Behavioral effects of hashish in mice

The acute and subchronic effects of hashish extract (20mg ⁹-THC/kg) on the behavior of male mice encountering a control partner was studied by ethological methods. A single administration of the extract resulted in general sedation, suppressing all the individual and social activities with the exception of some submissive elements. The locomotive and the overall activity of drugged males was drastically reduced and immobility occurred frequently. After four applications, tolerance to the sedative effects had developed and behavioral drug effects were recognizable. Drugged males showed an increase in nonsocial activities as well as in submissive behavior and flight, whereas social investigation was less frequent. Sexual and aggressive behavior was not significantly affected by the drug and immobility no longer occurred.In spite of behavioral changes after a single or repeated drug treatment, drugged males became dominant in about half the experiments. The nest-building behavior of males was disturbed in the same way after one or four drug applications. Drugged males generally refrained from carrying and working up the nesting material.The acute behavioral effects of hashish extract are compared to those described in previous papers and the difference between acute and subchronic drug effects is discussed.     

Behavioral effects of hashish in mice

Within groups of three adult male mice the acute and subchronic effects of hashish extract (20 mg ⁹ - THC/kg) on social dominance, food dominance, and sexual interactions with a female were investigated. An initial drug treatment of only the dominant male weakened his social position, but dominance was regained after treatment 2 or 3. In contrast, a persistent change in dominance was found when only the male which was dominant in the feeding test was treated with the extract. Simultaneous drug treatment of all three males did not affect the social dominance relationship but resulted in a reversible change in food dominance. The original feeding order was reestablished after drug treatment 3. Upon meeting an estrous female, no male of the group was distinctly dominant in mating. After treatment 1 was given to all members of the group, all types of behavior were impaired and total activity was significantly reduced. After treatment 2, animals showed tolerance to the sedative effects, and after treatment 3, sexual behavior was even more frequent in drugged animals than in controls. The results are discussed in relation to a possible dependence of behavioral drug effects and tolerance development on the experimental situation. Present Address: I.C.I.P.E. Research Centre, PO Box 30772, Nairobi, Kenya     

Hashish extract impairs retention of defeat-induced submissive behavior in mice

The effects of hashish extract on adaptive behavior of male mice were studied in a paradigm which allows the investigation of learning mechanisms in a social context. Mice of the C3H strain, which were not submissive in a confrontation with a nonaggressive DBA mouse on day 1, were defeated on day 2 over 3 min by aggressive, isolated DBA mice, and showed conditioned submissive behavior upon mere contact with a nonaggressive DBA mouse on day 3. A hashish extract containing 38.6–39.4% ⁹-tetrahydrocannabinol ( ⁹-THC), 11.6–12.0% cannabinol and 47.7–48.5% cannabidiol was administered orally in all experiments. Hashish extract given 90 min before defeat on day 2, in dosages corresponding to 1, 5, and 10 mg ⁹-THC/kg, impaired retention of defensive upright, defensive sideways and immobility on day 3 (experiment 1). Experiment 2 showed that the drug (5, and 10 mg ⁹-THC/kg) had no antinociceptive potency in mice and did not modify defeat-induced analgesia. Experiment 3, with drug (5 mg ⁹-THC/kg) or solvent administration on day 2 and day 3, showed that the retention deficit was neither due to state-dependent learning, nor to impaired retrieval. It is suggested that hashish extract administered before learning may interfere with memory processing.     

Opposite effects of agonist and inverse agonist ligands of benzodiazepine receptor on self-defensive and submissive postures in the rat

The effects of benzodiazepine receptor ligands on different types of defensive behaviours were examined in intruder male rats confronted with offensive residents. Chronic administration, via a subcutaneous silastic pellet, of a full agonist (diazepam) for 15 days increased self-defensive postures as well as social and non-social behaviour whereas submissive postures and flight were reduced. Acute administration of a partial agonist (ZK 91296) resulted in a similar increase in self-defensive postures and a decrease of submissive and non-social elements. Acute administration of a partial inverse agonist (FG 7142) reduced defensive postures and social behaviour whereas submissive postures were increased. These results show that activation of benzodiazepine receptors by full or partial agonists increased self-defensive responses to attacks by a conspecific, while decreasing submissive postures. On the contrary, inverse activation of these receptors by an inverse agonist increased submissive postures while decreasing self-defensive responses. These data suggest that benzodiazepine receptors are involved in the control of the animal's strategy to respond to an attack of another rat.     

