The neurobiology of the central nucleus of the amygdala in relation to neuroendocrine and autonomic outflow.
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Adaptation, Psychological↗
Biomedical subjects
J M Koolhaas
Publications and source records attributed to J M Koolhaas.
Forebrain pathways and their behavioural interactions with neuroendocrine and cardiovascular function in the rat.
1. The forebrain is a major organizer of the complex behavioural, physiological and neuroendocrine responses to environmental challenges of a stressful nature. 2. Combined physiological and neuroanatomical studies suggest that a specific forebrain-brain stem network, composed of connections between the central nucleus of the amygdala, the paraventricular nucleus of the hypothalamus, the mesencephalic cuneiform nucleus, the parabrachial nucleus and the dorsal motor nucleus of the vagus nerve, may be important for integrating behavioural and physiological responses. 3. Based on studies using bilateral electrolytic lesions of the central nucleus of the amygdala, it has become clear that the central nucleus of the amygdala is one of the key structures involved in unconditioned responses to inescapable footshock. These responses include freezing behaviour, tachycardia and the release of adrenaline, noradrenaline, prolactin and corticosterone. However, this nucleus is involved only in the freezing behaviour and bradycardiac responses to conditioned emotional stress or to social defeat. 4. Both peptidergic (corticotropin releasing hormone and vasopressin/oxytocin) and aminergic (noradrenaline and dopamine) mechanisms in the central amygdala are involved in the regulation of integrated behavioural, physiological and neuroendocrine stress responses. This is indicated by studies with an infusion of an agonist and/or antagonist of the peptides or neurotransmitters into the central amygdala of freely moving rats. Sympathetic cardiac control is intensified by corticotropin releasing hormone and oxytocin, probably by inhibiting vagal output. In contrast, vagal activity is facilitated by vasopressin, noradrenaline and dopamine.
Amygdala↗
A comparison between house mouse lines selected for attack latency or nest-building: evidence for a genetic basis of alternative behavioral strategies.
House mouse lines bidirectionally selected for either nest-building behavior or attack latency were tested for both attack latency and nest-building behavior under identical conditions. Male mice selected for high nest-building behavior had shorter attack latencies, i.e., were more aggressive, than those selected for low nest-building behavior and their randomly bred control lines. Conversely, male wild house mice selected for short attack latency showed more nest-building behavior than those selected for long attack latency when tested at 110 days of age. These findings imply a common genetic basis for control of aggression and nesting and support earlier proposals as to how animals may exhibit fundamentally different responses to environmental challenges, either reacting actively to aversive situations (aggressive and high-nesting animals: active copers) or adopting a passive strategy (nonaggressive and low-nesting animals: passive copers).
Aggression↗
Studies on wild house mice (VIII): Postnatal maternal influences on intermale aggression in reciprocal F1's.
Previous findings have shown a difference in attack latencies, i.e., aggression, between reciprocal F1's of a line selected for short attack latency (SAL) and a line selected for long attack latency (LAL). In the present study, we investigated the influence of postnatal maternal environment on attack latency scores (ALSs). The results show that only the evolution of the ALSs over 3 consecutive days is influenced by crossfostering. Accordingly, we conclude that the postnatal maternal environment affects ALSs only to a small extent.
Aggression↗
Individual characteristics of behavior, blood pressure, and adrenal hormones in colony rats.
Previous experiments suggested that rats with an active behavioral strategy and high endocrine and blood pressure responses to social interactions would be at risk to get a high blood pressure. To test this hypothesis, a long-term study of social behavior was performed in laboratory colonies of rats. The more aggressive rats, as indicated by individual precolony resident-intruder tests, are more aggressive in the colony also. After colony aggregation, the aggressive rats appeared to have higher resting blood pressures. The dominant rat (although aggressive, too) and the nonaggressive rats have lower blood pressures. Plasma levels of catecholamines and corticosterone after colony experience do not show a relation with blood pressure but reflect the rat's original precolony aggressive characteristic. We conclude that the individual characteristic of an active social strategy is a risk factor that indeed predicts the development of high blood pressure, possibly by way of the associated higher physiological reactivity we found earlier. Chronic environmental factors that are hard to control for the animal, like involvement in social processes or possibly other continuous challenges, may stimulate the prone physiology to develop an elevation of blood pressure.
Aggression↗
Behavioural activation produced by CRH but not alpha-helical CRH (CRH-receptor antagonist) when microinfused into the central nucleus of the amygdala under stress-free conditions.
