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.     

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.     

Visual aspects of centrally elicited attack behavior in the cat: “Patterned reflexes” associated with selection of and approach to a rat

It has been previously suggested that the electrical brain stimulation which elicits quiet-biting attack in the cat actively affects the way the central nervous system processes visual and tactile information concerned with the reflexes involved in the terminal aspects of attack. In order to examine the effects of brain stimulation on a nonterminal aspect of attack – the stimulated cat's selection of and approach to a rat – cats were implanted with attack-eliciting electrodes in both the lateral hypothalamus and the midbrain ventral tegmental area. These cats were then tested in an 8-ft-long cage, one end of which was divided into three, 2-ft-long parallel compartments, whose openings faced the end of the cage from which the cat commenced its approach. An anesthetized rat was placed at the back of one compartment, a bowl of food at the back of another compartment, and the third compartment contained no object. It was found in the first experiment that the attack elicited by nearly all electrodes was selectively directed at the rat. However, the success of the cat in finding the compartment containing the rat varied dramatically for different electrodes in the same cat. Further, these differences were stable and did not change as the cat gained experience with the task. The results suggested that the stimulation of different brain sites in the same cat differentially affected the visual neural mechanisms involved in guiding a cat to a rat. Previous studies have also suggested that the effects of brain stimulation which elicits quiet-biting attack are largely lateralized to the side of the brain stimulated. In order to determine if the effects of stimulation on the neural mechanisms mediating the visually guided approach of a cat to a rat were also lateralized, attempts were made in a second experiment to disrupt the visual input to one side of the brain by unilaterally transecting the optic tract. It was found that this manipulation interfered with the visually guided selective approach to a rat, if the cat was stimulated through hypothalamic or mid-brain electrodes ipsilateral to the optic tract transection, but not if the hypothalamic or midbrain stimulation was on the contralateral (visually intact) side of the brain. However, any final interpretation of the results was confounded by the finding in all of these cats of a complex syndrome of neglect of all contralateral sensory information.     

Enhanced social docility in male hooded rats by dermal cautery of the vibrissal pads

Ablation of the vibrissal pads in rats causes subsequent deposition of scar tissue with little or no regrowth of the vibrissae. Cauterized and intact mature male Long Evans rats were tested for shockelicited fighting, mouse killing, and colony intrusion forms of laboratory-induced aggression. The results revealed that only conspecific social fighting is blocked by ablation of the major vibrissal follicles. Although no significant group differences were noted in tests for mouse killing, shock-elicited paired fighting and territorial defense against a strange intruder were minimal in cauterized groups. The results emphasize the importance of specific sensory experience in reference to distinct forms of aggressive responding and support a new experimental technique for further investigation of sensory interactions with sources of aggressive behavior.     

Dominance-subordinance in cohabiting pairs of adult rats: Effects on Aggressive behavior

Following an initial intruder aggression test, 10 pairs of adult male rats matched on aggressiveness were formed. The first 20 min of paired cohabitation were used to determine dominance and subordinance between pau members. Residents judged to be dominant from this observation session gained significantly more weight during cohabitation and exhibited significantly more aggression on the second aggression test than their subordinate counterparts. Significant correlations among various measures of aggression were found, but open field performance did not correlate, with the measures of aggression nor did changes in open field scores reflect changes in aggression.     

Effects of neonatal treatment with cyproterone acetate on aggressive behavior induced by footshock in adult male rats

High levels of androgens are required to organize aggressive behavior in adult male rats. Footshock-induced aggression was tested in Wistar rats allocated to one of three experimental groups: control (oil-injected) males (M), males neonatally injected with the antiandrogen cyproterone acetate (CA), and males treated as in the CA group but gonadectomized just before puberty (CAG). An antiaggressive effect of CA in those adult male rats neonatally treated with this compound was found. Neonatal exposure to cyproterone acetate exerts an antiandrogenic effect over the expression of shock-induced aggressive behavior. The behavioral effects of CA were not countered by adult treatment with testosterone propionate.     

Mouse killing by rats: Suppression by electrical stimulation ventral to the anterior septum

Killing of mice was suppressed in 18 out of 24 rats by electrical stimulation of the region ventral to the anterior septum lying between the vertical arm of the diagonal band of Broca and the rostral limb of the anterior commissure. The mean effective minimum stimulation intensity was 8.2 uA (60 HZ, RMS). Stimulation of the cingulate cortex did not suppress mouse killing (mean stimulus intensity: 38.7 uA). Electrical recordings revealed after discharge in response to the stimulation in only one animal. At the stimulation intensity which suppressed mouse killing, there was no significant suppression of eating in 6 of 9 animals tested. These results are consistent with other evidence implicating the region ventral to the anterior septum in the modulation of mouse killing in the rat.     

