Mouse-killing Behavior Research Articles

Manganese loading induces mouse-killing behaviour in nonaggressive rats

Manganese loading induces mouse-killing behaviour in nonaggressive rats

Does manganese excess induce the mouse-killing behaviour in initially nonaggressive rats?

Does manganese excess induce the mouse-killing behaviour in initially nonaggressive rats?

INDUCTION OF FOS-LIKE IMMUNOREACTIVITY IN THE LATERAL HYPOTHALAMIC AREA OF THE RAT AFTER MURICIDE

Serotonergic innervation in the lateral hypothalamic area (LHA) has been implicated in mouse-killing behavior, muricide, of rats. In the present study, functional activation of neurons in the LHA was demonstrated by immunohistochemistry of Fos-protein, a marker of activated neurons, following raphe lesion-induced muricide. Fos-protein induction was seen in the ventral part of the intermediate hypothalamic area (IHA) of the LHA in the muricide rat. Following raphe transplantation into the brain near the bilateral IHA, a significant decrease in the number of Fos-immunoreactive cells was observed in this area, coinciding with decreased muricide behavior. The present results suggest that the decline in Fos-protein expression in this area may be associated with the inhibition of this behavior.

MK-801 suppresses muricidal behavior but not locomotion in olfactory bulbectomized rats: involvement of NMDA receptors

In rats, olfactory bulbectomy (OBX) causes changes in glutamatergic function in the amygdala (AMG) and induces mouse-killing behavior (MKB). The medial AMG (mAMG) plays an important role in the initiation and maintenance of OBX-induced MKB. In the present study, systemic injection or intra-mAMG perfusion of (+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a, d]cyclohepten-5,10-imine hydrogen maleate (MK-801) was used to determine the effects of MK-801, a noncompetitive N-methyl- d-aspartate (NMDA) receptor antagonist, on the expression of OBX-induced MKB in male Wistar rats that had undergone OBX 1 month previously. The effects of MK-801 on locomotion in OBX rats were also examined using the open-field test. Intraperitoneal injection of MK-801 at doses of 0.10 and 0.15 mg/kg resulted in reversible suppression of MKB, the effect being maximal within 1 h after drug treatment, then gradually disappearing over 6 h. Locomotor distance in OBX rats was not affected using 0.10 mg/kg of MK-801, but increased after treatment with 0.15 mg/kg of MK-801; both doses, however, caused the rats to spend longer in the central area of the open field. MKB was also reversibly suppressed by local perfusion of 1 mM MK-801 at a rate of 1 μl/min into the mAMG through microdialysis probes. These results suggest that NMDA receptors, at least, in the mAMG, are involved in the expression of OBX-induced MKB.

Maize Based Diets and Mouse-Killing Behavior in Rats

Mouse-killing behavior is correlated with decrease in brain serotonergic tone, caused by injection of p- chlorophenylalanine (which blocks serotonin synthesis), or by tryptophan free diets,which slow down serotonin production because source of tryptophan is done only by endogenous proteins.Another experimental method is maize exclusive diet:maize is, among cereals, that one which has the lowest tryptophan content, and the lowest value of the ratio between tryptophan and its concurrent amino acids for neuron access. In a lot of experiments, maize based diets gave rise to brain serotonin deficiency and to mouse-killing behavior in previous non killer rats.

Mouse Killing Behaviour, Aggressiveness and the Influence of Sexual Hormones in Rats

“Mouse-killing behaviour” is the behaviour of an isolated adult rat towards an anesthetized mouse placed in its cage; some rats (natural killer) spontaneously kill the mouse, others do not show any kind of aggressiveness.This interspecific aggressiveness, addressed to individuals of different species, is generally motivated by the instinct of predation. It can be distinguished by the intraspecific aggression,which is addressed to individuals of the same species, can have different motivations (establishment of a hierarchy, copulation, defence of territory) and can express itself with threats or real attacks, and can result in a dominant behaviour or in escape or in submission.

Hypothalamic aggression area under serotonergic control in mouse-killing behaviour of rats.

The serotonergic system participates in the modulation of aggressive behaviour. We examined the neuronal substrate underlying serotonergic control of aggressive behaviour in rats using a transplantation technique. Fetal serotonergic neurons transplanted into the hypothalamus restored inhibition of mouse-killing behaviour (muricide), in rats with raphe lesions induced by a serotonergic neurotoxin, 5,7-dihydroxytryptamine. Immunohistochemical and neurochemical studies indicated that the recovery of serotonergic innervation in the lateral hypothalamic area by the raphe grafts brought about the inhibition of muricide. The extension of serotonergic fibres into the lateral hypothalamic area from the grafted serotonergic neurons is strongly related to inhibition of muricide. These results indicate the possibility that serotonergic neurons regulate muricide through the inhibition of the activity of the lateral hypothalamic area neurons.

