首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
GABA‐A receptor is a transmembrane hetero‐oligomeric protein which consists of five subunits, the combination of which confers unique pharmacological properties to the receptor. It is well‐known that the GABAergic system is involved in the modulation of aggression. However, the role of α5/GABA‐A receptors has not been explored. In this study, we examined the effect of L‐655,708 (0.625‐5 mg/kg), a selective ligand for the benzodiazepine site of GABA‐A receptors which contain the α5 subunit, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to an anosmic “standard opponent” 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. L‐655,708 (5 mg/kg) exhibited an ethopharmacological profile characterized by a marked reduction of the time spent in offensive behavior (threat and attack) without affecting immobility, accompanied by a significant increase of avoidance/flee and nonsocial exploration behaviors, suggesting that the antiaggressive effect of the drug is unselective. Overall, this behavioral profile might indicate the existence of an anxiogenic‐like activity of L‐655,708 in mice. Aggr. Behav. 30:319–325, 2004. © 2004 Wiley‐Liss, Inc.  相似文献   

2.
In the present study the effects of a wide range of doses of the dopamine release inhibitor CGS 10746B were evaluated in spontaneous activity and in aggressive behaviour using the paradigm of isolation‐induced aggression. The two higher doses (8 and 16 mg/kg) produced a decrease in spontaneous motor activity. Antiaggressive effects were observed after administration of doses from 4 mg/kg upwards. At this dose, CGS 10746B diminished threat and attack, and although an increase in immobility was observed, no impairment of other motor behaviours was presented. With higher doses, aggression was practically abolished but with a concomitant effect on many other behaviours. When animals were separated depending on their latency of attack, those that showed a long attack latency (LAL) presented a stronger response to 4 mg/kg than those that had a short attack latency (SAL), which were not affected in their aggression by this dose. We can conclude that presynaptic dopamine function is necessary for the normal expression of aggressive behaviours, since CGS 10746B reduces aggression at doses that do not affect spontaneous motor activity. Aggr. Behav. 27:382–390, 2001. © 2001 Wiley‐Liss, Inc.  相似文献   

3.
The aim of this work was to test the antiaggressive effects of lorazepam and to determine whether these effects were mediated by benzodiazepine receptors. In a first experiment, male mice were injected with lorazepam in a range of low doses (0.05, 0.1, 0.2, and 0.6 mg/kg) or saline solution. In a second experiment, 1 mg/kg of Ro 15‐1788, a benzodiazepine receptor antagonist, and a saline solution were injected before the behavioral test. Results showed that 0.6 mg/kg of lorazepam was the only dose that decreased the total duration of threat (P < .01) and social investigation (P < .05) and that 1 mg/kg of Ro 15‐1788 had no effects. In the third experiment, animals received two injections: 0.6 mg/kg of lorazepam plus 1 mg/kg of Ro 15‐1788, 0.6 mg/kg of lorazepam plus saline solution, or saline solution plus saline solution. Those treated with lorazepam and saline solution spent less time digging (P < .001), threatening (P < .001), and attacking (P < .05) and more time avoiding the opponent (P < .01) or being immobile (P < .001) than the controls. Ro 15‐1788 was successful in completely antagonizing the behavior modulated by lorazepam. Aggr. Behav. 28:248–256, 2002. © 2002 Wiley‐Liss, Inc.  相似文献   

4.
Recent studies suggest that acute administration of 3,4‐methylenedioxymethamphetamine (MDMA), an amphetamine derivative popularly known as “ecstasy,” produces an antiaggressive effect in male mice. However, there is no evidence with respect to the development of tolerance or sensitization after its subchronic or intermittent administration. In this study, we examined the action of low to moderate doses of MDMA (1.25, 2.5 and 5 mg/kg, i.p), administered acutely, subchronically (for 7 days) or intermittently, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic “standard opponents” 30 minutes after the drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Acute treatment with MDMA provoked a significant reduction of aggressive behaviors, without altering immobility. However, this action was only selective at 1.25 mg/kg. With the intermediate (2.5 mg/kg) and the highest doses (5 mg/kg) of the drug, it was observed a significant decrease of offensive behaviors, accompanied by an increase of exploration from a distance, avoidance/flee and defense/submission behaviors. This ethopharmacological profile could indicate the existence of an anxiogenic‐like effect of MDMA. The overall picture of the effects of MDMA was very similar in the acutely, intermittently and daily treated animals. No tolerance or sensitization to the actions of the drug was developed after its repeated or intermittent administration.  相似文献   

