Hyperreactivity, muricide, and intraspecific aggression in the rat produced by infusion of local anesthetic into the lateral septum or surroundng areas.

Intracranial infusions of a local anesthetic (lidocaine, 2%) were made bilaterally (4 μl over 20 min) through permanently implanted cannulas ending in the lateral septum or adjacent areas in 167 male hooded rats. Increases in irritability and reactivity to the experimenter, muricide, and intermale aggression were produced by injections into the lateral septum and the region ventral to it. The increase in reactivity and interanimal aggression occurred in varying degrees and were independent of one another, but intermale aggression occurred only in Ss showing muricide. The most effective site for eliciting the entire spectrum of aggressive behaviors was the region ventral to the anterior septum. The region ventral to the posterior septum tended to produce a high incidence of muricide with only modest increases in reactivity. No changes in behavior were noted with infusions into the medial septum or the medial forebrain bundle/lateral preoptic area ventrolateral to the septum. It is suggested that the hyperreactivity and irritability may be related to hyperdefensiveness and that muricide and intermale aggression are points on a continuum of interanimal aggressiveness. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GABAA receptor signaling in the lateral septum regulates maternal aggression in mice.

Maternal aggression (maternal defense) is a fierce aggression produced by lactating females toward intruders that plays an important role in protection of vulnerable offspring. Enhancement of GABAA receptor signaling by benzodiazepines increases maternal aggression, and we recently found indirect evidence that lateral septum (LS) could be a key site where benzodiazepines elevate aggression. In this study, we directly tested the hypothesis that activation of GABAA receptors in LS would promote maternal aggression while inhibition of this receptor would decrease aggression. Site-directed injections to LS were made using the GABAA receptor antagonist, bicuculline (3–30 ng), or the GABAA receptor agonists, chlordiazepoxide, a benzodiazepine (2.5–5 μg), and muscimol (0.05–5 ng). Maternal aggression and other behavioral measures were then evaluated in lactating mice. Neither GABAA receptor agonist elevated aggression, which could reflect a ceiling effect. However, 7 ng of the GABAA receptor antagonist, bicuculline, in LS significantly decreased maternal aggression without altering other maternal behaviors or light-dark box performance, suggesting some GABAA receptor signaling in LS is required for full maternal aggression expression. Together, these results confirm a role for GABAA receptor signaling in LS in the regulation of maternal aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of intermale aggression in mice through exposure to receptive females.

Examined intermale aggression after different exposures to receptive females. In Exp I, socially isolated or grouped CD-1 and Swiss-Webster mice each confronted a target male after either no exposure to or 3 intromissions with an estrous female. High levels of aggression were observed in isolated males after exposure to a female, provided the female was removed when the target male was introduced. In Exp II, variation of duration and quality of exposure to females indicated that aggression increased with more advanced prior sexual activity. In Exp III, sexual activity was not greatly influenced by prior aggressive activity. These data suggest a preparedness to fight following sexual activity, but a prepotence of sexual activity over aggression. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Urocortin 1 and 3 Impair Maternal Defense Behavior in Mice.

Lactating female mice fiercely defend offspring while exhibiting decreased fear and anxiety. Recent work (J. S. Lonstein & S. C. Gammie, 2002) found that intracerebroventricular (icv) injections of corticotropin releasing factor (CRF), a putative anxiogenic peptide, inhibit maternal defense behavior. This study examines effects of CRF-related peptides, urocortin (Ucn) 1 and Ucn 3, on maternal aggression in mice. Intracerebroventricular injections of both Ucn 1 (0.2 μg) and Ucn 3 (0.5 μg) reduced aggression but not pup retrieval. c-Fos levels were elevated by intracerebroventricular injections of Ucn 1 (0.2 μg) and Ucn 3 (0.5 μg) in 2 and 6 brain regions, respectively; however, both triggered increases in bed nucleus of the stria terminalis dorsal (BNSTd) and lateral septum (LS). These findings suggest that CRF-related peptides similarly modulate maternal aggression and that BNSTd/LS may be critical sites for negative regulation of maternal aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