The effect of ethanol treatment on social behavior in male rats

The effect of 0.50 g/kg of EtOH in male rats interacting with a stimulus male juvenile in a newly developed test of social interaction was examined. The adult male rats were treated with EtOH (8.0 to 12.0 g/kg/day) or equicaloric dextrin maltose for 2 weeks (studies 1 and 2) or 8 weeks (study 3) and social interaction was assessed both before and after chronic drug treatment was ended in study 1 and after chronic drug treatment was ended in studies 2 and 3. It was found that prior to chronic drug treatment, in study 1, 0.50 g/kg of EtOH increased both aggressive behavior and time spent interacting with the stimulus juvenile male from the first presentation of the juvenile to the second presentation (20 min apart) while saline injection decreased it. After chronic drug treatment was ended, in study 1 animals treated chronically with EtOH were more aggressive when they were not intoxicated than when they had been treated with 0.50 g/kg of EtOH. In studies 2 and 3, after chronic drug treatment was ended, aggressive behavior and time spent interacting with the juvenile were greater in the animals treated chronically with EtOH, regardless of whether they were injected with saline or 0.50 g/kg of EtOH. The results of these studies showed that chronic EtOH treatment can produce long-lasting changes in social behavior after drug treatment is over and can alter the animal's normal response to EtOH in a social setting.     

Economic substitutability of electrical brain stimulation, food, and water.

Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other.     

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.     

Noninvolvement of testosterone in aggressive defense behavior in the male blind mole rat Spalax ehrenbergi

Blind mole rats (Spalax ehrenbergi) are solitary and aggressive subterranean rodents. Aggressive defense behavior in the mole rat functions to deter neighboring competitors from territory, food, and mates and includes seismic and odor signals. The aim of the present study was to determine whether the aggressive defense behavior displayed by male mole rats is testosterone dependent. Five behavioral variables were taken as being representative of such aggressive interaction: exposing teeth, biting, bulldozing movements of the head, soil blocking, and self‐grooming. We monitored male testosterone levels and aggressiveness throughout the annual cycle, which can be divided into three main climatic periods: cold and rainy (September–February); warm, during which the soil is still moist and easily excavated (March–May); and hot (June–August), when the soil is hard and dry. In a second experiment the effect of endogenous and exogenous testosterone on male aggressive defense behavior was determined before and after castration and following testosterone propionate replacement. We found fluctuations in male testosterone concentrations, with three peaks: in November, May, and August, one in each of the three climatic periods. However, these fluctuations did not correlate with male aggressive behavior, which remained constant throughout the year. Furthermore, because neither castration nor testosterone propionate replacement in castrated individuals affected their defense behavior, we suggest that such behavior in male mole rats is testosterone independent. The continuous excavation and maintenance of the mole rat’s underground tunnel system demands high energy expenditure year‐round and constant defense of territory sites and food caches from intraspecific rivals. Thus, although testosterone may fluctuate as a result of seasonal breeding cycles, constant high levels of aggressive defense throughout the year are crucial for the survival of the male mole rat in its solitary subterranean environment. Aggr. Behav. 27:64–72, 2001. © 2001 Wiley‐Liss, Inc.     

Effects of reactivity to dorsal stimulation and social role on aggressive behavior in laboratory rats

Rats were selected on the basis of reactivity to dorsal tactile stimulation and then tested in a resident-intruder paradigm. While reactivity of residents did not influence the occurrence of agonistic behaviors or wounding of residents and intruders, reactivity of intruders did affect offensive and defensive patterns of interactions and the wounds sustained by residents and intruders. Subsequent to resident-intruder testing, rats were tested for shock-induced aggression. The pattern of the results and the results of additional experiments demonstrated that resident-intruder experience could affect subsequent shock-induced aggressive behavior.     

Female behavior in populations of mice in the presence and absence of male hierarchy

Female aggression may be the regulator of population size in small mammals. Freely growing populations of house mice showed several differences in aggressive female behavior in the presence and the absence of a male hierarchy. Territoriality in females and not in males appeared to maintain social order and regulate population density. Certain females were seen patrolling and guarding the territory and chasing and fighting with both male and female intruders. These females did not fight amongst themselves, suggesting that they were not fighting for rank (as do the males) but for territory. Although these aggressive females produced young, the pups were neglected, and few were weaned. The non-aggressive females were the successful breeders. Aggression by the females only occurred when there was reproduction and increased densities. Assembled females with no males present never show this aggression. The occurrence of “male-type” behavior became most apparent when the males were removed at peak population densities. The removed males were then castrated and injected with testosterone cyprionate. Doses were increased by population cage, and therefore all males returned to each freely growing population were given the same dose. The males given oil placebo injections showed no return of a male hierarchy and the females showed high levels of aggression toward them. Males injected with testosterone cyprionate showed return of male aggression and fighting and mounting of females. But the new “dominant” females continued their patrols and chased males away from their territories and did not permit these males to mount. Male-male fighting consisted primarily of frontal attacks to the face and roll and tumble fights. Female-male aggression consisted primarily of attacks to the posterior region targeted at the base of the tail and the genitals of the male. The males were rarely seen attacking females and then only during mating. Females only attacked each other in defense of their territories.     