Aggression and Serotonin. Contribution of Inhibitory Mechanisms.

Transplantation of fetal serotonergic neurons into the hypothalamus restored muricide (mouse killing behavior) in the rat with raphe lesion induced by 5, 7-dihydroxytryptamine (selective serotonergic neurotoxine). Immunohistochemical and neurochemical studies indicated that recovery of serotonergic innervation in the lateral hypothalamic area by the graft brought about the inhibition of muricide. The grafted serotonergic neurons are strongly related to the inhibitory action on the muricide. Transplanted serotonergic neuron system can result in a reinnervation of the host, and leads to a reestablishment of the aggressive behavior.

Measurement of the Three Phases of Muricidal Behavior Induced by Δ9-Tetrahydrocannabinol in Isolated, Fasting Rats

Δ9-Tetrahydrocannabinol (THC) has long been recognized as inducing mouse-killing behavior (muricidal behavior) in starving, isolated rats after a single injection. We showed that when the killing tendency was increased by THC, a preliminary contact with a mouse decreased the probability of muricidal behavior. By quantifying the three phases of the muricidal behavior in either nonkiller or naive THC-treated rats, we showed that the duration of each step was notably increased as compared to untreated natural killer rats, mainly the attack on the dead mouse, indicating increased aggressiveness. Finally, no significant changes were observed in the duration of the three phases in natural killer rats when the muricide assays were repeated every hour. In contrast, in THC-treated rats—either naive or nonkiller—all three phases decreased with the assay repetition to levels comparable to those of natural killer rats, suggesting that the killer behavior was progressively acquired for the six assays. These changes could be a useful model to study the central effects of THC and either its agonists or antagonists.

The role of serotonergic neuron system in the mouse killing behavior (muricide) of the rat

The role of serotonergic neuron system in the mouse killing behavior (muricide) of the rat

Are rats with genetic absence epilepsy behaviorally impaired?

Absence seizures in humans are characterized by unresponsiveness to external stimuli and inactivity. However, in typical generalized non-convulsive epilepsy in children, intellectual capacities are considered to be normal. Wistar rats from an inbred strain with spontaneous absence-like seizures were compared with rats from the outbred control strain in various behavioral tasks in order to detect possible impairments related either to the absence epilepsy or to occurrence of spike and wave discharges (SWD). Spontaneous circadian locomotion, exploratory activity in an open field, social interactions with an unfamiliar conspecific and mouse killing behavior were similar in both strains. Avoidance learning in a shuttle box or food reinforced learning in a Skinner test were unimpaired or even improved in epileptic rats. During performance of a learned task either in the Skinner box or in a conditioned sound-bar pressing task, SWD were suppressed in epileptic rats as long as they were working for reinforcement. SWD reappeared when the motivation to perform the task had declined: unresponsiveness to a conditioned stimulus was then observed during SWD. These data are in agreement with observations commonly described in children with typical genetic absence epilepsy.

In vivo changes in brain catecholamine release from rat hypothalamus following olfactory bulbectomy

The mechanism eliciting mouse-killing behavior (muricide), induced by bilateral olfactory bulbectomy, has been shown to involve the brain noradrenergic system; this is because muricide is specifically inhibited by the drugs which potentiate the activity of catecholaminergic neurons such as tricyclic antidepressants. Our previous reports also demonstrated that the hypothalamic noradrenaline (NA) contents increased in the rats which exhibited muricide. To further examine the hypothalamic noradrenergic function in muricide, a push-pull perfusion technique was applied for direct measurement of NA release from the lateral (LH) and ventromedial (VMH) hypothalamus in freely moving rats. Subsequently, the perfusates, including catecholamines and their metabolites were measured by means of high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Three days after olfactory bulbectomy, 67% of the rats elicited muricide and NA release from LH tended to decrease. Moreover, 7 days after olfactory bulbectomy, most of the rats elicited muricide and NA release from LH was significantly decreased, but not from VMH. On the other hand, dopamine (DA) release from VMH without LH conversely increased on the 7th day after olfactory bulbectomy. These results suggest that the dysfunction of the noradrenergic system caused by the decrease in NA release from LH played an important role for the incidence of muricide.

Inhibition of mouse-killing behavior by S-adenosyl-L-methionine in midbrain raphe-lesioned and olfactory-bulbectomized rats

The effect of S-adenosyl-L-methionine (SAM), a methyl donor, on mouse-killing behavior in rats with lesions of the midbrain raphe nuclei and in olfactory-bulbectomized rats was investigated. Systemic administration of SAM at doses of 180 and 320 mg/kg IP caused a significant inhibition of both kinds of mouse-killing behavior. The inhibitory effects of SAM on both types of mouse-killing behavior were almost equipotent. Microinjection of SAM at 10–100 μg/rat into the lateral ventricle also inhibited mouse-killing behavior induced by raphe lesions in a dose-dependent manner. The ED 50 value of SAM for this effect was 38.6 (18.4–81.4) μg/rat. It is concluded that SAM has inhibitory effects on mouse-killing behavior in both raphe-lesioned and olfactory-bulbectomized rats through a site of action in the central nervous system.