The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine, and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH)-containing cell bodies and terminals. In the present study we examined (by continuous behaviour observations) the effects of a high dose of CRH (150 ng) and two doses of the CRH-receptor antagonist (alpha-hCRH: 1.0 and 0.1 micrograms) after microinfusion into the CeA in freely moving male Wistar rats under stress-free conditions. In comparison with control, alpha-hCRH infusion did not cause any behavioural activation. In contrast CRH-infusion revealed a long-lasting increase in grooming and exploration with a concomitant decrease in behaviours specified as resting. These results indicate that the CRH system in the CeA does not seem to be activated in stress-free conditions, but its activation is of importance for active behavioural responses.
Amygdala↗
Brain aromatase activity and plasma testosterone levels are elevated in aggressive male mice during early ontogeny.
Testosterone (T) and estradiol (E2) are involved in intraspecific aggressive behavior. Both steroids exert their effects on behaviour via the hypothalamus and the amygdala (Am) of the central nervous system (CNS). In these brain areas T is converted to E2, by the enzyme aromatase. Both the levels of brain aromatase activity (AA) and the effects of T and E2 on aggressive behavior in adulthood depend on steroidal organization of the CNS during ontogeny. In this study we measured plasma T and in vitro brain AA of males fetuses and neonates derived from two strains of wild house mice, which had been genetically selected for aggression, based upon attack latency. There were no differences in preoptic area (POA) AA levels between selection lines on either embryonic day (E) 17 or 18, or the day after birth (day 1). In the non-aggressive long attack latency (LAL) males the POA AA increases with age, i.e. was higher on E18 than on E17, which is correlated with brain weight (BrW). This was in contrast to aggressive short attack latency (SAL) fetuses, which only showed a slight, but not significant differences between embryonic days or a correlation with BrW. Neonatally, the POA AA of LAL males tended to decrease in contrast to SAL males. However, SAL neonates had a higher AA in the amygdala (Am) than LAL neonates, whereas no differences exist in the anterior hypothalamus. Thus, a differential brain AA distribution exists in SAL and LAL pups.(ABSTRACT TRUNCATED AT 250 WORDS)
Aggression↗
Aromatase activity in the preoptic area differs between aggressive and nonaggressive male house mice.
Treatment with testosterone (T) or estradiol (E2) facilitates intraspecific aggressive behavior in adult rodents. Brain aromatization of T to E2 appears to be involved in facilitation of fighting behavior. In the present study we measure the in vitro brain aromatase activity (AA) in the preoptic area (POA), amygdaloid nuclei (Am), ventromedial hypothalamus (VMH), and parietal cortex (CTX) from two strains of adult male house mice, which were genetically selected for territorial aggression, based upon their attack latencies (short attack latency: SAL; long attack latency: LAL). The results reveal a higher AA in the POA of nonaggressive LAL males, as compared to aggressive SAL animals. The POA AA is, thus, inversely correlated with aggressiveness. The AA levels in both the VMH and Am do not differ significantly between strains. Furthermore, a differential brain area-specific AA distribution exists: POA > VMH AA in LAL, whereas POA < VMH in SAL. In both selection lines, the Am exhibits the highest levels of AA, as compared to the other investigated areas. Kinetic studies revealed that the aromatase Km is similar in both strains. The results indicate that the strain difference in AA is specific to the POA, but is not necessarily positively correlated with circulating plasma T levels. Other factors, in addition to androgen, are probably involved in the regulation of POA aromatase. We suggest that a higher neural androgen receptor sensitivity exists in the POA of nonaggressive LAL males, resulting in higher adult POA AA, despite lower concentrations of circulating T.
Aggression↗
Strain specific behavioural response to environmental enrichment in the mouse.
The influence of environmental enrichment on the behaviour of the mouse has been studied in two inbred strains (C57BL and BALB/c). Male mice of each of the two strains were subjected to behavioural tests after being housed for two months either under standard housing conditions or in an enriched environment. The results of the behavioural test indicated that the C57BL mice housed in the enriched environment were more reactive and alert compared to mice housed in the standard environment. In the BALB/c mice results may be interpreted as if enriched environments lead to an increased level of anxiety. It is concluded that environmental enrichment has a strain specific effect on the behaviour of mice.
Animals↗
Corticotropin-releasing hormone microinfusion in the central amygdala diminishes a cardiac parasympathetic outflow under stress-free conditions.