22-28 kHz ultrasonic vocalizations associated with defensive reactions in male rats do not result from fear or aversion

This study was carried out to determine whether 22-28 kHz vocalizations emitted during intermale interactions in adult rats were related with a state of fear, aversion or resulted from painful stimulation. Vocalizations in the 22-28 kHz range were measured in male rats during non-aggressive and aggressive social interactions; when given foot shock with a partner; during non-aggressive social interactions after an injection of (i) acetic acid (1%, IP); (ii) pentylenetetrazol (20-30 mg/kg, IP) and (iii) lithium chloride (63.8 mg/kg, IP). Ultrasonic vocalizations were consistantly detected in all rats while the animals displayed defensive or submissive postures when tested as intruders confronted with offensive residents or when administered foot shocks. Only occasional vocalizations were emitted, even in the presence of a partner, when the animals had received other painful or aversive treatments. These data support the hypothesis that 22-28 kHz vocalizations during intermale interactions are associated with defensive postures and are not the consequence of a state of fear or aversion.     

Copulation and intermale aggression in rats.

Exp I observed attack behavior of 9 reliably aggressive male Long-Evans rats against unfamiliar male intruders immediately following copulation to one or more ejaculations. Copulatory series to 5 ejaculations did not differ from copulation to a single ejaculation or from a noncopulatory control in affecting aggressive behavior. Repetitive biting attacks occurred in all conditions, with comparable wounding. Evidently, the male postejaculatory state of insensitivity to sexual stimuli does not extend to stimuli eliciting intermale aggression. A 2nd experiment determined the attack-eliciting capacity of foreign males placed in the home cage of an actively copulating S. As intromissions increased and the interval to ejaculation decreased, the probability of intermale aggression and interruption of copulation diminished. Findings suggest that a postejaculatory mechanism for behavioral inhibition exists in the male rat, preventing his interference with fertilization but without affecting his capacity to prevent other males from attempting to displace the fruits of his labors. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The participation of the brain dopamine D1 and D2 receptors in the process of the development of depression induced by social confrontations in mice

Brain D1 and D2 receptors were studied in male mice with repeated experience of social defeats in daily intermale aggressive confrontations inducing development of experimental depression. Groups of animals were studied after 10 (T10 losers) and 20 (T20 losers) days of agonistic confrontations. Mice after 5 days of individual housing were used as a control group. In the experimental groups D1/D2 antagonist cisfluphentixol (0.2 mg/kg) did not affect the communicative behavior in the partition test that estimated behavioral reactivity of a male to another one. Selective D2 antagonist sulpiride (20 mg/kg), however, decreased these reactions in the control group and, in particular, in T10 losers but was ineffective in T20 losers. Both antagonists changed behavior in Porsolt's test of the control mice and, to a greater extent, of T10 losers but failed to change it in T20 losers. Decrease in Bmax in nucleus accumbens and increase in Kd in amygdala were revealed in T20 losers with [3H]-SCH 23390 binding assay. The obtained evidence shows that development of DISC is accompanied by D1 and D2 receptor sensitivity changes. Analysis of data suggests the specific participation of D1 receptors of the mesolimbic dopaminergic system at the stage of developed DISC.     

The expression of the molecular chaperone calnexin is decreased in cancer cells grown as colonies compared to monolayer

Nitric oxide acts as a neural messenger in both the central and peripheral nervous systems. Mice with targeted disruption of the neuronal isoform of nitric oxide synthase (nNOS - / -) are extremely aggressive relative to wild-type (WT) mice. Male nNOS - / - mice exhibit an increase in the number and duration of aggressive encounters compared to WT animals when tested in a variety of paradigms used to test rodent aggression. This inappropriate aggressive behavior has only been observed in male nNOS - /- mice; nNOS - /- females, like female WT mice, exhibit little or no aggression. The present study sought to test the dependence of increased aggressive behavior in nNOS - / - males on testosterone. Intact nNOS - / - males exhibited elevated levels of aggression relative to intact WT males. Castration reduced aggression in both WT and nNOS - /- males to equivalent low levels. Testosterone replacement restored aggression to precastration levels in both genotypes. These data provide evidence that increased aggressive behavior of nNOS - /- mice, like aggression in WT mice, is testosterone-dependent.     

