Nonkiller Rats Research Articles

Effects of incisor-cutting on muricidal behavior induced by olfactory bulbectomy in rats

Muricidal behavior in rats is composed of two main components, attacking and killing performance. Since a large number of mice could be killed by rats during behavioral experiments, research has been limited in the past decade possibly because of ethical considerations. In preliminary studies, we found that the rat incisors play a key role in muricidal behavior in rats, so, in the present study, we cut off the incisors and assessed the following parameters of muricidal behavior: attack latency, first attack site, lethal attack site, attack frequency, total attack duration and mean attack duration. If after incisor-cutting (IC) rats still tried to demonstrate muricidal activity, but failed to kill the mouse, this would be an ideal model for studying the mechanisms of muricidal behavior. Since muricide can be induced in rats by olfactory bulbectomy (OBX), young adult male Wistar rats with OBX displaying muricidal behavior were tested for muricidal activity 4 h after IC, then every 24 h for 3 days. At 4 and 28 h after IC, only 9% and 36% of rats killed mice, but these values rose to 73% and 82% 52 and 76 h after IC, respectively. At 4, 28 and 52 h after IC, there was no significant difference in attack latency, first attack site, lethal attack site or mean attack duration between IC-treated rats (both killers and nonkillers) and sham-operated controls, while the attack frequency was obviously increased in IC nonkiller rats, and a significantly longer total attack duration was seen in both IC killer and nonkiller rats compared to controls. Since IC treatment increases attack frequency and prolongs the total attack duration without affecting other basic components of muricidal behavior in rats, these results suggest that the killer rats treated with IC may provide a suitable model for research on muricidal behavior.

Behavioral reactivity following 5-MeODMT administration in 5,7-DHT-pretreated killer rats

Grouped, nonkiller and killer animals were centrally injected either with vehicle or with 5,7-dihydroxytryptamine. After a period of 7-10 days, forepaw treading and hindlimb abduction were induced by 5-MeODMT administration in all sham and lesioned rats. As expected, behavioral supersensitivity was observed in grouped and nonkiller lesioned rats. A reduced increase in 5-MeODMT-induced behaviors was obtained in killer lesioned animals. 5-HT uptake studies showed a comparable reduction of 5-HT uptake within all the lesioned rats. This evidence suggests an altered capacity to promote adaptive changes on 5-HT sites in killer rats following the destruction of central serotonergic fibers.

Modulatory actions of benzodiazepine receptor ligands on agonistic behaviour

Several experiments were conducted to establish the role of benzodiazepine (BDZ) receptor ligands in aggressive behaviour in male and female rats. In particular, the pro-aggressive effects of BDZ agonists was subject of investigation. Predatory aggression (mouse killing) was facilitated by chlordiazepoxide (CDP) when tested in naive female rats, but CDP was unable to induce muricide in non-killing rats with extensive experience with mice. In experiments on maternal aggression in rats a post-hoc analysis revealed that the pro-aggressive action of CDP on maternal aggression was base line dependent: the increase in aggression in spontaneously low aggressive females was significantly higher than in females with a higher base line level. A further study aimed at unravelling the underlying factors contributing to this pro-aggressive action by determining the role of opponent size on the effects induced by CDP. Normally large opponents evoke less aggression from lactating females than smaller opponents and CDP exerted its pro-aggressive effect particularly strongly in the ‘large opponent’ situation. An ethological analysis was made of lateral display—an ambivalent posture frequently occurring in agonistic behaviour—to establish whether CDP indirectly increases aggression by reducing fear by means of its anxiolytic properties. The data partly support this hypothesis. These findings stress the importance of environmental and experiential factors in the possible outcome of CDP effects on aggression. Moreover, they point to possible explanations of seemingly contradictory data. In two final experiments an inverse benzodiazepine receptor agonist (β-CCE) was tested in maternal aggression. β-CCE reduced aggression, although not in a completely specific way. A neutral BDZ-receptor antagonist (Ro 15-1788) was tried in an attempt to antagonize the pro-aggressive effects of CDP in maternal aggression. Ro 15-1788 did not counteract the pro-aggressive action of CDP, but antagonized CDP effects on exploration. The modulatory role of the benzodiazepine receptor complex in aggression remains an intriguing area of research in which many subtleties in testing conditions play a role and in which more BDZ agonists, inverse agonists and antagonists have to be tested.

Little oscillation of daily food intake in mousekiller rats as opposed to nonkiller rats before any confrontation with mice

During 46 consecutive days the daily food intake and weight were recorded in 16 male Wistar rats. On Days 31-45 one mouse was presented each rat daily. Before any experience with mice (Days 0-27) the mousekiller rats, compared with the nonkiller rats, regulated their individual food intake more closely to their homeostatic equilibria, corrected for the linear trend. This result indicates a functional difference in food intake regulation between mousekiller rats and nonkiller rats prior to any experience with mice. However, no difference in the mean food intake was found between the mousekiller and the nonkiller rats.

