Effects of midbrain central gray lesions on spontaneous and electrically induced aggression in the rat

Large electrolytic lesions were placed in the midbrain central gray of male rats. Their effects on hypothalamically induced aggression, switch-off behaviour, and locomotion were investigated. A number of these animals were also tested for territorial intermale aggression in order to compare electrically induced and spontaneous aggression. Large lesions resulted in an increase of the current threshold to induce aggression by hypo-thalamic stimulation. Smaller, but still quite large, lesions decreased the threshold current for hypothalamic aggression. After the operation a decrease in the threshold for switch-off was present, both in the experimental and the control group. Current thresholds for locomotion were decreased after the lesions only in the experimental group. Spontaneous aggression was temporarily decreased after the lesion. No indication was found that other behavioural elements of the animal were distorted by the lesion. The parallel between the effects on spontaneous and electrically induced aggression makes it attractive to ascribe a role to the neural circuit of hypothalamus and central gray in territorial aggression. However, even with large lesions the animals were still capable of fighting, hence the central gray is not indispensable. An attempt was made to explain the differential effects that differently sized central gray lesions have on hypothalamic aggression.     

Midbrain-hypothalamic interrelationships in the control of aggressive behavior

Previous studies have suggested an involvement of the midbrain ventral tegmental area in the biting attack upon a rat elicited by electrical stimulation of the lateral hypothalamus in cats. In order assess further the relationship between these two regions, 12 cats were implanted with attack-eliciting electrodes in both the lateral hypothalamus and the midbrain ventral tegmental area. Following a lesion of the midbrain attack site, attack previously elicited from hypothalamic electrodes ipsilateral to the lesion was eliminated or significantly reduced in frequency. The attack elicited from electrodes in the hypothalamus contralateral to the lesion was unaffected. Midbrain lesions made at sites from which attack was never elicited had no effect on hypothalamically elicited attack. The midbrain lesion in some cases eliminated only certain components of the total attack pattern; for example, the approach of a cat to the rat frequently remained present while the bite was absent. Additionally, it was found that the attack elicited from rostral hypothalamic electrodes was disrupted to a greater degree by a single midbrain lesion than the attack elicited from more caudal hypothalamic electrodes. These finding are discussed in terms of the neural system mediating this form of aggressive behavior in cats.     

Androgens and aggressive behavior in primates: A review

This review deals with possible central and peripheral effects of androgens upon primate aggressive behavior. One problem that clouds interpretation of experimental work is that measurements of dominance have often been employed, such as competition tests for food and water. Such measures often do not correlate with those obtained by quantifying aggressive interactions. It should be remembered that very few of the 188 primate species have been studied experimentally and that great behavioral and physiological diversity occurs within the order. Therefore, generalizations about the effects of androgens upon aggressive behavior in primates (including man) should be made with caution. Testosterone has an organizing influence upon the foetal brain of rhesus monkeys and may affect the development of neural mechanisms which govern aggression in males. More data are required on primates, however, since rhesus monkeys show some important differences from rodents as regards the effects of androgen upon sexual differentiation of the hypothalamus. In future, marmosets may provide a suitable model for such studies, because there is evidence that sexual differentiation of brain by androgen occurs postnatally in these monkeys. At puberty, male primates show a variety of behavioral changes and, during adulthood, males of seasonally breeding species may be more aggressive during the mating season, when testosterone levels are maximal. This does not indicate a causative relationship between testosterone and aggressive responses, because castration and androgen treatments have little effect upon aggression in prepubertal or adult males of several primate species. Androgens have pronounced effects on sexual responses in adult male monkeys, but their central effects upon aggression are much less important than among rodents. Elec trical stimulation of hypothalamic pathways has been employed to evoke aggressive behavior in marmosets and rhesus monkeys. In the rhesus, preliminary evidence indicates that such pathways show some sensitivity to androgens. In rodents it is known that these areas are richly supplied with monoaminergic neurons, which play an important role in aggressive behavior. There is little evidence on primates, however, and this remains a crucial topic for future research. Peripheral effects of androgens should also be considered. Many prosimians and New World monkeys use scent-marking behaviors and, in males, androgen-dependent chemical cues may be involved in sexual recognition and territorial behavior. This possibility awaits investigation. Finally, plasma testosterone levels may alter as a function of aggression itself; thus levels decrease if male rhesus monkeys are defeated by conspecifics. This might occur because neural events associated with giving (or receiving) aggression also influence pituitary function and hence alter gonadal testosterone secretion. Theoretically, it is possible that such changes in circulating testosterone might affect aggressive behavior via a feedback action on the brain, but the experimental evidence does not support such a view.     