The effect of the repeated experience of aggression in daily confrontations on the individual and social behavior of male mice

The influence of repeated experience of aggression in daily intermale confrontations on individual and social behaviour was studied in male mice of C57BL/6J (C57) and CBA/Lac (CBA) strains. Repeated experience of aggression led to a decrease of emotionality in males of highly emotional CBA strain and increase in exploratory activity in the open field and exploratory activity tests, decrease of immobility time in Porsolt's test and pain sensitivity estimated by the "hot plate" test. Low emotional C57 males did not change their individual behaviour in different situations under the influence of repeated experience of aggression. However, aggressive C57 mice demonstrated anxiety-like behaviour estimated in the plus-maze test. In the partition test aggressive mice of both strains showed an increase in communicative level (as a reaction to a familiar male) in comparison with their behaviour before aggressive confrontations. Behavioural reaction to a receptive female under unfamiliar conditions decreased which testified to a decrease in sexual motivation. It is concluded that formation of the aggressive type of social behaviour is accompanied by changes in the individual and social behaviour of male mice. Characteristics of these changes are genetically determined and depend on the duration of confrontations.     

Waning and recovery of conspecific agression in the house mouse (Mus musculus L.).

Reports results of 3 experiments with a total of 254 wild, C57/BL6, and DBA/2 mice. 4-hr exposure to fighting opportunities depressed intermale mice to a low baseline level. A subsequent 18-hr restriction in fighting opportunities restored aggression to its previous level. The time course of these effects was the same whether aggression was measured as the proportion of time spent fighting, trial length, or attack-reinforced barpressing rates. Replacing familiar intruders with novel intruders failed to affect baseline aggression, aggressive waning, or aggressive recovery. Waning and recovery effects replicated across the outbred wild stock of mice and the aggressive inbred strain (C57/BL6) but failed to replicate with the relatively nonaggressive inbred strain (DBA/2). (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic mechanisms controlling the domestication of a wild house mouse population (Mus musculus L.).

A controlled reenactment of the domestication process provided information on the relative effects of natural selection, inbreeding, and habitat upon an originally wild house-mouse population. Effects were assessed in 2 experiments by testing offspring that were bred under either laboratory or simulated natural conditions, systematically inbred or outbred, and postnatally fostered in laboratory or simulated natural habitats. Ss were a total of 100 male laboratory C57BL/6J, DBA/2J, and A/J mice, and 372 mice descended from wild mice. 10 generations of domestication failed to reveal any behavioral differences due to either natural selection or habitat on 9 different behavioral tests. Inbreeding strongly reduced intermale aggression, partially reduced resistance to recapture by humans, and failed to affect any of the 7 other behaviors. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Paternal stimulation during infancy: Effects upon aggression and open-field performance of mice.

Studied aggression in random-bred albino Tuck TT strain male mice from 1st matings, reared by both parents (n = 13) and from 2nd matings, reared only by the mother (n = 15). Prolonged isolation from weaning induced more aggression in Ss from 1st matings than in Ss from a 2nd mating. In a 2nd experiment, fathers of 40 Ss were removed (a) shortly after mating, (b) at the litters' birth, or (c) at weaning. In offspring isolated from weaning, Ss in condition c were significantly more aggressive than those in a, while those in b showed an intermediate response. These differences did not occur when the period of isolation was broken by 50 days of communal housing before aggression testing, although Ss in c defecated more in the open field. It is suggested that young mice "imprint" toward the same odors of adult males which in later life elicit intermale aggression. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of human chorionic gonadotropin on methotrexate concentration in the rat testes