The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies. Neuroanatomical studies revealed that the majority of the CRH fibres from the CeA have direct connections with autonomic regulatory nuclei in the brainstem. In the present study, the effects of locally infused CRH (30 ng) into the CeA, in freely moving male Wistar rats under stress-free conditions, were examined. Heart rate, endocrine parameters and behavioural activity were repeatedly measured before, during and after local administration of CRH, pretreated with either artificial CSF or the CRH-receptor antagonist, alpha-helical CRH (alpha-hCRH). CRH infusion alone caused a long-lasting increase in heart rate without affecting plasma adrenaline and noradrenaline as indicators of sympathetic activity. This CRH-induced tachycardia was effectively blocked by pretreatment with a high dose (1 microgram) alpha-hCRH locally into the CeA, while the pretreatment with low dose (0.1 microgram) of the alpha-hCRH caused a minor blockade of the CRH-induced tachycardia. The results suggest that CRH mechanisms in the CeA regulate the autonomic changes probably only by affecting parasympathetic but not sympathetic output systems. Because CRH is given at the level of the cell body of the CRH neurons in the CeA, we suggest that the reduction of the parasympathetic output may be explained as an autoreceptor-mediated inhibition of CRH neurons from the CeA with parasympathetic-regulating brainstem nuclei.
Amygdala↗
The neurohypophysial peptides, learning, and memory processing.
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Adrenal Medulla↗
A single social stress-experience alters glutamate receptor-binding in rat hippocampal CA3 area.
The distribution of glutamate receptors in the rat hippocampus was investigated 24 h after the social stress of confrontation with a dominant opponent. AMPA-type glutamate receptors were labeled with the antagonist [3H]CNQX, and NMDA-type receptors were labeled with the competitive antagonist [3H]CGP39653. Increased [3H]CGP39653 labeling was exclusively found in the CA3 stratum radiatum and a decreased [3H]CNQX labeling was found in several hippocampal areas. Consequently, the ratio NMDA/AMPA binding was significantly increased in CA3 stratum oriens and CA3 stratum radiatum. These results suggest that a single unescapable social stress of defeat alters the impact of the excitatory neurotransmitter glutamate, which is restricted to hippocampal CA3 neurons. Possible consequences of the present findings are discussed.
2-Amino-5-phosphonovalerate↗
Differential perinatal testosterone secretory capacity of wild house mice testes is related to aggressiveness in adulthood.
Testosterone secretory capacity of testicular Leydig cells was determined in fetal males of an aggressive and a nonaggressive genetic selection line of wild house mice. They were studied at Days 15-18 of gestation and on the first day after birth. A previously described morphometric method was used to quantify 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD)-stained Leydig cells in testicular sections to determine testosterone secretory capacity, which may be considered to reflect circulating plasma testosterone in the fetus. The results of this study show that the testosterone secretory capacity of Leydig cells in the testis changes differentially during intrauterine development in males of the aggressive and nonaggressive selection lines. The peak secretory capacity is reached at Day 17 of gestation for the males of the aggressive selection line, while the peak for the nonaggressive males is reached on the first neonatal day. The larger anogenital distance observed in aggressive males suggests a higher prenatal testosterone level in these males. The importance of the difference in timing of the perinatal 3 beta-HSD peak top individual variation in adult aggressive behavior is discussed.
3-Hydroxysteroid Dehydrogenases↗
Relationship between feeding, stereotypies, and plasma glucose concentrations in food-restricted and restrained sows.
Previous work has shown that stereotypies, such as chain manipulation and excessive drinking, only develop in food-restricted sows. Furthermore, once stereotypies have been developed, ingestion of a small meal specifically stimulates the performance of stereotypes. These results suggest that the occurrence of stereotypies may strongly depend on the individual's nutritional status. As glucose is one of the main metabolic fuels, the present experiment investigated whether individual differences and/or daily variations in levels of chain manipulation and excessive drinking are correlated to individual differences and/or daily variations in pre- or postfeeding glucose concentrations. Blood samples were taken at regular intervals prior to, during, and after feeding, from sows that had developed stereotypies to different degrees over a period of 110 days of restrictive housing and feeding conditions. Glucose concentrations were low prior to and high after feeding. Levels of stereotypies showed similar variations, suggesting that the performance of stereotypies is not related to low glucose concentrations. Furthermore, whilst sows differed consistently in glucose concentrations, no correlations were found between individual glucose concentrations and stereotypies. Similarly, no correlations were found between glucose concentrations and chain manipulation or drinking on a sample to sample basis. These data show that although performance of stereotypies is strongly dependent on feeding regime, it is not related to plasma glucose concentrations.
Animals↗
Genetic differences in female house mice in aggressive response to sex steroid hormone treatment.