Aggressive behavior inhibition by serotonin and quipazine injected into the amygdala in the rat

The effects on aggressive behavior, open-field activity, and pain threshold of bilateral microinjections of serotonin (20 micrograms) and quipazine (20 micrograms), the direct serotonergic receptor agonist, into the cortico-medial amygdala were investigated in Wistar rats. Both drugs significantly prolonged the attack latency in isolated killer rats (predatory aggression model), and suppressed the incidence of aggressive postures/attacks in shock-induced fighting test (affective aggression). The only difference in the open-field behavior was the lower number of central square entries in drug-treated compared to saline-injected rats. None of the substances produced any significant change in jump threshold. It is concluded that stimulation of serotonin receptors within the amygdala produces inhibition of affective and muricidal behavior in isolated rats. The effect does not seem to be dependent on changes in general activity and pain sensitivity.     

Control of-treadmill exercise of rats with hypothalamic stimulation

Running and resting behavior of rats was measured during treadmill exercise under conditions involving (1) rear-shock avoidance, (2) continuous electrical stimulation of the hypothalamus, or (3) no rear-shock and no hypothalamic stimulation. Hypothalamic stimulation was superior for eliciting consistent running with a minimum of resting. A second experiment demonstrated that decreases in hypothalamically elicited treadmill running resulting from prolonged exercise could be counteracted by increasing the intensity of the hypothalamic stimulus. A third experiment suggested that very little training was needed to induce a high and consistent level of running performance using hypothalamic stimulation.     

The neural pathways mediating quiet-biting attack behavior from the hypothalamus in the cat: A functional autoradiographic study

Electrical stimulation of the region of the lateral hypothalamus produced a consistent form of quiet-biting attack behavior in cats. In one series of experiments, cats, implanted with electrodes from which attack had been elicited, were anesthetized and then were injected with a bolus of ¹⁴C-2-deoxyglucose at the same time as electrical stimulation was delivered through the attack electrodes. Brains prepared for X-ray autoradiography revealed that lateral hypothalamic stimulation activated the classical medial forebrain bundle pathway supplying the septal region, diagonal band, lateral preoptic area, and ventral tegmental region. Stimulation of quiet-attack sites in perifornical hypothalamus resulted in the activation of a much more extensive projection system which included the central and lateral tegmental fields of the midbrain and pons, and central gray region, as well as the structures described above. In a second series of experiments, ³H-leucine was placed into the region of the electrode tip from which attack was elicited in order to identify more precisely the pathways arising from that site. In general, tritiated amino acid radioautography replicated the ¹⁴C-2-deoxyglucose findings. In addition, the amino acid radioautographic data revealed the presence of extensive projections from perifornical hypothalamus to such pontine structures as the nucleus locus coeruleus, motor nucleus of NV , and the lateral pontine tegmental field. The functional connections between the lateral hypothalamic “attack region” and lateral preoptic zone were also confirmed by electrophysiological methods.     

Directional interaction of midbrain and hypothalamus in the control of carbachol-induced aggression

Microinjection of carbachol into the ventromedial part of the anterior hypothalamus or the ventrolateral part of the mesencephalic central gray elicits affective aggression in the cat. Pretreatment with atropine in the same site blocks carbachol-induced aggression. Prior administration of atropine into the midbrain blocks aggression induced by carbachol injections into the hypothalamus, but atropine injected into the hypothalamus does not prevent affective aggression elicited by carbachol administered into the midbrain. The results demonstrate a directional interaction between midbrain and hypothalamus, and provide suggestive evidence for a hierarchal organization of these limbic structures in the control of cholinergically-mediated affective aggression.     