PURPOSE: We analyzed the effect of human chorionic gonadotropin (hCG) on drug concentrations in testicular interstitial fluid and whole testis tissue samples in rats receiving hCG prior to methotrexate (MTX) administration and in animals that did not receive hCG. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were injected subcutaneously with 200 i.u. hCG (Goldline Laboratories, Ft. Lauderdale, FL.). Controls were injected subcutaneously with normal saline (0.2 cc). Sixteen hours after injection, each rat was given methotrexate (Methotrexate LPF, Immunex Corp. Seattle WA.) via a carotid artery cannula in a dose of 30 mg./kg. Methotrexate (MTX) levels were collected 60 minutes post infusion time in 27 rats and 90 minutes post infusion in 27 rats. MTX levels were measured in serum, testicular interstitial fluid and testicular tissue. MTX levels were measured using high performance liquid chromatography (HPLC). RESULTS: A significantly higher concentration of MTX was found in testicular interstitial fluid (TIF) in rats injected with hCG when specimens were collected 60 minutes post infusion. MTX levels in TIF had reversed 90 minutes post infusion with higher levels found in control rats. Tissue levels of MTX demonstrated no significant difference at either 60 or 90 minutes in the hCG treated animals or controls. CONCLUSION: Our results suggest that hCG effects the tissue distribution of MTX within the testis. Human chorionic gonadotropin may have this effect on the testicular microvasculature by 1) selectively increasing capillary permeability, 2) increasing lymphatic flow within the testes or 3) increasing testicular blood flow.     

Dominance in intermale encounters and subsequent sexual success in mice.

In Exp I, when previously isolated male CD-1 mice (n?=?26) were paired and given a female, they fought before beginning to mount, and the more aggressive male ejaculated somewhat more frequently. Males housed together (n?=?26) for several days showed little aggression when jointly given a female, but those that were more aggressive in the home cage clearly ejaculated more frequently. In Exp II, with 144 Ss, males were paired for 4 days after a period of isolation. More aggressive males showed more ejaculations when subsequently tested individually with females, but not when pair members conjointly encountered females. In Exp III, 60 males were paired for several weeks before encountering females. In cases in which home cage dominance was constant, the more aggressive males ejaculated more frequently both when tested individually and when tested as pairs. Findings indicate that success in reproductive behavior in mice is contingent on dominance in intermale aggressive encounters. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alterations in kappa opioid receptor mRNA levels in the paraventricular nucleus of the hypothalamus by stress and sex steroids

In this study, the levels of kappa opioid receptor (kOR) mRNA were determined using in situ hybridization following two types of stress (i.p. injection of hypertonic saline or novelty). In addition, we examined the possibility that estrogen or androgen would modify kOR mRNA. Gonadectomized male rats treated with estrogen or dihydrotestosterone were sacrificed 45 min after spending 15 min in a novel open field, or 60 min following hypertonic saline injection. Two-way ANOVA revealed that estrogen and novelty increased the levels of kOR mRNA in the ventral zone of the medial parvocellular part of the paraventricular nucleus (PVN), but not in the lateral parvocellular part of the PVN, claustrum, nucleus accumbens or the nucleus of the lateral olfactory tract. Furthermore, novelty increased kOR mRNA in gonadectomized (GDX) and GDX rats treated with dihydrotestosterone (DHTP), but not in sham-operated or estrogen-treated animals. Taken together, these data indicate that kOR mRNA levels are under estrogenic control and up-regulated in a stressor specific fashion.     

Differential effects of lesions in the amygdala, periamygdaloid cortex, and stria terminalis on aggressive behaviors in rats.

In 3 experiments, with a total of 113 male albino Sprague-Dawley rats, it was found that small lesions in the periamygdaloid cortex, cortical amygdaloid nucleus, or bed nuclei of the stria terminalis reduced or eliminated attacks and signs of dominance in fights which were generated by isolated housing and the omission of food reward. The same lesions had little or no effect on pain-induced or reflexive "fighting" or on mouse-killing. Small lesions in the lateral or central amygdaloid nuclei significantly inhibited pain-induced "aggression," but did not modify attack behavior or dominance in fights that occurred in situations not involving painful stimulation. These lesions also did not alter mouse-killing behavior. Results suggest that the periamygdaloid cortex and cortical amygdaloid nucleus, as well as the stria terminalis, may be part of a neural system which influences intraspecies aggression in male rats. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in NMDA receptor antagonist-induced locomotor activity and [3H]MK-801 binding sites in short-sleep and long-sleep mice