Opposite effects of pentylenetetrazol on self-defensive and submissive postures in the rat

In a previous work, using the resident-intruder situation, we have shown that a benzodiazepine inverse agonist could exert a fear-promoting effect, in decreasing self-defensive behaviours while increasing submissive postures. To further test this hypothesis, the effects of pentylenetetrazol on different forms of defensive behaviour were examined in male intruder rats confronted with offensive residents. Administration of pentylenetetrazol (10 and 20 mg/kg, IP) increased submissive postures such as immobility and on-the-back, but reduced self-defensive postures. Other active behaviours were not reduced, thus excluding a non-specific behavioural suppression. These results suggest that self-defensive and submissive behaviours can be dissociated and that anxiogenic compounds are more likely to increase submissive behaviours than self-defensive ones.     

Intense cocaine self-administration after episodic social defeat stress,but not after aggressive behavior: dissociation from corticosterone activation

Rationale:

An intense stress response characterizes both the dominant and submissive individuals during an aggressive confrontation, and these stress responses have enduring neural and behavioral consequences.

Objectives:

In spite of similar glucocorticoid and corticolimbic dopamine activation, dominant and defeated individuals appear to diverge in terms of their drug taking. Do rats that are intermittently subjected to defeat stress become more sensitized to cocaine taking relative to rats that engage in aggressive bouts?

Methods:

Separate groups of male Long-Evans rats were investigated after an initial 10-day period with four brief episodes of social defeat (intruders) or aggressive behavior (residents): (1) the corticosterone responses to the very first and the last confrontations were measured; (2) the locomotor response to an amphetamine (1 mg/kg) challenge 10 days after the last stress exposure served as an index of behavioral sensitization; (3) intravenous self-administration sessions assessed the reinforcing effects of 0.75 mg/kg/infusion cocaine when available after every fifth response (fixed ratio), when delivered after completing progressively more demanding response requirements (progressive ratio; 0.3 mg/kg/infusion), and when available during a 24-h binge of continuous access (0.3 mg/kg/infusion).

Results:

Both social defeat of the intruder rat and attack behavior by the resident rat rapidly increased plasma levels of corticosterone after the first and last aggressive confrontation, indicating no habituation to these types of stress. Intermittent social defeat engenders a sensitized locomotor response to a 1 mg/kg amphetamine challenge and increases cocaine self-administration as indicated by more behavioral effort to obtain cocaine infusions and by accumulating more cocaine during 24 h of continuous access (binge). By contrast, experiences with aggressive behavior do not impact on the motorically activating and reinforcing effects of stimulant administrations.

Conclusions:

The closely similar corticosterone activation in dominant and subordinate rats, followed by divergent patterns of cocaine self-administration indicates that different forms of social stress have dissociable effects on cocaine taking.

     

Testosterone modulates the effects of ethanol on male mouse aggression

In a series of three experiments, we evaluated the degree to which the effects of acutely administered ethanol on aggressive behavior of male CFW mice toward a male intruder interact with, and depend on, androgen levels. In the first experiment, mice were tested at 15 min after 0, 0.1, 0.3, 1.0, 1.7, or 3.0 g/kg of ethanol PO. The highest dose (3.0 g/kg) significantly suppressed aggression by the male residents. In the second experiment, aggressive behavior was suppressed from 5 to 60 min after 3.0 g/kg ethanol administration PO. The third experiment evaluated the role of testosterone in these effects in another set of male mice that were castrated and then implanted with a 7.5-mm or 2.5-mm silastic capsule of testosterone (T) or a silastic capsule containing cholesterol as a control. The castrated mice with 2.5-mm T capsules or cholesterol capsules had lower baseline levels of aggression than intact mice or castrated males with 7.5-mm T capsules, but they demonstrated an alcohol dose-response pattern similar to that of the intact males. The castrated males with 7.5-mm T capsules had a different dose-response curve than the other males. Doses of 1.0 and 1.7 g/kg ethanol PO significantly enhanced aggression; 5.6 g/kg was required to suppress aggression. Ethanol effects on aggressive behavior did not require T or changes in T level, but T levels altered behavioral sensitivity to ethanol.     