Male mice, genetically selected for aggression, characterized by short attack latency (SAL) or long attack latency (LAL), differ on several testosterone (T)-related parameters during ontogeny and adult age. The variation in aggressive behavior at adult age may be due to differences in degree of androgenization prenatally. When exposed to T at prenatal, neonatal, and/or adult age, nonlactating females also display intraspecific fighting behavior. In the present study, we investigated in females of the SAL and LAL selection lines, whether the differentiation of aggression involves processes similar to ones seen in males. Therefore, we injected females with testosterone propionate (TP) or vehicle on the day of birth, treated them after ovariectomy at adult age with T, estradiol (E), or vehicle, and tested their aggressive response. We found that neonatally vehicle-treated SAL females show a higher aggressive response to chronic T treatment at adult age than LAL females receiving the same treatment. Females of both selection lines treated with vehicle or E as adults were not aggressive. Neonatal TP treatment did not influence the adult T sensitivity and difference between selection lines in response to T at adult age. However, neonatally TP-treated SAL females showed aggressive behavior when treated with E at adult age, whereas LAL females failed to do so. These results suggest a genetic difference in susceptibility to T and E, which plays a major role prenatally, in organizing the development of sex steroid-dependent neural systems.
Aggression↗
Neuroendocrine and behavioral effects of vasopressin in resting and mild stress conditions.
Neuroendocrine and behavioral effects of subcutaneously administered AVP (6 micrograms/kg b.wt.) were determined in resting conditions and after the mild stress of transportation to and placement in a novel environment. In resting conditions, systemic administration of AVP caused a rapid increase in blood glucose level and a long-lasting increase in CORT secretion. A decrease in circulating plasma NE level was observed. AVP did not affect adrenal medullary E secretion. The stress-induced sympathetic activation, as reflected in plasma NE level, was inhibited 60 min after AVP administration. Stress-induced increases in blood glucose, CORT, and E secretion were not influenced by AVP. In resting condition, AVP caused a 60-min lasting increase in grooming behavior with a concomitant decrease in time spent resting. Sixty minutes after administration, the behavioral activation after the stress of transportation and placement in a novel environment was more rapidly terminated in AVP-treated rats than in vehicle-treated control rats. The state- and time-dependent modulation of spontaneous behavior suggests that AVP has arousing properties shortly after administration when marked pressor and endocrine effects are apparent. In a later phase, AVP may facilitate dearousal mechanisms following stress-induced behavioral activation.
Animals↗
The central amygdala is involved in conditioning but not in retention of active and passive shock avoidance in male rats.
The present study was designed to further characterize the involvement of the central amygdaloid nucleus (CEA) in the conditioning and the retention of both active and passive stress-related behaviors. Active shock avoidance was investigated in a shuttle-box. CEA-lesioned and sham-operated animals received 30 trials on 2 consecutive days. During the first day of conditioning, the CEA-lesioned animals failed to learn to avoid, but on the second day these rats showed avoidance behavior that was comparable to the sham-lesioned ones. When lesioned animals received a total of 60 trials on 1 day, they failed to show avoidance, suggesting deficits in acquisition performance but presence of latent learning following CEA lesioning. However, the retention response, which was studied by lesioning the CEA between a 2-day avoidance training and a retention test, was unaffected. Stress-related learning was also studied in a test of passive avoidance of a previously received single, inescapable electric footshock. When the lesion was placed before the single learning trial, the retention of the response was absent. However, CEA-lesioning after the learning trial revealed no differences between the CEA-lesioned and sham-lesioned animals. In conclusion, these results demonstrate that the CEA is involved in the conditioning rather than retention of both active and passive shock avoidance responses.
Amygdala↗
Differential lateral septal vasopressin innervation in aggressive and nonaggressive male mice.
The vasopressinergic (VP) projection from the bed nucleus of the stria terminalis (BNST) to the lateral septum (LS) is sexually dimorphic and dependent of androgens at adult and neonatal age. We studied the relation between testosterone (T) and VP in male mice, which were genetically selected for their differences in aggression level. Aggressive males, characterized by a short attack latency (SAL), have a higher production capacity of T at adult age compared to males with a long attack latency (LAL). Neonatally, however, a higher T production occurs in the nonaggressive LAL males than in SAL males. In the present study we showed a more dense VP-immunoreactive (VP-ir) innervation in the LS and a higher VP-ir neuron density in the BNST of LAL males as compared to SAL males. The described differences may be the consequence of a differential neonatal androgen effect on the organization of the forebrain vasopressinergic network.
Aggression↗