Ventral and dorsolateral regions of the midbrain periaqueductal gray (PAG) control different stages of defensive behavior: Dorsolateral PAG lesions enhance the defensive freezing produced by massed and immediate shock

Rats that receive nociceptive electric shock in an environment normally show the conditional fear-induced defensive response of freezing when returned to that environment. If several electric shocks are given in a massed manner they will condition less freezing than the same shocks given in a distributed manner. If a single shock is given immediately after placement in the chamber it does not support any conditioning, although the same shock given after a brief delay does. Electrolytic lesions of the dorsolateral periaqueductal gray (PAG), which damaged dorsomedial, dorsolateral, and lateral PAG, enhanced freezing under these conditions. Lesions of the ventral PAG, which caused extensive damage to the central gray below the aqueduct, reduced conditioning under the more optimal parameters (distributed or delayed shock). This was taken to indicate that both of these regions support different modes of defensive behavior and that when activated, the dorsolateral PAG inbits conditional fear-induced defensive behavior. © 1995 Wiley-Liss, Inc.     

Modifications induced by neonatal steroids in reproductive organs and behavior of male rats.

Male rats injected on Day 3 neonatally with .01, .1, 1, 10, 100, or 1,000 micrograms of estradiol benzoate (EB), 10,000 microgram of testosterone propionate (TP), or sesame oil were subsequently examined for testicular, penile, and accessory organ development. Sexual behavior was evaluated during therapy with fluoxymesterone (FM) and then with TP. Estradiol benzoate in dosages greater than 1.0 micrograms delayed testicular descent, reduced the size and hormone responsiveness of reproductive organs, and decreased sexual behavior in a dose-dependent manner. The 10,000-microgram dosage of neonatal TP delayed testicular descent and reduced sexual behavior to levels near those of the 10--100 micrograms EB groups, but it produced no significant penile or accessory organ changes. Neither reduced peripheral organ development nor inhibited neonatal testicular secretions fully explain reductions in male behavior following large dosages of neonatal TP. Neonatal androgen may reduce the responsiveness of central nervous system neurons governing male sexual behavior after being converted to estrogen or by directly altering steroid receptor systems.     

Effects of losing and testosterone upon subsequent behavior in male and female S3 (Tryon Maze Dull) rats

Attempts were made to determine whether modification of agonistic behavior by experience differs in the sexes and if so, whether testosterone is involved in this response. Gonadectomized male and female CPB-S3 (Tryon Maze Dull) rats were treated with testosterone propionate (TP, 250 μg) or vehicle and subjected to tests in which they became either winners or losers. S3 males and females were tested against Long Evans rats to become losers or against Wistar rats to become winners. Subsequently, S3 winners were tested against losers. In addition, winners and losers were tested against naive S3 opponents of the same sex. After varied agonistic experiences, all animals were tested for social preference in a situation in which they could choose between their respective opponents without the possibility of social interaction. Thereafter, they were also exposed to a two-choice passive avoidance learning procedure to see if the behavioral effects of aggressive interactions generalized to nonsocial learning. Males and females reacted differently to winning or losing, the presence of testosterone being a critical factor in the manifestation of this sex difference. Relatively permanent effects on aggressive and other behaviors were only established in TP-treated males. Losing experiences in the social-preference test generally led to a slight preference for naive, less aggressive animals. Testosterone-treated male losers, the group expected to be most vulnerable to generalized inhibition and impairment of learning, did not differ from other categories in the two-choice passive avoidance procedure, although marked differences were observed between the sexes and between testosterone and oil-treated animals.     

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.     

Amygdaloid function in the central cholinergic mediation of shock-induced aggression in the rat

A series of experiments was designed to examine the role of central cholinergic mechanisms in shock-induced aggression. Cholinergic blockade in the basolateral amygdala, ventral hippocampus, or dorsal hippocampus resulted in greatly reduced levels of fighting in response to footshock. However, while pain sensitivity remained unaltered in the amygdala group, both of the hippocampal groups exhibited decreased shock sensitivity. Further investigation of the amygdala revealed (1) increased fighting in response to increased cholinergic levels, (2) neuroanatomical specificity to the basolateral division of this complex, (3) that an intact basolateral amygdala is essential to the normal manifestation of shock-induced aggression, and (4) that social attraction remains unaltered by cholinergic blockade of the basolateral amygdala. Motor coordination and motor activity were not significantly affected in any treatment condition.     