Influence of hashish extract on the social behaviour of encountering male baboons (Papio c. anubis)

The effects of hashish extract (2 mg Δ⁹-THC/kg)on the social behaviour of encountering male baboons were tested by ethological methods. In the “approaching” male the drug reduced “approach” and the aggressive elements “hit-ground”, “brows-back” and “attack” but increased the frequency of “retreat”. Social interactions were generally diminished. In the “retreating” male friendly social interactions as “lipsmack” and “touch-back/handle-genitals” were suppressed but thethreatening elements “open-mouth” and “tooth-grind” were stimulated. “Retreat” was additionally more frequent. Non-social activities and locomotion were not affected in either of the males. Treating both subjects with hashish resulted in a reduction of “lipsmack”, “approach”, “fight” and “chase” in the approaching and “lipsmack”, “touch-back/handle-genitals”, “chase”, “retreat” and “flee” in the retreating male. Social activities were generally reduced in both animals. Comparing the behavioural effects of hashish in male baboons to those described in other non-human primates, in rodents but also in man revealed analogous effects in all species. The drug generally impaired social interactions, induced social withdrawal and led to social isolation of the drugged subject.     

“Anxiolytic” and “anxiogenic” benzodiazepines and β-carbolines: effects on aggressive and social behavior in rats and squirrel monkeys

Ethopharmacological studies on the behavior of socially housed rats and squirrel monkeys were conducted to explore the role of the benzodiazepine GABA_A-coupled ionophore receptor complex in aggressive and social interactions. Benzodiazepine receptor (BZR) antagonists, ZK 93426 (1–10 mg/kg) and flumazenil (3–10 mg/kg), the partial agonist, ZK 91296 (1–10 mg/kg) and the partial inverse agonists RO 15-4513 (0.3–10 mg/kg), were administered to (1) squirrel monkeys prior to 1 h focal observations within established social groups or to (2) resident male rats before confrontations with a naive male intruder in their home cage for 5 min. Aggression was modified in a similar manner in both species, although squirrel monkeys were more sensitive to BZR challenges. Specifically, resident male rats showed dose dependent reductions in attack bites directed at intruder males that were significant at the highest dose of ZK 93426 (10 mg/kg). In squirrel monkeys, ZK 93426 (3 and 10 mg/kg) reduced aggressive grasps, threats and displays, as well as reducing the duration of being the target of aggression from untreated group members (1–10 mg/kg). The BZR partial agonist, ZK 91296 and the antagonist, flumazenil produced few effects on social behavior, low and high intensity aggression and motor activity in both species. Flumazenil (10–30 mg/kg) and ZK 91296 (10 mg/kg), but not ZK 93426, produced significant increases in foraging and feeding behaviors in squirrel monkeys. The hyperphagic effects of ZK 91296 and flumazenil, that are typical of BZR agonists compounds, were not observed in rats. Similarly, the inverse agonist-like reductions in social interactions produced by ZK 93426 (3–10 mg/kg) were observed only in squirrel monkeys. The partial inverse agonist Ro 15-4513 reduced aggression in rats, but low doses (1 mg/kg) produced tremors or seizures in 80% of the monkeys tested. Decreases in aggressive and social behaviors are often interpreted to reflect anxiogenic drug properties, whereas increased feeding has been associated with anxiolytic actions. The concurrent emergence of these apparent opposites suggests independent actions on social and alimentary functions.     

A possible olfactory component in the effects of diazepam on social behavior of mice

The means by which diazepam alters the social behavior of male LAC mice was investigated by analyzing 6-min dyadic social encounters between untreated, individually housed resident males and experimentally manipulated, group-housed intruders. Experiment 1 showed that at 24h and particularly 14days after access to 0.125 mM diazepam solution, drugged intruders were attacked more when placed into a resident's home cage than were intruders receiving vehicle. After 24h, but not 14 days of treatment, drugged intruders performed fewer elements of static flight. However, on both occasions they showed proportionally less flight behavior relative to the amount of aggression residents directed towards them. In experiment 2, intruders marked with mouse urine taken from donors which had ingested the 0.125 mM diazepam solution for 24h were attacked considerably more by residents than were intruders marked with water or normal mouse urine. Urine samples taken after 14 days of drug treatment evoked additional increases in sexual and investigatory elements in unmarked residents. The results show that, in pairs of mice, the rise in aggression associated with sustained diazepam treatment, unlike the changes in flight, arises indirectly and probably through a drug-induced change in the olfactory properties of mouse urine.     