Short-Sleep (SS) and Long-Sleep (LS) mice differ in initial sensitivity to ethanol. Ethanol acts as an antagonist at N-methyl D-aspartate receptors (NMDARs). Therefore, we tested whether SS and LS mice also differ in initial sensitivity to NMDAR antagonists. Systemic injection (intraperitoneal) of either the noncompetitive NMDAR antagonist MK-801 (dizocilpine) or the competitive NMDAR antagonist 2-carboxypiperazin-4-yl-propyl-1-phosphonic acid (CPP) produced similar results. At lower drug doses, SS mice showed greater locomotor activation than LS mice; and at higher doses, SS mice continued to be activated whereas LS mice became sedated. Brain levels of [3H]MK-801 were 40% higher in SS, compared with LS, mice. However, blood levels of [3H]MK-801 and [3H]CPP and brain levels of [3H]CPP were similar in the two lines. NMDARs were measured using quantitative autoradiographic analysis of in vitro [3H]MK-801 binding to SS and LS mouse brains. Significantly higher (20 to 30%) receptor densities were observed in the hippocampus and cerebral cortex of SS mice. Our results support the hypothesis that SS and LS mice differ in initial sensitivity to NMDAR antagonists and suggest that the line differences in the dose-response relationships for MK-801- and CPP-induced locomotor activity are qualitatively similar to those reported for ethanol. Differences in pharmacokinetics and number of NMDARs may contribute to, but are unlikely to entirely account for, the differential behavioral responsiveness of SS and LS mice to MK-801 and CPP.     

Influences of deviations of thyroid functions on the effects of MAOI in rats--changes of 5-HT, 5-HIAA and norepinephrine contents and tyramine uptake by the brain and fluctuation of the rectal temperature]

The drug 6-hydroxydopamine (6-OHDA) has been reported to reduce hypothalamic norepinephrine (NE) content after administration into the lateral ventricle without altering the dopamine content of tubero-infundibular neurons. Serum prolactin levels in male rats injected with 2 X 250 mug 6-OHDA were significantly higher than in untreated control rats. Intraventricular injection of male rats with artificial cerebrospinal fluid resulted in elevated mean prolactin levels similar to those observed in 6-OHDA-treated animals. Further experimentation on animals decapitated at different times after removal from the animal quarters, indicates that prolcatin levels in 6-OHDA-treated rats are continuously elevated whereas they rise from basal levels to extremely high levels in CSF-treated rats, thus resulting in similar mean values. The CSF-treated controls ate hypersensitive to the stress of being removed from their normal environment. Such an effect was not observed in 6-OHDA-treated nor in untreated, and thus stress-inexperienced rats. In a long term study, serum prolactin and luteinizing hormone (LH) levels were followed over a period of 71 days after 6-OHDA treatment. Prolactin levels increased within one day after treatment and stayed at a high level for 15 days. Subnormal prolactin values were measured 37 days after 6-OHDA treatment. Serum LH levels were below normal 3 h and one day and were increased 37 and 71 days after 6-OHDA treatment. These results suggest that NE is important in the transmission of stressful stimuli to hypothalamic prolactin regulating centers. They further suggest functional recovery of LH and prolactin regulating mechanisms after 6-OHDA treatment.     

A longitudinal analysis of maternal aggression in Rockland-Swiss albino mice

Female Rockland-Swiss albino mice were treated for aggression during 6 successive pregnancies and lactation periods or until they ceased to re-mate. Fighting behavior was limited only to the lactation phase of each reproductive cycle. Although most animals exhibited fighting during every lactation period they completed, some exhibited fighting in some lactation periods but not in others. The intensity of aggression, as measured by the time spent fighting, was highest during the beginning of each lactation period and declined by the end of each period. Moreover, the intensity of aggression increased across the first 3 lactation periods and then declined on later lactation periods to a point below initial levels. Finally, the fighting behavior exhibited by multiparous animals was not due simply to previous fighting experience in that some multiparous mice exhibited postpartum aggression on the 6th lactation period in the absence of fighting experience during earlier lactation periods.