Alterations of serotonin neurotransmission and inhibition of mouse-killing behavior: III Effects of minaprine, CM 30366 and SR 95191

Three closely related aminopyridazine derivatives: minaprine [3-(2-morpholino-ethylamino)-4-methyl-6-phenyl pyridazine, dihydrochloride], CM 30366 [3-(2-morpholino-ethylamino)-4-methyl-6-(4-hydroxyphenyl) pyridazine, hydrobromide] and SR 95191 [3-(2-morpholino-ethylamino)-4-cyano-6-phenyl pyridazine] were examined for their inhibitory effects on mouse-killing behavior (MKB). Three groups of killer rats were used: spontaneous killer rats (K rats) and nonkillers which became killers following para-chlorophenylalanine (PCPA) treatment or electrolytical destruction of the dorsal and median raphe nuclei. When given intraperitoneally (IP), the three drugs inhibited MKB of K rats without sedation. When given orally, miniprine showed no antimuricidal effect in K rats. After chronic IP administration of minaprine, MKB inhibition in K rats decreased after 25 days of treatment, probably because serotonin receptors became subsensitive. Minaprine and SR 95191, a derivative of minaprine, are inhibitors of type A monoamine oxidase (MAO), whereas CM 30366, a metabolite of minaprine, has no effect on MAO activity. SR 95191 displayed a similar MKB inhibition in the three groups of killer rats, and in this respect, it behaved like other type A MAO inhibitors. Minaprine and CM 30366 were less efficient in their antimuricidal effect in PCPA-treated and raphe-lesioned killer rats as compared with spontaneous killer rats. Moreover, the time courses of MKB inhibition by miniaprine did not correlate. The effect of miniaphrine on mKB seemed not related in a simple way to an alteration of serotonin level through MAO A inhibition, and rise the question of an alternative mechanism of antimuricidal action, until now unknown.

Behavior, adrenocortical activity, and brain monoamines in Norway rats selected for reduced aggressiveness towards man

Wild Norway rats were selected over 20 generations for reduced aggressiveness towards man. Selection for this characteristic was accompanied by many physiological changes. Although neophobia was significantly inhibited, and irritable aggression reduced by selection, no changes were revealed in mouse-killing behavior or in intermale aggression. The mean level of 5-hydroxyindole acetic acid in the hypothalamus as well as serotonin (5-HT) content in the hypothalamus, the midbrain and the cortices was higher in the ‘domesticated’ than in aggressive rats. Mean hypothalamic norepinephrine (NE) level also tended to be higher in the ‘domesticated’ animals. The resting corticosterone level and the response of the hypothalamic-pituitary-adrenocortical axis to an emotional stressor or intracerebroventricularly administered 5-HT or NE were decreased in domesticated rats compared to their aggressive counterparts. It is suggested that the diminution of the hypothalamic-pituitary-adrenocortical function as a result of selection for domesticated types of behavior depends, at least partly, on changes in brain monoaminergic systems.

Inhibitory influence of dihydroergosine on the aggressiveness of rats and mice

Fifty mg/kg of ergot alkaloid dihydroergosine (DHESN) inhibited the mouse-killing behavior of isolated male rats, while 10 mg/kg did not. This effect of DHESN (50 mg/kg) lasted for 24 hr. When an additional injection of DHESN (50 mg/kg) was given to mouse-killer rats 6 days following the first, the mouse-killing behavior was again inhibited. The effect of the second drug injection also persisted for 24 hr and was accompanied by an increased concentration of 5-HT in the raphe nuclei and hypothalamus and by a decreased concentration of GABA in the olfactory bulbs. DHESN also inhibited aggressiveness in isolated mice. Two hr following the administration of 10 mg/kg DHESN the fighting was inhibited in 46% of pairs tested, while 50 mg/kg abolished it completely. The effect of 50 mg/kg lasted 24 hr. These results, showing the antiaggressive effects of DHESN, support our previous suggestion that DHESN might presumably be a new antidepressant, and suggest that besides the serotoninergic, the GABA-ergic system might also be involved in the modification of behavior induced by this drug.