Alcohol and “bursts” of aggressive behavior: ethological analysis of individual differences in rats

A quantitative ethological analysis of rodent aggression was performed in order to characterize the aggression-heightening effects of alcohol in certain individuals. In dyadic confrontations, a resident rat pursues, threatens and attacks an intruder, who reacts with defensive, flight and submissive behaviors. The behavioral data from five series of experiments conducted from 1984 through 1989 were subjected to a lag sequential analysis that identified highly predictable sequences of aggressive behavior, and to interval analysis that delineated a burst pattern of aggressive behavior. These analyses revealed a distinct behavioral sequence of pursuit sideways threat attack bite aggressive posture that occurs in bursts with an inter-event interval of less than 6.6 s. In the total population, alcohol heightened attack behavior at low acute doses (0.1, 0.3, 1.0 g/kg) in 47% of the animals (n=44), suppressed reliably attack behavior in another 25% (0.1–3.0 g/kg;n=23) and had unreliable effects in the remaining 28% (n=24). The peak enhancement of aggressive behavior was seen over more than a log cycle of alcohol doses (0.1, 0.3 or 1.0 g/kg) in different individuals. In an additional group of rats (n=20), individuals were identified according to whether or not acute low alcohol doses enhanced or suppressed the frequency of attack bites. In the subgroup of five rats who doubled their attack frequency upon acute alcohol challenge, this aggression-heightening effect was confirmed on repeated occasions. The aggression-heightening effects of alcohol were seen during the high-rate interactions in the initial phase of the confrontation and particularly during the lower level of fighting later on. Regardless of alcohol dose and subgroup, the highly predictable sequence of pursuit sideways threat attack bite aggressive posture remained intact as long as the individual was able to fight. The present analysis identifies those individuals in whom low alcohol doses increase the frequency of attack behavior, the number of aggressive elements in bursts and particularly the time in burst. Alcohol produces these changes without altering the latency to initiate aggressive behavior, the rate of aggressive behavior within a burst or the number of bursts in an encounter. Alcohol may lengthen aggressive bursts by preventing termination of longer aggressive sequences rather than by altering the initiation of this behavior.We dedicate this paper to our friend Dr. Milos Krsiak, Professor of Pharmacology, Charles University, Prague, Czechoslovakia     

Comparison of the effects of benzodiazepine and non-benzodiazepine anxiolytics on agonistic behavior in male mice]

The present study investigated whether there is any difference between the effects of benzodiazepine and non-benzodiazepine anxiolytics on agonistic behavior in male mice, using an ethopharmacological technique. Agonistic behavior was evoked using a resident-intruder paradigm. The effects of four doses of the following drugs were assessed in either resident or intruder mice: diazepam (vehicle, 1, 2.5 and 5 mg/kg, p.o.) and tandospirone (vehicle, 2.5, 5 and 10 mg/kg, p.o.). Residents and intruders were drugged on alternate test days, and all animals received different sequences of each of the drug conditions according to a random schedule. The injection-test interval was 30 min. When a resident mice were treated with either diazepam or tandospirone, the frequency of attack bite was suppressed significantly in a dose-dependent manner. When intruder mice were treated with diazepam, attack bites by untreated residents were significantly increased, whereas tandospirone was ineffective. Although diazepam caused a significant decrease in both locomotion and rearing, tandospirone did not cause motor dysfunction. These evidence indicate that tandospirone, a 5-HT1A receptor agonist, has different pharmacological properties from diazepam.     

Pharmaco-ethological analysis of agonistic behavior between resident and intruder mice: effects of psychotropic drugs

The present study was conducted to investigate the effects of psychotropic drugs on agonistic behavior between resident and intruder mice. The effects of four doses of the following drugs were assessed in either resident or group-housed intruder mice: chlordiazepoxide (0, 5, 10 and 20 mg/kg, i.p.), haloperidol (0, 0.25, 0.50 and 0.75 mg/kg, i.p.) and imipramine (0, 5, 10 and 20 mg/kg, i.p.). Residents and intruders were drugged on alternate test days, and all animals received different sequences of each of the drug conditions according to a random schedule. The injection-test interval was 30 min. When resident mice were treated with chlordiazepoxide the resident's aggressive episodes (sideways posture, attack bite, tail rattle) were significantly suppressed. Both haloperidol and imipramine also showed a similar suppressive effect on the resident's aggressive episodes, but haloperidol significantly suppressed locomotor activity at all doses. When intruder mice were treated with chlordiazepoxide, attack bites by untreated residents were significantly increased in a dose-dependent manner, and the frequency of defensive upright posture displayed by intruder animals were significantly decreased. Haloperidol and imipramine did not alter resident's behavior and intruder's upright posture when intruders were drugged. The results suggest that chlordiazepoxide has specific effects on both the hostility of the resident and the anxiety of the intruder, differing from haloperidol and imipramine.     