5.
The 5HT1A receptor agonist ipsapirone (10 mg/kg) suppressed shock-induced aggression in wild and domesticated rats but did not affect predatory aggression in either group of animals. Ipsapirone decreased neophobia and inhibited defensive reactions by wild rats towards man in the glove test. [3H]8-OH-DPAT binding, which labels 5HT1A receptors, was significantly increased in the hypothalamus of domesticated rats in comparison with wild counterparts, while 5HT1A density was unchanged in the frontal cortex in domesticated animals. In essence, the aggressive reactions contributing to the defensive behavior complex in wild rats appear to be regulated through 5HT1A receptors. © 1992 Wiley-Liss, Inc.  相似文献   

6.
Alpha-2 adrenoceptors (alpha(2)-ARs) are critically involved in regulating neurotransmitter release from sympathetic nerves and neurons and play an important role in the regulation of awareness, arousal and vigilance. In our recent study, dexmedetomidine, a full alpha(2)-AR agonist, produced antiaggressive effects in the social conflict test in mice at doses that were twice smaller than those producing sedation. The aim of this study was to ascertain antiaggressive effect of a novel drug naphthylmedetomidine, with a more selective alpha(2)-AR activity. Behavioral effects of naphthylmedetomidine (150-1200 microg/kg i.p.) were studied in the activity cage and in the social conflict tests in mice. Naphthylmedetomidine dose dependently decreased aggressive behavior during social conflict in aggressive mice with significant reduction already at the lowest doses tested (150 microg/kg), whereas locomotion and social investigation were significantly decreased only after four times bigger dose of naphthylmedetomidine (600 microg/kg) in aggressive mice. Naphthylmedetomidine had no effect on aggression in nonaggressive mice. Naphthylmedetomidine reduced locomotion in the activity cage significantly only at the highest doses tested (600 and 1200 microg/kg), and this effect was only partially reversed by administration of high doses of an alpha-2 antagonist atipamezole (3 and 10 mg/kg). In nonaggressive mice, the difference between the dose reducing dominant social behavior (social investigation) and locomotion (150 and 300 microg/kg, respectively) was smaller than in aggressive mice. In conclusion, naphthylmedetomidine showed a very strong and selective antiaggressive effect in aggressive mice, which was devoid of locomotion-inhibiting/sedative effect. This study suggests that naphthylmedetomidine may have clinical potential as antiaggressive drug.  相似文献   

7.

Treatment of rats with the potent antiaggressive compound eltoprazine hydrochloride (1.0 & 2.0 mg/kg) slowed both predatory attack and killing of frogs. These results demonstrate a specific predation-inhibiting action of the drug which is not obscured by the elements of conspecific aggression seen during muricide. Unlike the closely related compound fluprazine, eltoprazine increased both attack and kill latencies implying that the effects of the two drugs on predation are mediated by at least somewhat distinct drug actions. It is further suggested that eltoprazine may be more specifically antiaggressive in its actions than related phenylpiperazine compounds.