Conditioned and unconditioned fear organized in the periaqueductal gray are differentially sensitive to injections of muscimol into amygdaloid nuclei

The lateral and basolateral nuclei of the amygdala (LaA and BLA, respectively) serve as a filter for unconditioned and conditioned aversive information that ascends to higher structures from the brainstem, whereas the central nucleus of the amygdala (CeA) is considered to be the main output for the defense reaction. It has been shown that the dorsal periaqueductal gray (dPAG) is activated by threatening stimuli and has important functional links with the amygdala through two-way anatomical connections. In this work, we examined the influence of chemical inactivation of these nuclei of amygdala on the freezing and escape responses induced by electrical stimulation through electrodes implanted in the dPAG of Wistar rats. Each rat also bore a cannula implanted in the LaA, BLA or CeA for injections of muscimol (0.5 microg/0.5 microL) or its vehicle. The duration of freezing behavior that outlasts electrical stimulation of the dPAG was also measured. On the following day, these animals were submitted to a contextual fear-conditioning using foot shocks as unconditioned stimulus. Conditioned freezing to contextual cues previously associated with foot shocks was also inhibited by injections of muscimol into these amygdaloid nuclei. The contextual conditioned freezing behavior is generated in the neural circuits of conditioned fear in the amygdala. The data obtained also show that injections of muscimol into the three amygdaloid nuclei did not change the aversive threshold of freezing, but disrupted the dPAG post-stimulation freezing. Previous findings that the latter freezing results directly from dPAG stimulation and that it is not sensitive to a context shift suggest that it is unconditioned in nature. Thus, the amygdala can affect some, but not all, aspects of unconditioned freezing. Post-stimulation freezing may reflect the process of transferring aversive information from dPAG to higher brain structures.     

Spontaneously hypertensive Wistar-derived male rats are more aggressive than those of their normotensive progenitor strain

We compared a group of spontaneously hypertensive rats (SHRs) to a group of Wistar-Kyoto (WKY) rats on each of the three most commonly studied forms of aggressive behavior in rats: muricide, intraspecific aggression, and shock-induced fighting (SIF). A significantly higher proportion of SHRs were muricidal; they also fought more at the lowest shock level. A trend for a higher incidence of intraspecific offense behaviors by SHRs was not significant. SHR flinch and jump thresholds were lower than the respective WKY thresholds. Although there were no significant correlations between shock thresholds and any aspects of SIF, the possibility that strain differences in shock sensitivity may contribute to differences in SIF cannot be ruled out. Within strains, there were no correlations among the different forms of aggression. Several different inherited characteristics may be associated with the accentuation of different forms of aggression in SHRs.     

Cross-tolerance between two brainstem sites supporting stimulation-produced analgesia

Male albino Holtzman rats were stereotaxically implanted with two bipolar stimulating electrodes, aimed at the periaqueductal gray matter of the brainstem. Focal brain stimulation-produced analgesia was assessed by the tail-flick method. After establishing that focal brain stimulation elicited analgesia at both sites, behavioral tolerance (i.e., reduced analgesia) was induced at one site through repeated stimulation. Upon elicitation of tolerance at one site, stimulation was immediately switched to the other site (which had not been previously rendered tolerant) and analgesia was assessed. Tail-flick latencies revealed transfer of behavioral tolerance from the site given repeated stimulation to the site not given repeated stimulation. While the mechanism involved in this cross-tolerance is not known, a neurochemical substrate may be involved.     

Predatory aggression: Midbrain-pontine junction rather than hypothalamus as the critical structure?

Electrical stimulation of sites in the region of the ventromedial periaqueductal gray substance at the level of the midbrain–pontine junction was found to elicit a predatory attack by a cat upon a rat. The intensity of stimulation required to elicit the attack was three to four times less than that required to elicit similar behavior by hypothalamic stimulation. The results suggest that anatomically distinct regions of the periaqueductal gray substance are concerned with the regulation of predatory and affective forms of aggressive behavior. The difficulty in reconciling these results with the preeminent role assigned the hypothalamus in the organization of predatory behavior is also discussed.     