Anxiolytic and antidepressant-like effects of Melissa officinalis (lemon balm) extract in rats: Influence of administration and gender

Objective:

To analyse the behavioral effects of Melissa officinalis extract in rats following acute or subacute treatment.

Materials and Methods:

The behavioral effects of an acute or subacute (10-day course) orally administered M. officinalis (MO; 0, 30, 100 or 300 mg/kg) ethanol extract were evaluated in male and female Wistar rats in elevated plus-maze (EPM), forced swimming (FS) and open field (OF) tests. The effects of diazepam (DZP; 1 mg/kg) and fluoxetine (FXT; 10 mg/kg) were also assessed.

Results:

In the EPM test, the percentage of open arm entries and open arm times of both males and females given the subacute M. officinalis ethanol extract were significantly higher than those of the vehicle-treated animals but were at levels similar to those observed in the DZP group, regardless of the treatment length. In the FS test, immobility duration was significantly lower in both males and females treated with the plant extract when compared to vehicle-treated counterparts. A 10-day treatment with FXT induced the same antidepressant response, regardless of gender, and was more effective than the M. officinalis extract. Male and female rats demonstrated distinct gender profiles, and treatment × gender interactions were observed. Locomotion in the EPM and OF tests was not significantly altered by treatments.

Conclusion:

The potential psychoactive properties of M. officinalis may provide a unique pharmacological alternative for certain psychiatric disorders; however, the efficacy appears to be dependent on both gender and administration length.KEY WORDS: Anxiety, depression, gender, locomotion, Melissa officinalis     

Sex-dimorphic psychomotor activation after perinatal exposure to (−)-Δ9-tetrahydrocannabinol. An ontogenic study in wistar rats

The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to ⁹-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone. These results confirm our previous finding of a sex-dimorphic behavioral response to perinatal exposure to hashish extracts, and they suggest a role of THC-induced PA activation in the mediation of these actions.     

Alcohol,anxiolytics and social stress in rats

The main objective was to compare the anxiolytic-like profiles of alcohol, diazepam and gepirone along the stress intensity gradient which characterizes consecutive phases of a social confrontation. The acute social stress situation consisted of initially placing the experimental rat as an intruder into the homecage of a resident while the resident was not present, termed the anticipatory phase, thereafter permitting brief physical agonistic interactions with the re-introduced resident until the intruder was forced into a submissive supine posture and emitted ultrasonic vocalizations (USV), and eventually exposing the intruder to the resident's threats for 1 h, while being shielded from potential injurious attacks. The hyperthermia, measured via telemetry, in the anticipatory phase prior to defeat and in reaction to threats, was decreased by alcohol, gepirone and diazepam; alcohol and gepirone were also effective in attenuating anticipatory tachycardia. Alcohol, like gepirone and diazepam, also decreased defensive responses and ultrasonic vocalizations in the anticipatory phase of the confrontation, but none of these drugs affected defensive reactions to threats which immediately followed defeat. Gepirone had no systematic sedative effects throughout the confrontation; infact, it dose-dependently reduced the stress-induced suppression of locomotor activity during the anticipatory phase. In contrast, at higher doses, alcohol as well as diazepam had marked sedative effects as evidenced by several behavioral parameters (i.e. lie, crouch, walk). The anxiolytic-like profile of hyperthermia, tachycardia, USV and defensive behavior in the anticipatory phase of the confrontation by alcohol, gepirone and diazepam contrasted with the lack thereof during the more intense reactive phase. This differential pattern of effects appears to be relevant to the clinical distinctions between anticipatory anxiety and other affective disturbances.     