  相似文献   

8.
Omega‐3 supplementation has been found to reduce externalizing behavior in children. Reciprocal models of parent‐child behavior suggest that improving child behavior could lead to improvements in parent behavior, however no study has examined whether omega‐3 supplementation in children could reduce intimate partner violence or child maltreatment by their adult caregivers. In this randomized, double‐blind, placebo‐controlled, stratified, parallel group trial, a community sample of children were randomized to receive either a fruit drink containing 1 gm of omega‐3 fats (Smartfish Recharge; Omega‐3 group, n = 100) or the same fruit drink without omega‐3's (Placebo group, n = 100). Child participants, adult caregivers, and research staff were blinded to group assignment. Adult caregivers reported inter‐partner and child‐directed physical assault and psychological aggression at baseline, 6 months (end of treatment) and 12 months (6 months post‐treatment) using the Conflicts Tactics Scale. Caregivers of children in the omega‐3 group reported long‐term reductions in psychological aggression in a group × time interaction. Improvements in adult psychological aggression were correlated with improvements in child externalizing behavior scores. No differences were reported for child maltreatment. This study is the first to show that omega‐3 supplementation in children can reduce inter‐partner psychological aggression among adult caregivers not receiving supplements. Findings suggest that improving child behavior through omega‐3 supplementation could have long‐term benefits to the family system as a whole.
  相似文献   

9.
Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5‐HT)2C receptors and might also have agonist properties at other 5‐HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague–Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed‐ratio 5 schedule for food. Lorcaserin (0.178‐1.0 mg/kg) dose‐dependently increased lorcaserin‐lever responding. The 5‐HT2C receptor agonist mCPP and the 5‐HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin‐lever responding in seven of eight rats. The 5‐HT1A receptor agonist 8‐OH‐DPAT occasioned greater than 90% lorcaserin‐lever responding in four of seven rats. The 5‐HT2C receptor selective antagonist SB 242084 attenuated lorcaserin‐lever responding in all eight rats and the 5‐HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin‐lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5‐HT2C receptors, lorcaserin also has agonist properties at 5‐HT2A and 5‐HT1A receptors. Because some drugs with 5‐HT2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders.  相似文献   

10.
The GABAAR α4 subunit is highly expressed in the dentate gyrus region of the hippocampus at predominantly extra synaptic locations where, along with the GABAAR δ subunit, it forms GABAA receptors that mediate a tonic inhibitory current. The present study was designed to test hippocampus-dependent and hippocampus-independent learning and memory in GABAAR α4 subunit-deficient mice using trace and delay fear conditioning, respectively. Mice were of a mixed C57Bl/6J X 129S1/X1 genetic background from α4 heterozygous breeding pairs. The α4-knockout mice showed enhanced trace and contextual fear conditioning consistent with an enhancement of hippocampus-dependent learning and memory. These enhancements were sex-dependent, similar to previous studies in GABAAR δ knockout mice, but differences were present in both males and females. The convergent findings between α4 and δ knockout mice suggests that tonic inhibition mediated by α4βδ GABAA receptors negatively modulates learning and memory processes and provides further evidence that tonic inhibition makes important functional contributions to learning and behavior.  相似文献   

11.
Amisulpride is a substituted benzamide derivative that acts as a selective dopamine D2/D3 receptor antagonist. Although the anti‐aggressive properties of neuroleptic drugs are well known, the effects of amisulpride on agonistic interactions have not been explored, and there are no studies comparing acute and subchronic effects of this compound on aggression in rodents. In this study, we examined the action of amisulpride (5–25 mg/kg, i.p), administered acutely or subchronically for 10 days, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. After acute treatment, amisulpride (5–20 mg/kg) exhibited an ethopharmacological profile characterized by a marked decrease of offensive behaviors (threat and attack) without an impairment of motor activity. By contrast, the anti‐aggressive action of the highest dose used (25 mg/kg) was accompanied by a weak increase of immobility. Body care was also significantly enhanced after treatment with the drug (20 and 25 mg/kg), emphasizing the involvement of dopaminergic receptors in this behavior. After subchronic treatment, no tolerance to amisulpride anti‐aggressive activity was observed. Overall, this behavioral profile is similar to that observed by other atypical neuroleptics. Aggr. Behav. 25:225–232, 1999. © 1999 Wiley‐Liss, Inc.  相似文献   