Intra-female aggression in the mouse (Mus musculus domesticus) is linked to the estrous cycle regularity but not to ovulation

Intraspecific communication between mice takes place mainly via urinary chemosignals or "pheromones". Pheromones can influence aggressive and reproductive behavior as well as the neuroendocrine condition of the recipient female mice via their olfactory system. In this study, reproductively cyclic mice in the estrus phase were used to test intraspecific agonistic aggressive behavior. Data were obtained also on the count of the eggs shed in the oviducts. The results showed that (i) individually housed female mice are more aggressive toward an intruder female mouse than grouped mice, (ii) mice in which the vomeronasal organ was removed show aggressive behavior intermediate between individually housed and grouped mice, and (iii) a within group analysis did not show a positive correlation between aggression and presence of shed eggs in the oviducts.     

The ventromedial hypothalamus and aggressive behaviour in rats

Male rats were given bilateral lesions in either the anterior or posterior ventromedial hypothalamus (VMH). The intermale aggressive behaviour of these animals within their own territory was observed before and after the surgical procedure and compared with the behaviour of sham-operated animals. The effects of anterior VMH lesions include an increased tendency to respond with frontal threatening upon approach of a conspecific male. This behaviour closely resembles the aggressive responses described in “shock-induced aggression” tests. Posterior VMH lesions facilitate territorial aggressive behaviour characterized by approaching the opponent followed by lateral threatening and fighting. It is suggested that 2 distinct neural substrates exist, which serve to inhibit defensive (anterior-VMH) and offensive (posterior-VMH) intermale aggression, respectively.     

Centrally elicited aggressive behavior: A model system for the study of episodic neurobehavioral pathologies?

Studies in which the predatory-like attack of a cat upon a rat has been elicited by electrical brain stimulation have been briefly reviewed with an emphasis on the question of where within the central nervous system such brain stimulation is producing its behaviorally meaningful effects. Two opposing but by no means mutually exclusive views are considered. The first is that brain stimulation elicits this behavior pattern primarily because it affects a specific motivated behavior system that is organized discretely in the midbrain and pons. The second is that forebrain neural activity is modulated in behaviorally significant ways by brainstem stimulation, which elicits predatory-like aggressive behavior in the cat. The possibility that further research on the altered state of central nervous system activity, induced by brain stimulation which elicits aggressive behavior in the cat, may lead to a further understanding of the altered states of central nervous system activity that underlie the aggressive dyscontrol syndrome and other episodic state disorders is discussed.     

Escalation of irritable aggression: Control by consequences and antecedents

Two experiments demonstrated that rats could be trained in a negative reinforcement paradigm to display a shock-induced aggressive response on the first shock presented. Later, rats that had been submitted to the negative reinforcement training procedure displayed more shock-induced aggression than did control groups during a test session that was situationally different from the one used during training. A third experiment demonstrated that noxious antecedent events, if presented with sufficient rapidity, can combine to increase the probability of aggressive behavior. The three experiments together suggest that aversive antecedents and reinforcement contingencies could be involved in the escalation of irritable aggression.     

Lesion of the ventral periaqueductal gray reduces conditioned fear but does not change freezing induced by stimulation of the dorsal periaqueductal gray

Previously-reported evidence showed that freezing to a context previously associated with footshock is impaired by lesion of the ventral periaqueductal gray (vPAG). It has also been shown that stepwise increase in the intensity of the electrical stimulation of the dorsal periaqueductal gray (dPAG) produces alertness, then freezing, and finally escape. These aversive responses are mimicked by microinjections of GABA receptor antagonists, such as bicuculline, or blockers of the glutamic acid decarboxylase (GAD), such as semicarbazide, into the dPAG. In this work, we examined whether the expression of these defensive responses could be the result of activation of ventral portion of the periaqueductal gray. Sham- or vPAG electrolytic–lesioned rats were implanted with an electrode in the dPAG for the determination of the thresholds of freezing and escape responses. The vPAG electrolytic lesions were behaviorally verified through a context-conditioned fear paradigm. Results indicated that lesion of the vPAG disrupted conditioned freezing response to contextual cues associated with footshocks but did not change the dPAG electrical stimulation for freezing and escape responses. In a second experiment, lesion of the vPAG also did not change the amount of freezing and escape behavior produced by microinjections of semicarbazide into the dPAG. These findings indicate that freezing and escape defensive responses induced by dPAG stimulation do not depend on the integrity of the vPAG. A discussion on different neural circuitries that might underlie different inhibitory and active defensive behavioral patterns that animals display during threatening situations is presented.     