Acute and residual effects of alcohol and marijuana,alone and in combination,on mood and performance

The duration of behavioral impairment after marijuana smoking remains a matter of some debate. Alcohol and marijuana are frequently used together, but there has been little study of the effects of this drug combination on mood and behavior the day after use. The present study was designed to address these issues. Fourteen male and female subjects were each studied under four conditions: alcohol alone, marijuana alone, alcohol and marijuana in combination, and no active treatment. Mood and performance assessments were made during acute intoxication and twice the following day (morning and mid-afternoon). Acutely, each drug alone produced moderate levels of subjective intoxication and some degree of behavioral impairment. The drug combination produced the greatest level of impairment on most tasks and strong overall subjective ratings. There were few significant interactions between the two drugs, indicating that their effects tended to be additive. Only weak evidence was obtained for subjective or behavioral effects the day after active drug treatments, although consistent time-of-day effects (morning versus afternoon) were observed on several subjective and behavioral measures. In sum, this study provided little evidence that moderate doses of alcohol and marijuana, consumed either alone or in combination, produce behavioral or subjective impairment the following day.     

Social model of depression in mice of C57BL/6J strain

Long experience of defeat in daily social intermale confrontations and permanent living with aggressive males under sensory contact conditions [Kudryavtseva (8)] has been shown to produce changes in the patterns of submissive behavior of male mice of C57BL/6J strain. The submissive males after 20 defeats demonstrated passive defense postures instead of active defense and withdrawal which they had displayed in first encounters. Moreover, new immobile postures appeared, which were very rare in the first confrontations. Submissive animals displayed a decrease of ambulation in the open-field test and increase the immobility time in the Porsolt's test. Chronic treatment with imipramine prevented the increase of "depressiveness" estimated by means of the Porsolt's test. There was a loss of weight and some disturbances in gastrointestinal functions. The data are discussed in terms of the development of depression in submissive male C57BL/6J mice as a result of chronic unavoidable social stress.     

Antiaggressive activity of central oxytocin in male rats

Rationale

A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans. However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents.

Objective

Our primary goal was to examine the putative serenic effect of oxytocin in a feral strain (wild type Groningen, WTG) of rats that generally show a much broader variation and higher levels of intermale aggression than commonly used laboratory strains of rats.

Methods

Resident animals were intracerebroventricularly (icv) administered with different doses of synthetic oxytocin and oxytocin receptor antagonist, alone and in combination, in order to manipulate brain oxytocin functioning and to assess their behavioral response to an intruder.

Results

Our data clearly demonstrate that acute icv administered oxytocin produces dose-dependent and receptor-selective changes in social behavior, reducing aggression and potentiating social exploration. These antiaggressive effects are stronger in the more offensive rats. On the other hand, administration of an oxytocin receptor antagonist tends to increase (nonsignificantly) aggression only in low–medium aggressive animals.

Conclusions

These results suggest that transiently enhancing brain oxytocin function has potent antiaggressive effects, whereas its attenuation tends to enhance aggressiveness. In addition, a possible inverse relationship between trait aggression and endogenous oxytocinergic signaling is revealed. Overall, this study emphasizes the importance of brain oxytocinergic signaling for regulating intermale offensive aggression. This study supports the suggestion that oxytocin receptor agonists could clinically be useful for curbing heightened aggression seen in a range of neuropsychiatric disorders like antisocial personality disorder, autism, and addiction.     

Sex differences in novelty- and psychostimulant-induced behaviors of C57BL/6 mice

Rationale

Women are more sensitive than men to psychostimulants and progress from initial use to drug addiction more quickly. The mouse has been an under-utilized model to study sex differences in psychostimulant action. Mice could serve as an ideal genetically tractable model for mechanistic studies into sex and hormone effects on psychostimulant behavior.

Objectives

The objective of this study was to characterize psychostimulant effects in male and female mice with a combination of automated data collection and behavioral observation.

Methods

Male and female C57BL/6 mice (Charles River) were given a single dose or sequential ascending binge doses of d-amphetamine (AMPH) or cocaine (COC). Behavior was assessed in open field chambers using both automated photobeam interruptions and behavioral observations. Brain psychostimulant concentrations were determined at the time of maximum behavioral stimulation.

Results

Psychostimulants induced behavioral activation in mice including both increased locomotion as detected with an automated system and a sequence of behaviors progressing from stereotyped sniffing at low doses to patterned locomotion and rearing at high doses. Females exhibited more patterned locomotion and a shift towards higher behavior scores after either psychostimulant despite having lower AMPH and equivalent COC brain levels as males.

Conclusions

Female C57BL/6 mice exhibit enhanced psychostimulant-induced behavior compared to males, similar to reports in rats. The combination of automated behavioral measures and behavioral observation was essential for verifying the existence of these differences. These results indicate the importance of testing both sexes when characterizing genetically manipulated mice to control for potential sex-specific effects.