12.
Brain-derived neurotrophic factor (BDNF) has been shown to promote synapse formation and maturation in neurons of many brain regions, including inhibitory synapses. In the cerebellum, the Golgi cell-granule cell GABAergic synaptic responses undergo developmental transition from slow-decaying to fast-decaying kinetics, which parallels a developmental increase of GABAA receptor α6 subunit expression in the cerebellar granule cells. In culture, BDNF accelerates the expression of GABAA receptor α6 subunit expression in granule cells. Here we examined synaptic GABAA response kinetics in BDNF transgenic mice. The mutant mouse, which carries a BDNF transgene driven by a β-actin promoter, overexpresses BDNF (two- to fivefold increase compared with wild types) in all brain regions. Recordings of the spontaneous GABAA responses indicate that the decay time constant of the GABAergic responses decreases during early postnatal development; this transition is accelerated in the BDNF transgenic mouse. The amplitude of the spontaneous GABAA responses was also larger in the transgenic mouse than in the wild-type mouse. However, the frequency of the spontaneous GABAA responses were not different between the two groups. Our results suggest that BDNF may modulate GABAergic synapse maturation in the cerebellum.  相似文献   

13.
This review outlines recent research on a subset of physiological responses in murine “victims” or aggression. In a typical resident-intruder paradigm, the detailed study of intruders has revealed that exposure to conspecific attack (and related stimuli) is associated with two forms of analgesia which appear to be integral components of the murine defensive repertoire. In response to intense/enduring attack, intruder mice display a profound, long-lasting and opioid-mediated analgesia. This reaction is highly correlated with defensive immobility and may function to reduce involuntary cues to further attack. In contrast, the inhibition of pain reactivity in mice tested immediately upon the display of defeat is less intense, shorter-lasting, non-opioid in nature and may function to facilitate active defenses such as escape. As this form of pain inhibition is also evident in intruders exposed to the scent of an aggressive male conspecific, a possible anticipatory defensive function linked to mechanisms of anxiety has been proposed. This hypothesis is supported by 1) the prevention of defeat analgesia by a range of antianxiety drugs (benzodiazepines, 5-hydroxytryptamine1A [5-HT1A] receptor agonists, and 5-HT3 receptor antagonists) and 2) the effects of social defeat on behavior in the elevated plusmaze model of anxiety. These findings are discussed in relation to coping mechanisms in murine “victims” of aggression. © 1995 Wiley-Liss, Inc.  相似文献   

14.
N‐Methyl‐D ‐aspartate (NMDA) receptor antagonists are perspective candidates for medication development for a number of diseases/states that are associated with increased aggressiveness (e.g., opioid withdrawal). The prototypic NMDA receptor antagonist phencyclidine (PCP) itself is a widely abused substance and is known to elevate levels of aggression in drug users. The present study was aimed at testing several drugs that share with PCP the ability to block NMDA receptor–associated channel. The resident‐intruder procedure was used to assess drug effects on aggressive behavior in isolated male mice. Resident aggressive mice were administered NMDA channel blockers (PCP; 0.3–10 mg/kg), dizocilpine (MK‐801; 0.01–0.3 mg/kg), memantine (1–30 mg/kg), and MRZ 2/579 (0.1–5.6 mg/kg). The competitive NMDA receptor antagonist D CPPene (0.1–5.6 mg/kg) was also tested as a compound representing an alternative approach to reduce activity of NMDA receptor complex. PCP, dizocilpine, and memantine inhibited expression of aggressive behaviors only at doses that produced ataxia. The novel channel blocker MRZ 2/579 also produced ataxia at the highest dose level but failed to affect aggressiveness. Reduction in aggression with a corresponding increase in sociability was observed after administration of D ‐CPPene. Overall, the present results suggest that NMDA receptor channel blockers do not exert selective effects on aggressive behavior. Aggr. Behav. 25:381–396, 1999. © 1999 Wiley‐Liss, Inc.  相似文献   

