W. Meelis

Fast positive feedback between the adrenocortical stress response and a brain mechanism involved in aggressive behavior.

Aggressive behavior induces an adrenocortical stress response, and sudden stressors often precipitate violent behavior. Experiments in rats revealed a fast, mutual, positive feedback between the adrenocortical stress response and a brain mechanism controlling aggression. Stimulation of the aggressive area in the hypothalamus rapidly activated the adrenocortical response, even in the absence of an opponent and fighting. Hypothalamic aggression, in turn, was rapidly facilitated by a corticosterone injection in rats in which the natural adrenocortical stress response was prevented by adrenalectomy. The rapidity of both effects points to a fast, mutual, positive feedback of the controlling mechanisms within the time frame of a single conflict. Such a mutual facilitation may contribute to the precipitation and escalation of violent behavior under stressful conditions.

Effect of environmental stressors on time course, variability and form of self-grooming in the rat: Handling, social contact, defeat, novelty, restraint and fur moistening

Grooming is often related to dearousal following stressors. Interestingly, electrical and chemical stimulation of the paraventricular nucleus of the hypothalamus (PVH), at levels that are known to activate the hypothalamus-pituitary adrenal axis (HPA), also elicits grooming. At the level of the PVH, the neuroendocrine stress response is apparently still linked to the behavioural response to stressors. However the precise nature of this relation is not fully understood. Here we report on grooming in rats following exposure to different stressors which are known to activate the HPA axis. Stressors such as handling, restraint, novelty, encounters with aggressive or non-aggressive conspecifics, or moistening the fur, change the amount and time course of grooming upon return in the home cage, as compared with controls that are just handled. However, the amount of grooming is not directly related to the strength of the stressor. Defeated intruders groom less upon return in their home cage. Novelty and non-aggressive encounters with conspecifics reduce the variation in the amount of grooming between rats. The time course of grooming over the 20-min observation period also differs between treatments. Following restraint, or exposure to non-aggressive conspecifics, grooming first increases and then decreases. Moistened rats immediately start grooming which subsequently decreases. Rats used as intruders in the territory of another rat maintain a constant low level of grooming. Rats placed in a novel cage steadily increase grooming during the 20-min observation period. These results suggest that grooming cannot be simply understood as an immediate response necessary to reduce arousal following stressors. Following exposure to a stressor, grooming rather seems temporary suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic substrates for brain stimulation-induced attack, teeth-chattering and social grooming in the rat.

In this paper the boundaries of the hypothalamic response areas for brain stimulation-induced attack, social grooming and teeth-chattering were delimited. A total of 641 hypothalamic sites in 71 male CPW/WU Wistar rats were electrically stimulated. Positive sites for any behavioural response cluster into restricted hypothalamic areas. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate and low probabilities of inducing the behavioural response concerned. Each response has its own response area where probabilities are high. Neuroanatomical correlates of these response areas are discussed. The response area of attack is suggested to be an integrative processing area, stimulation of which overrules some aspects of integration and directly activates the behavioural program of attack. Although some authors consider all three responses to be part of the behavioural repertoire of aggression, the response areas are not identical. Social grooming and attack are considered to be induced from different neural systems. Similarly, attack and teeth-chattering have been shown to derive from different neural mechanisms, despite substantial overlap of both response areas. It is suggested that teeth-chattering derives from the simultaneous activation of both attack and flight tendencies. No further distinctions with respect to threshold current intensities can be made within responses areas. However, the underlying neural substrates are not homogeneous, for thresholds vary along the course of individual electrodes.

Hypothalamic substrates for brain stimulation-induced patterns of locomotion and escape jumps in the rat

The hypothalamic response area for electrically induced locomotion was determined using moveable electrodes and discriminant analysis as an appropriate statistical technique. At 241 out of 641 stimulated sites locomotion was induced. The distribution of locomotion sites is relatively diffuse. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probability of inducing the response. The response is considered to be mediated by fibres of the subpallido-pedunculopontine system, which includes the mesencephalic locomotor region. Different categories of exploratory and flight-directed locomotion were distinguished, and response areas for both categories were determined. In addition the response area for escape jumps was delimited. Exploratory locomotion is mainly induced from the lateral hypothalamus, while flight-directed locomotion and escape jumps are evoked from the medial hypothalamus. The response area for exploratory locomotion reflects the lateral hypothalamic distribution of the subpallidal projection to the mesencephalic locomotor region. A diffuse substrate for flight behavior seems to occupy almost the entire medial hypothalamus. It is concluded that a locomotor subroutine subserving different behavioural mechanisms can be activated at many hypothalamic sites.

Comparison of Aggressive Behaviour Induced by Electrical Stimulation in the Hypothalamus of Male and Female Rats

Publisher Summary Sex differences in aggressive behavior are present in many species, and the genders often become aggressive in different ways or in different conditions. This chapter describes and attempts to induce aggression by stimulation in the hypothalamus of female as well as male rats and compares behavior, histology, and current intensity required to induce attacks in the two sexes. The chapter also discusses the effects of ovariectomy and subsequent oestradiol replacement on attack thresholds in female rats. The results show that electrical stimulation in the hypothalamus elicits aggression in both male and female rats, which seems to be derived from the same neural systems and no sex differences could be detected in the sensitivity of these neural systems to stimulation. Slight differences are observed in the forms of attack behavior induced by hypothalamic stimulation: males tend to show more intense, females weaker forms of attack. These differences may be due to hormonal differences of the animals, the males having normal levels of testosterone. Neither ovariectomy nor subsequent oestrogen replacement affects thresholds for hypothalamic attack in a convincing way, which is in contrast with the effects of castration and testosterone replacement in male rats. However, the precise neural mechanisms of this behavioral facilitation are not known.