Induction of mouse-killing in the rat by intraventricular injection of a GABA-Agonist

Intracerebroventricular injections of THIP (2.5 and 5.0 μg in 5 μl) facilitated elicitation of mouse-killing in killer rats placed in a non-familiar environment. The same doses induced well organized mouse-killing responses in 60% of non-killer rats. Concomitantly food intake was elicited. Exploratory activity as well as orientation and approach towards any sensory stimulus were also increased. On the contrary, intracerebroventricular injections of bicuculline methiodide (65 and 125 ng in 5 μl) suppressed aggressive responses in killer rats. The data support the view that GABA receptors are involved in mechanisms which facilitate elicitation of mouse-killing behaviour as well as other positively motivated responses.

Relationship between mousekilling and conspecific aggression in the male rat

In order to investigate the relationships between mousekilling and conspecific aggression, behavioral variables of killer and nonkiller rats were compared in a “resident-intruder” paradigm, in resident as well as in intruder animals. The occurrence of offensive items (offensive sideways, attack) was significantly higher in killer rats when they were residents; their corresponding opponents displayed more defensive behaviors. No significant difference in aggressive behaviors was noted when the comparison was done in the intruders. These results and those of previous studies suggest that there is a correlation between mousekilling and intraspecific offensive behaviors. Some similarities in the situations where both behaviors are elicited–eg, introduction of an unfamiliar intruder into a familiar environment–may contribute to the existence of such a correlation and the possibility of common mechanisms underlying both behaviors is discussed.

The effect of nomifensine on the muricide induced by thiamine deficiency

We reported that the muricide response induced by thiamine deficiency was inhibited by the administration of 5-HTP and significantly enhanced by p-CPA.Therefore, it was suggested that this response may be related to the brain serotonergic system. On the other hand, the muricide responses were demonstrated to be involved in the brain dopaminergic system; methamphe-temine inhibited the muricide induced by thiamine deficiency, and the muricide response induced by tetrahydrocannabinol was reduced by 1-dopa or amantadine. So, we investigated the effect of nomifensine which inhibited selectively re-uptake of dopamine compared with other antidepressants on the muricide response induced by thiamine deficiency. Male Wister rats(75-85g) were used in this study and supplied with a thiamine deficient diet for 28 days. The occurrence of the muricide was observed between the 14th day and 28th days. Only killer rats were used in the present experiment. It was observed whether the killer rats treated with each of the drugs killed a mouse or not. When 1-dopa(i.p.) or nomifensine(i.p.) was administered for 7 days, the occurrence of muricide was significantly reduced. Furthermore, killer rats treated with nomifensine(i.p. or i.c.v.) or dopamine(i.c.v.) were converted into non-killer rats. Accordingly, it was shown that the drugs had an inhibitory effect on the muricide that was induced by the tiamine deficiency. However, the muricide behavior was not changed by the combined administration of nomifensine(i.c.v.) or dopamine (i.c.v.) after injection of desipramine(i.p.) and 6-hydroxydopamine(i.c.v.). These results indicated that this muricide response may be related to the brain dopaminergic system.

Mouse-killing and hyperemotionality in rats induced by three different kinds of experimental manipulations: A comparative study

Male rats were subjected to one of three different kinds of manipulations: isolation housing, bilateral olfactory bulbectomy, and Δ9-tetrahydrocannabinol (THC) administration. All three treatments produced an increase in the tendency toward mouse-killing behavior and also affected the animal’s emotionality. Each of these treatments, however, produced distinctive features in both the topography of killing response and hyperemotionality. Among the three models, isolation-induced killer rats exhibited the most well-organized killing response, while in both olfactory bulbectomy and THC-induced killer rats the killing response was characterized by inefficient, compulsive, and indiscriminate biting. The satiation of mouse-killing behavior did not occur in any of the three models. Isolation-induced killer rats were more reactive in startle response than were nonkiller rats, while THC-induced killer rats showed a higher reactivity to the presented wooden rod than did nonkiller rats. In olfactory bulbectomized rats, there was no significant difference in any behavioral items between killer and nonkiller rats. This evidence suggests that the mouse-killing behavior in rats is not a unitary phenomenon and that various physiological and psychological bases exist, depending upon the manipulation employed.