15.
The study was designed to assess whether repeated administration of diazepam (Valium®, Roche)—a benzodiazepine exerting an agonist action on GABAA receptors—may alleviate both the short (1 week, 1W) and long-term (6 weeks, 6W) deleterious effects of alcohol withdrawal occurring after chronic alcohol consumption (6 months; 12% v/v) in C57/BL6 male mice. More pointedly, we first evidenced that 1W and 6W alcohol-withdrawn mice exhibited working memory deficits in a sequential alternation task, associated with sustained exaggerated corticosterone rise and decreased pCREB levels in the prefrontal cortex (PFC). In a subsequent experiment, diazepam was administered i.p. for 9 consecutive days (1 injection/day) during the alcohol withdrawal period at decreasing doses ranging from 1.0 mg/kg to 0.25 mg/kg. Diazepam was not detected in the blood of withdrawn mice at the time of memory testing, occurring 24 hours after the last diazepam injection. Repeated diazepam administration significantly improved alternation rates and normalized levels of glucocorticoids and pCREB activity in the PFC in 1W but not in 6W withdrawn mice. Thus, repeated diazepam administration during the alcohol-withdrawal period only transitorily canceled out the working memory impairments and glucocorticoid alterations in the PFC of alcohol-withdrawn animals.  相似文献   

16.
The neurosteroid dehydroepiandrosterone (DHEA) is a powerful inhibitor of aggression in murine models when given for 15 days and potentially may be useful in the management of inappropriate human aggression. Although the biosynthesis and metabolism of DHEA have been described, little is known about the potential effect of the steroidal environment during sexual differentiation on the subsequent response to DHEA. Whether prenatal androgen exposure influences the subsequent response to DHEA was assessed by comparing the effect of DHEA (80 μg/d) on aggression in female offspring where dams were treated with 1, 10, or 100 μg of testosterone (T) on days 15 to 18 of gestation (Experiment I) or that developed in different uterine positions (Experiment II). The results showed that DHEA decreased attack behavior in general and that the 100‐μg prenatal T treatments enhanced the antiaggressive effect of this neurosteroid. Neither the lower doses of exogenously administered T nor the uterine position led to an enhanced response to DHEA. In addition, whether DHEA produced changes in social and nonsocial activities was examined. In the 100‐μg T females, DHEA increased the duration of the former and decreased the frequency and duration of the latter, indicating that it was not a general decrement in behavioral expression that mediated the enhanced response to the antiaggressive effect of DHEA. In the second experiment, DHEA treatment led to increased frequencies of social nonaggressive and nonsocial activities. However, the uterine positions × treatment interactions were not significant, demonstrating that contiguity to male fetuses did not differentially affect the response to DHEA. Aggr. Behav. 27:130–138, 2001. © 2001 Wiley‐Liss, Inc.  相似文献   

17.
These experiments examined the effect of the GABAA, agonist, muscimol (MUS), on memory for changes in reward magnitude. In Experiment 1 rats were trained to run a straight alley for either a large or small food reward. After reaching asymptotic performance rats in the high reward group were shifted to the small food reward. Half the animals received 1.0 or 3.0 mg/kg (ip) of MUS or the equivalent volume of saline immediately after training. Shifted training continued for 3 more days and no further injections were given. Shifted saline animals displayed an increase in response latencies compared to unshifted controls with a sharp peak on the day after the shift. Shifted MUS receiving 1.0 mg/kg performed comparably to shifted saline animals. In contrast, shifted MUS animals receiving 3.0 mg/kg displayed performance comparable to shifted saline animals on the day of the shift but displayed a sharp increase in response latencies on the second day after the shift. These findings indicate that post-training systemic MUS injections delay the peak increase in response latencies and suggest that MUS induces retrograde amnesia for reward reduction. Experiment 2 examined the effect of MUS on the memory of a reward increase. Rats were first trained as in Experiment 1 and rats under the high reward condition were then shifted to the small reward. On the next training session, the large food reward was reinstated. Immediately after the session all animals were injected with saline or 3.0 mg/kg of MUS. The large food reward was continued for the remainder of training and no further injections were given. On the following session, the performance of the shifted saline animals was comparable to that of the unshifted controls while shifted MUS animals displayed significantly higher response latencies. The findings that MUS prevented the reduction in response latencies seen in saline-injected animals suggest that MUS also induces retrograde amnesia for reward increases.  相似文献   