Neurochemical mechanisms underlying amygdaloid modulation of aggressive behavior in the cat

Studies designed to determine the respective roles of substance P, excitatory amino acids, and enkephalins in amygdaloid modulation of defensive rage behavior in the cat are presented. The basic design of these studies involved three stages. In stage I, cannula electrodes for stimulation and drug infusion were implanted into medial hypothalamic or midbrain periaqueductal gray (PAG) sites from which defensive rage behavior could be elicited. Then, a stimulating electrode was implanted into a site within the medial, basal, or central nuclear complex from which modulation of the defensive rage response could be obtained. Amygdaloid modulation of defensive rage was determined in the following manner: it employed the paradigm of dual stimulation in which comparisons were made of response latencies between alternate trials of dual (i. e., amygdala = medial hypothalamus [or PAG]) and single stimulation of the hypothalamus or PAG alone. Thus, stage I established the baseline level ofmodulation (i. e., facilitation or suppression of defensive rage) in the predrug stimulation period. In stage II, a selective or nonselective receptor antagonist for a given transmitter system was administered either peripherally or intracerebrally at the defensive rage site, after which time the same dual stimulation paradigm was then repeated over the ensuing 180 min postinjection period in order to determine the effects of drug delivery upon amygdaloid modulation of defensive rage. Stage III of the study took place at the completion of the pharmacological testing phase. The retrograde axonal tracer, Fluoro-Gold, was microinjected into the defensive rage site within the medial hypothalamus or PAG, and following a 6-14 day survival period, animals were sacrificed and brains were processed for histological and immunocytochemical analyses for the neurotransmitters noted above. This procedure thus permitted identification of cells within the amygdala which were labeled retrogradely and which were also immunostained positively for substance P, excitatory amino acids, or enkephalin. For studies involving substance P, defensive rage was elicited from the medial hypothalamus and for studies examining the roles of excitatory amino acids and enkephalin, defensive rage was elicited from the PAG. In the first study, facilitation of hypothalamically elicited defensive rage was obtained with dual stimulation of the medial nucleus of the amygdala. In separate experiments, the selective NK₁ non-peptide antagonist, CP 96,345, was administered both peripherally as well as intracerebrally into the hypothalamic defensive rage sites in doses of 0.5-4.0 mg/kg (i. p.) and 0.5-2.5 nmol (i. c.). Following drug delivery, the facilitatory effects of medial amygdaloid stimulation were blocked in a dose- and time-dependent manner in which the effects were noted as early as 5 min postinjection. The maximum drug dose (4.0 mg/kg) employed for peripheral administration resulted in a 42% reduction in the facilitatory effects of the medical amygdala (P < 0.002). This drug, when microinjected directly into medial hypothalamic defensive rage sites at the maximum dose level of 2.5 nmol, resulted in an 84% reduction of the suppressive effects of amygdaloid stimulation (P < 0.5) at 5 min postinjection. In the next study, an N-methyl-D-aspartate (NMDA) antagonist, DL-α-amino-7-phosphonoheptanoic acid (AP-7), was administered either peripherally (0.1-1.0 mg/kg) or intracerebrally (0.2 and 2.0 nmol) into PAG defensive rage sites. Facilitation of defensive rage behavior, which was observed following dual stimulation of the basal amygdala and PAG, was significantly reduced by either route of drug administration in a dose- and time-dependent manner. At the maximum dose level of peripheral administration, AP-7 reduced amygdaloid facilitation of defensive rage by 63% (P < 0.001) for 60 min, postinjection. A smaller (i. e., 19%) but still significant (P < 0.05) reduction in facilitation was obtained following intracerebral administration of the drug. In a third study, the non-selective opioid receptor antagonist, naloxone (27.5 nmol), infused directly into PAG defensive rage sites, totally blocked the suppressive effects of central amygdaloid stimulation for a period of 30 min (P < 0.05) in a dose- and time-dependent manner. The anatomical phase of this study revealed the following relationships: 1) that large numbers of neurons projecting to the medial hypothalamus from the medial amygdala immunoreact positively for substance P; 2) that neurons projecting to the PAG from the basal complex of amygdala immunoreact positively for glutamate and aspartate; and 3) that neurons located within the central nucleus of the amygdala which project to the PAG immunoreact positively for met-enkephalin. Collectively, these observations provide new evidence which characterizes the likely neurotransmitters linked with specific amygdaloid pathways subserving the modulation of defensive rage behavior in the cat.