Regional changes in brain cholinergic enzyme activities after bilateral olfactory bulbectomy in relation to mouse-killing behavior by rats

Bilateral olfactory bulbectomy produced the increased tendency of mouse-killing behavior in nonkiller rats (60% on the 14th day after surgery). Scopolamine hydrobromide (4 and 8 mg/kg, IP) significantly suppressed the killing response in a dose-dependent manner, whereas methylscopolamine nitrate was ineffective. In order to investigate a possible neural mechanisms, choline acetyltransferase (CAT) and acetylcholinesterase (ACh-E) activities were measured in 7 discrete brain areas: cortex, amygdala, hypothalamus, thalamus, tegmentum, hippocampus, and pons plus medulla oblongata. Although the central anticholinergic drug suppressed mouse-killing, no significant difference in either CAT and ACh-E activities was found between the killer and nonkiller rats in any of the brain areas determined in this study. The evidence suggests that the neurochemical findings may not fit the pharmacological findings for supporting a unified cholinergic hypothesis for mouse-killing behavior.

Regional changes in brain norepinephrine content in relation to mouse-killing behavior by rats

Three separate series of experiments were conducted as follows: isolation housing, bilateral olfactory bulbectomy, and Δ 9-tetrahydrocannabinol (THC) administration. All three experimental manipulations produced an increase in the incidence of mouse-killing behavior. In order to elucidate the possible neural mechanisms mediating the killing response, norepinephrine (NE) content was measured in 6 discrete areas of the brain (the cortex, striatum, amygdala, midbrain, hypothalamus, and pons plus medulla oblongata). Following isolation housing, no significant difference in NE levels of any of the brain areas was demonstrated between the aggregated and isolated rats, nor between the killer and nonkiller rats. The rats with olfactory bulbectomy exhibited high NE content in the hypothalamus as compared with the intact or sham-operated rats, but there was no significant difference between the killer and nonkiller rats. After injection of THC, NE content in both the hypothalamus and pons plus medulla oblongata was decreased independent of the manifestation of killing response. The evidence indicates no regional change in brain NE levels specific to the killing response and suggests that brain NE may not participate in the mediation of mouse-killing behavior.

5,7-dihydroxytryptamine-induced mouse killing and behavioral reversal with ventricular administration of serotonin in rats

In order to establish a more complete behavioral profile on animals induced to kill mice following serotonin depletion, naturally non-mouse-killing male Long-Evans rats were administered 5,7-dihydroxytryptamine (5,7-DHT) in a saline-ascorbic acid vehicle or vehicle alone to the left lateral ventricle through a chronically indwelling cannula. Following a postsurgical delay, animals were tested for mouse killing, food and water consumption, spontaneous motor activity, and exploratory behavior. 5,7-DHT treatment resulted in a significant increase in the incidence of mouse killing over vehicle-injected controls in the absence of effects on the other behaviors investigated. In a second experiment, 5,7-DHT-treated rats from Experiment I were administered small doses of serotonin intraventricularly. An additional group of spontaneously mouse-killing rats also received intraventricular injections of serotonin. This manipulation led to a significant increase in the latency of both groups to kill mice over both preinjection latencies and vehicle-injected control animals. Since serotonin depletion resulted in the induction of mouse killing in naturally nonkilling rats without affecting other potentially contributory behaviors and since the mouse killing could be reversed by intraventricular administration of serotonin an inhibitory role for serotonin in the mediation of mouse killing is suggested.

Induction du comportement d'agression Rat-Souris par la p-chlorophenylalanine: Rôle de l'amygdale

A PCPA injection (300 mg/kg IP, 3 days before behavioral testing) to naive non pretested rats induced mouse-killing in 74% of the rats, the Wistar strain used comprising approximately 10% of spontaneous mouse-killers. The same PCPA injection induced mouse-killing in only 5% of pretested non-killer rats. Thus, familiarization with mice prevents later elicitation of mouse-killing in PCPA treated rats. Lesions of the amygdala and to a lesser extent, lesions of the stria terminalis abolish this suppressing effect of familiarization and thus facilitate elicitation of mouse-killing in previously non-killer rats. This result confirms the involvement of amygdaloid nuclei and efferent pathways in the suppression of a specific aggressive behavior, namely mouse-killing, on the basis of previous non-aggressive experience with the mouse, this mechanism being unaffected by a cerebral serotonin depletion.

Manipulations of dietary tryptophan: Effects on mouse killing and brain serotonin in the rat

Maintaining rats on a tryptophan-free diet for 4–6 days induced mouse killing in non-killer rats, and significantly facilitated killing in killer rats, as indicated by shorter latencies to kill the mice. The killing responses were similar in topography to the natural killing responses. These changes in killing behavior did not appear to be due to generalized changes in irritability. The increased killing after maintenance on a tryptophan-free diet was accompanied by a 26% reduction in brain serotonin (5-HT) and a 29% reduction in brain 5-hydroxyindoleacetic acid (5-HIAA). When the tryptophan-free diet was supplemented with l-tryptophan (0.5 or 2%), brain 5-HT and 5-HIAA were increased above control levels, and the rat's killing response appeared normal both in terms of latency and topography, similar to that seen in control chow fed animals. While rats consumed less of the tryptophan-free and tryptophan supplemented diets, control subjects deprived of chow such that they lost as much weight as rats fed the tryptophan-free diet, did not show changes in killing behavior. These results are consistent with the hypothesis that central serotonergic systems exert inhibitory control over mouse killing behavior in rats.