Selective increase of offensive behavior in the rat following intrahypothalamic 5,7-DHT-induced serotonin depletion

Cerebral serotonin (5-HT) depletions usually increase aggressive behaviors and more specifically facilitate elicitation of offensive behaviors. In order to localize the brain structures involved in this effect, 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin of 5-HT neurons, was injected into the ascending serotonergic pathway within the lateral hypothalamus, thus depleting 5-HT only in the forebrain structures. The effects of such treatment on offensive and defensive as well as social and non-social behaviors were studied in resident rats confronted with untreated intruders. Pretreatment with desipramine protected noradrenergic neurons. The content of 5-HT fell to 25% of controls, whereas noradrenaline was maintained at 90% in the forebrain anterior to the injection site. Ethological analysis of both resident's and intruder's behavior showed that offensive items were increased in 5,7-DHT-treated residents, whereas defensive items were increased in their non-treated partners; non-social activities were unchanged. Control of mouse-killing behavior during a 2-h test in the same animals showed a clear increase in elicitation of killing in 5,7-DHT-injected rats. These results confirm that the inhibitory control of serotonin is exerted specifically on offensive aggression. They suggest that forebrain structures are involved in this control.

Comparison of the Effects of Benzodiazepine and Nonbenzodiazepine Anxiolytics on Mouse-Killing Behavior in Rats

The present study investigated the effects of nonbenzodiazepine anxiolytics on mouse-killing behavior in rats, compared with the effects of benzodiazepine anxiolytics. Mouse-killing behavior was induced by bilateral olfactory bulbectomy. The following drugs were administered intraperitoneally: chlordiazepoxide, diazepam, ethyl loflazepate, fludiazepam, zopiclone, suriclone, and CL 218,872. Among these drugs, suriclone (ED50=1.3 mg/kg) and fludiazepam (ED50=5.9 mg/kg) showed potent suppressive effects. Diazepam, ethyl loflazepate, and CL 218,872 showed only weak actions on mouse-killing behavior.

Alterations of serotonin neurotransmission and inhibition of mouse killing behavior: II. Effects of selective and reversible monoamine oxidase inhibitors of type A

Three groups of rats were tested for mouse killing behavior after IP injection of selective and reversible type A monoamine oxidase inhibitors. The rats were either spontaneous killers, or non-killers which acquired killing behavior following para-chlorophenylalanine treatment or electrolytical destruction of dorsal and median raphe nuclei. Moclobemide (para-chloro-N-(2-morpholinoethyl)-benzamide), cimoxatone (3-(4-(3-cyanophenyl-methoxy)phenyl)-5-(methoxy) -2-oxazolidinone, MD 780515), toloxatone (5-(hydroxymethyl)- 3-(3-methylphenyl)-2-oxazolidinone) and amiflamine ((+)-4-dimethylamino-2, alpha-dimethylphenethyl amine, FLA 336 (+)) were used as selective and reversible monoamine oxidase inhibitors of type A. Cimoxatone, toloxatone and amiflamine inhibited mouse killing behavior of spontaneous killer rats without apparent sedation, whereas moclobemide was not efficient at doses which did not decrease locomotor activity. A similar inhibition of mouse killing behavior was obtained in spontaneous and serotonin depleted killer rats. The results are discussed in relation to the behavioral expression of serotoninergic supersensitivity in the three groups of killer rats described earlier using serotonin agonist and uptake inhibitors.

Cutaneous lesions in capsaicin-pretreated rats. A trophic role of capsaicin-sensitive afferents?

1. The time course and regional distribution of 'spontaneous' cutaneous lesions in rats desensitized to capsaicin as newborns was correlated to behavioural observations and regional distribution of substance P-like immunoreactivity (SP-LI) and tachykinin-like immunoreactivity (TK-LI) in various skin areas. 2. 'Spontaneous' skin lesions in the form of wounds, scabs and areas of alopecia were observed in 80-90% of rats desensitized to capsaicin. No major sex-related differences were observed with regard to incidence and distribution of the lesions with the possible exception of a lesser tendency to bilateral lesions in female rats. 3. 'Spontaneous' skin lesions were almost restricted to the head: the areas most frequently affected were snouts, periocular and retroauricular regions and ventral area of the neck. 4. No major differences were observed between capsaicin- or vehicle-treated animals in spontaneous or novelty-induced grooming as well as in open-field gross behaviour. Likewise, no differences were observed in the mouse-killing behaviour. 5. Both SP-LI and TK-LI in various skin areas were significantly reduced by systemic capsaicin pretreatment. The rank order of various skin areas for SP-LI or TK-LI levels was: snouts greater than thigh greater than neck greater than abdomen approximately equal to retroauricular region. 6. Intradermal injection of Arg-neurokinin B, a potent and water soluble derivative of neurokinin B, produced a similar plasma extravasation (Evans blue leakage technique) in the skin of vehicle- or capsaicin-pretreated rats. 7. In capsaicin-desensitized rats fur regrowth (measured at abdominal level, 28 days after shaving) was significantly less than in vehicle-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)