two-way shuttle box. Animals with passive behavior in a shuttle box had average scores of social ranks. Both dominant and subordinate rats displayed significantly more active behavior than subdominant animals. In additional experiment, the rats were caged as a one male-one female pairs. Two weeks later, the social ranks of males were determined during agonistic interactions. Males were caged in triads, and corticosterone levels were assayed in blood samples taken from the tail veins during the first five days. The corticosterone level was significantly higher in subdominants than in dominants. There was no significant difference between the dominants and subordinates in corticosterone levels. The obtained evidence suggests the passive coping in subdominant rats, whereas the dominant and subordinate animals were more "active" under aversive stimulation.     

Central injection of morphine stimulates plasma corticosterone and interleukin (IL)-6 and IL-6 R mRNAs in the pituitary and adrenals in adjuvant-induced arthritis.

Adjuvant-induced arthritis (AA) in the rat is a T-cell mediated, chronic inflammatory stress in which circulating interleukin (IL)-6 levels are elevated. In addition, there are profound neuroendocrine changes associated with the development of hind-paw inflammation which have major implications for the ability of the rat to respond the to stress. Central injection of morphine is also able to increase circulating IL-6 concentration in control animals. In the present study we have determined the effects of a single injection of morphine into the lateral ventricle of control and AA animals on plasma corticosterone levels, on changes in plasma corticosterone and on IL-6 and IL-6 receptor mRNAs in the pituitary and adrenal gland. IL-6 and IL-6 receptor mRNAs were increased in the anterior pituitary of AA rats given moprhine compared with saline-treated AA rats. In the adrenal cortex, IL-6 mRNA was unaltered and IL-6 receptor mRNA was significantly decreased under these same conditions. AA rats were unable to mount corticosterone response to acute stress but were able to respond to acute stimulation with e.g. LPS. In the present study we found a sustained increase in plasma corticosterone in control animals which was still significantly elevated 2 hours following morphine injection, with a further significant increase in AA rats. These data suggest that alternative systems distinct from those activated in response to acute stress are activated by morphine in the AA animals. The similarity with the sustained increase in corticosterone following LPS injection suggest that either similar pathways are involved, or that central opiates may be involved in mediating HPA axis response to stress.