Induction of mouse-killing in nonkiller rats by temporary chemical lesions in the medial hypothalamus

Male rats which could not be induced to kill a mouse by 120 h of food deprivation had bilateral cannulas implanted into the medial hypothalamus. All rats were tested for muricide 7 to 10 days later while part of the medial hypothalamus was made nonfunctional by an intracranial infusion of the local anesthetic, lidocaine (2% son; infusion rate: 1 /μ1/3 min to each side to a maximum of 3 μ1 bilaterally). Fifty percent of the animals were induced to kill by the infusion. In a group of unselected animals, a similar proportion of animals were induced to kill by the infusion. It is suggested that the induction of muricide by medial hypothalamic infusions is not limited to the facilitation of muricide in animals with a substantial predisposition to kill.

The role of the dorsal and median raphe in the inhibition of muricide

Previous work has implicated the putative neurotransmitter serotonin in the inhibition of muricide. This study examined the possibility that the nuclei of the mesencephalic raphe function differentially in the control of this behavior. The results indicate that radiofrequency lesions confined to the dorsal raphe are sufficient to produce muricide in naturally non-killing rats. Lesions of the median raphe do not produce attack. Evidence is presented that suggests that the region of the tegmentum juxtaposed to the dorsal raphe and central gray contains neural mechanisms necessary for the final behavioral components of the attack sequence.

A comparison of killer and nonkiller rats

Two experiments were performed on Long-Evans rats. The first study was designed to evaluate possible differences in muricidal behavior between killer and nonkiller rats following OB lesions. No significant differences in muricidal behavior were found after OB damage in either group. Experiment 2 examined the behavior of killer and nonkiller rats on reactivity to handling, open-field activity divided into the number of squares traversed and rearing, learning of a visual discrimination task, and learning of an olfactory discrimination task. Killers were found to be less reactive to handling, while exhibiting greater horizontal activity in the open-field test. No other differences were found.

Carbachol-elicited mouse-killing in the rat: Animals attacked and wound location

Mouse-killing was elicited in naturally nonkiller rats by bilateral injections of carbachol into the lateral hypothalamus. These carbachol-converted killers also attacked rat pups and adult rats during the period of drug action. The wounds were distributed more widely over the bodies of mice attacked by carbachol-converted killers than by natural killers. These data suggest that carbachol-elicited killing is similar to affective or irritable aggression.

Biochemical correlates in mouse-killing behavior of the rat: Prolonged isolation and brain cholinergic function

After 30 days of isolation, 45% of the rats exhibited mouse-killing behavior. The killing response was suppressed by atropine (5 mg/kg and 8 mg/kg, IP) and scopolamine (8 mg/kg, IP), whereas methylatropine was ineffective. Acetylcholine (ACh) content and acetylcholinesterase (AChE) activity were measured in 5 discrete areas of rat brain. As compared with the aggregated rats only the killer rats exhibited higher ACh levels in the diencephalon. The activity of AChE in all brain areas was unchanged by isolation; no significant difference was found between the killer and nonkiller rats. These results suggest that central cholinergic mechanisms participate in the mediation of mouse-killing behavior in the rat.

Déclenchement de réactions d'Agression interspécifique par lésion septale après lésion préalable de l'amygdale, chez le rat

In spontaneously nonkilling rats, septal lesions induce the initiation of mouse-killing behavior whenever a prior lesion of the medial part of the amygdala was performed 3 months earlier. The lesion elicits the characteristic septal hyperreactivity, as the animals have recovered from the opposite effect of the amygdaloid lesion after that prolonged delay. The initiation of interspecific aggressive behavior by septal lesions in intact nonamygdalectomized rats depends on the degree of preoperative familiarity with the mouse. As a matter of fact, septal lesions induce by themselves very few aggressive reactions in previously nonkilling rats. The amygdaloid lesion abolishes the capacity to develop a stable inhibition of the killing behavior on the basis of repeated contacts with a mouse. These results confirm that the amygdala is involved in the development and maintenance of a specific behavioural inhibition in the nonkilling rat.

Reserpine induction of mouse killing in nonkiller rats

Seventy-five nonkiller male rats were divided into two groups, 38 animals receiving 3 mg/kg reserpine and the other 37 receiving saline. Fifty percent of the reserpine-treated animals showed mouse killing, whereas none of the other animals did so. Mouse-kill responses were already exhibited within 32 h after treatment, while the animals were still heavily sedated.