18.
The endogenous polyamine agmatine may be a new central neurotransmitter. Agmatine‐like immunoreactivity has been described in numerous brain regions (such as the hypothalamus and amygdala), long thought involved in the control of aggression. Consequently, the present study examined agmatine's (2.5–80 mg/kg, ip) effects on behavior directed by isolated male mice to anosmic partners in a neutral area. The videotaped encounters were analysed in terms of 10 broad behavioral categories. Agmatine did not appear to be involved in the modulation of aggression or anxiety in this test. Aggr. Behav. 31:000000, 2005. © 2005 Wiley‐Liss, Inc.  相似文献   

19.
Drugs with multiple actions can have complex discriminative‐stimulus properties. An approach to studying such drugs is to train subjects to discriminate among drug combinations and individual drugs in the combination so that all of the complex discriminative stimuli are present during training. In the current experiments, a four‐choice procedure was used to train pigeons to discriminate among dizocilpine (noncompetitive NMDA receptor blocker), pentobarbital (GABAA receptor agonist), a fixed‐dose combination of these two drugs, and saline. Following extended training, low doses of pentobarbital or dizocilpine administered alone produced saline‐appropriate responding. Higher doses of pentobarbital produced responding on the pentobarbital‐appropriate key and higher doses of dizocilpine produced responding on the dizocilpine key. Administering the lowest doses of pentobarbital and dizocilpine together resulted in responding on the saline‐appropriate key. Increasing the dose of pentobarbital in the presence of low doses of dizocilpine produced responding primarily on the pentobarbital‐appropriate key; increasing the dose of dizocilpine in the presence of the lowest dose of pentobarbital produced responding primarily on the dizocilpine‐appropriate key. Combining the higher doses of pentobarbital and dizocilpine resulted in responding primarily on the drug‐combination key. Low doses of phencyclidine or ethanol produced responding on the saline‐appropriate key, but intermediate doses resulted in individual subjects responding predominately on either the pentobarbital key, the dizocilpine key, or the drug‐combination key depending on the subject. After the highest dose of phencyclidine or ethanol, most subjects responded predominantly on the drug‐combination key. Low doses of other drugs tested produced responding on the saline‐appropriate key. With the highest diazepam doses responding was largely confined to the pentobarbital‐appropriate key. The highest doses of dextromethorphan or dextrorphan resulted in responding on the dizocilpine key more frequently than on other keys. Across a range of doses, morphine produced responding predominantly on the saline key. The results using the four‐key procedure emphasized the role of both GABAA and NMDA receptors in the complex discriminative stimulus properties of phencyclidine and of ethanol.  相似文献   

20.
This paper describes the development of a psychometric measure of indirect aggression for use in an adult population. Items were generated from a series of qualitative interviews. Two versions of the scale were developed; the Indirect Aggression Scale Aggressor version (IAS‐A) and Target version (IAS‐T). Both versions of the scale were administered to separate samples (nA=294; nT=294). Scales were analysed using item analysis of internal consistency, as well as exploratory factor analysis. Both versions were found to have the same consistent three sub‐scales: social exclusion, use of malicious humour, and guilt induction. Preliminary psychometric evaluation suggests that the scales are both sufficiently reliable (with Cronbach's alphas ranging from .81 to .89) and valid. There were no gender differences in either using or being the victim of indirect aggression, and the behaviour was significantly negatively correlated with age. Future validation and potential usage of the measures are discussed. Aggress. Behav. 31:1–14, 2005. © 2005 Wiley‐Liss, Inc.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号