Role of 5HT1A receptors in a variety of kinds of aggressive behavior in wild rats and counterparts selected for low defensiveness towards man

The 5HT_1A receptor agonist ipsapirone (10 mg/kg) suppressed shock-induced aggression in wild and domesticated rats but did not affect predatory aggression in either group of animals. Ipsapirone decreased neophobia and inhibited defensive reactions by wild rats towards man in the glove test. [³H]8-OH-DPAT binding, which labels 5HT_1A receptors, was significantly increased in the hypothalamus of domesticated rats in comparison with wild counterparts, while 5HT_1A density was unchanged in the frontal cortex in domesticated animals. In essence, the aggressive reactions contributing to the defensive behavior complex in wild rats appear to be regulated through 5HT_1A receptors. © 1992 Wiley-Liss, Inc.     

Phenylpropanolamine inhibits feeding, but not drinking, induced by hypothalamic stimulation.

In rats bearing lateral hypothalamic electrodes that elicited both feeding and drinking, intraperitoneal injection of the appetite suppressant drug phenylpropanolamine (Propadrine) inhibited only feeding. This occurred whether feeding and drinking were tested simultaneously or separately. Selective inhibition of lateral hypothalamic feeding also followed injection of this drug through lateral, but not medial, hypothalamic electrode cannulas. We conclude that hypothalamically induced feeding is under some of the same pharmacological controls as spontaneous feeding, that this control may be exerted, in part, in or near the lateral hypothalamus, and that the neural systems which induce feeding and drinking during hypothalamic stimulation can be pharmacologically separated.     

Aggressive reactions of ducklings to a nonliving target object

This study asked whether ducklings' forceful pecks at a nonliving target object could be validly identified as aggressive. Previously isolated ducklings were exposed to a small cylindrical object that could serve as a target for aggressive pecks and as an object for attachment. After initially attempting to flee from the target, they vigorously pecked at it and also showed signs of the formation of a social (imprinting) attachment. In all important respects this pattern of behavior was identical to the pattern of escape, aggressive pecks, and attachment seen when a previously isolated duckling first encounters a conspecific. Social housing, a manipulation which attenuates aggression against live targets in ducklings and other species, reduced pecking at the nonliving target object. Early aversive stimulation, which enhances aggression against live targets, increased pecking at the object. These findings support the use of nonliving targets in the study of aggression in ducklings.     

Medial preoptic area and onset of maternal behavior in the rat.

The present series of experiments examined whether the medial preoptic area (MPOA) is involved in the onset of maternal behavior in the rat. Previously, the MPOA had been shown to be important in the maintenance of maternal behavior in the lactating rat. The first experiment investigated whether estradiol benzoate (EB) acts on the MPOA to facilitate the onset of maternal behavior in the 16-day pregnant, hysterectomized, and ovariectomized female rat. Such rats when given EB implants in the MPOA had significantly shorter latencies for the onset of maternal behavior than had females implanted with cholesterol in the MPOA or with EB in the ventromedial hypothalamus, in mammillary bodies, or under the skin. A second experiment showed that estrogen-induced prolactin release was not involved in this facilitation. A third experiment indicated that MPOA lesions disrupt the onset of maternal behavior that is induced by pup stimulation in virgin females. It was concluded that the MPOA is involved not only in the maintenance of maternal behavior but in the hormonally mediated onset of maternal behavior and the onset of maternal behavior induced in virgin females by pup stimulation.