Hypothalamic attack area-mediated activation of the forebrain in aggression

It is believed that aggressive attacks are activated by a downward stimulatory stream that includes the medial amygdala, hypothalamic attack area, and periaqueductal grey. However, the hypothalamic attack area (from which attacks can be induced by electrical stimulation) sends projections to the forebrain, the significance of which is unknown. Here we report that the unilateral stimulation of the hypothalamic attack area per se induced an unilateral c-Fos activation of most brain nuclei involved in attack, and that attacks occurred only when cortical regions were also activated, and the activation of the medial amygdala and hypothalamic attack area were bilateral. This suggests that the hypothalamic attack area not only transmits information to lower brain structures but also activates forebrain structures involved in attack.

Hypothalamic substrates for brain stimulation-induced grooming, digging and circling in the rat

Despite a great number of studies concerned with the induction of specific behavioural responses from the rat hypothalamus by electrical brain stimulation, hypothalamic response areas and underlying neural substrates have never been determined accurately. In this study the boundaries of the hypothalamic response areas for grooming, digging and circling were delimited using moveable electrodes, an enriched environment containing a variety of goal objects, and an appropriate statistical technique. A total of 641 hypothalamic sites in 71 male CPB/WU Wistar rats were electrically stimulated. Results are plotted on a detailed stereotaxic brain atlas of the rat hypothalamus. Positive sites for any behavioural response cluster into restricted hypothalamic areas. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probabilities of inducing the behavioural response concerned. Each response has its own response area where probabilities are high, although there may be overlap. Even within response areas a distinction can be made between areas in which the response can be induced at relatively high or low threshold current intensities. Lowest threshold sites within electrode tracks are often clustered. In search of neuroanatomical correlates, grooming is related to the distribution of ACTH-immunoreactive neural elements, digging is related to the distribution of efferent fibres from the bed nucleus of the stria terminalis, and circling is related to the distribution of dopaminergic fibres of the nigrostriatal pathway. The results clearly point to the stimulation site being the most important determinant of the evoked behavioural response. Evidently behavioural specificity does exist within the hypothalamus.

Aggressive behavior induced by electrical stimulation in the midbrain central gray of male rats

Electrical stimulation via electrodes implanted in the lateral hypothalamus may induce intraspecific aggressive behavior. Small electrolytic lesions placed via these electrodes resulted in a five– to tenfold increase in the current threshold for aggression. Degenerating fibers were stained by means of the Fink-Heimer method and could be followed caudally to the dorsal midbrain central gray and to the mammillary bodies. A few axons could be traced rostrally to the medial septum. Aggression could be induced from 10 of 112 electrodes implanted in the central gray; the other electrodes elicited either locomotion, vocalization, jump, or “alarm-like reactions.” The morphology of the induced aggression was similar to the morphology of the hypothalamically induced aggression, though it was often accompanied with motor disturbances and was less intense. Hypothalamic stimulation was combined with simultaneous central gray stimulation in rats with electrodes both in the hypothalamus and in the central gray. Hypothalamic thresholds for aggression could be lowered by this stimulation of the central gray, even when no aggressive responses were observed during central gray stimulation alone. This suggests that, although aggression is not manifest, electrical stimulation may activate neural tissue involved in aggressive behavior. It is concluded that in rats central gray and hypothalamus are part of the same neural network mediating intraspecific aggression.

Behavioural effects of NMDA injected into the hypothalamic paraventricular nucleus of the rat.

Electrical stimulation of the hypothalamic paraventricular nucleus (PVH) and of the adjacent dorsal hypothalamic area (DHA) evokes grooming behaviour. Microinjections of low doses of kainic acid, an agonist of the kainate type of glutamate receptors, into the same area evokes the same behaviour. To test whether other glutamate receptors are involved, microinjections with N-methyl-D-aspartic acid (NMDA) were made into the PVH/DHA area and the behaviour was observed. From the total observation time (30 min) up to 73% was spent on grooming, accompanied by yawning. Pronounced feeding behaviour was also noticed at 3 injection sites but not until 23 min after injection. Conclusions are that neurones within the PVH/DHA area are involved in grooming behaviour, possibly via glutamatergic innervation. The interaction between grooming and feeding behaviour at the level of the PVH is discussed.

Anti-aggressive effect of a new phenylpiperazine compound (DU27716) on hypothalamically induced behavioural activities

Using the same hypothalamic electrodes, the following behaviour was evoked in male rats by electrical stimulation at roughly equal current intensities: attacks on a partner, teeth-chattering, switch-off behaviour and locomotion. Current thresholds were determined for each behaviour following the intraperitoneal administration of saline or DU27716, a new phenylpiperazine compound with interesting inhibitory effects on territorial and intermale aggression. DU27716 raised current thresholds for attack and teeth-chattering beginning at the lowest dose (4 mg/kg), whereas there was no effect on switch-off behaviour, and only a slight but significant effect on locomotion thresholds at the highest dose (8 mg/kg). The results provide support for the hypothesis that DU27716 possesses behaviourally selective, anti-aggressive properties, and illustrate the usefulness of hypothalamically induced behaviours as a pharmacological model.