Behavioral profile of amisulpride in agonistic encounters between male mice

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.     

Behavioral profile of L–741,741, a selective D4 dopamine receptor antagonist,in social encounters between male mice

Although the role of dopamine D1–D2–D3 receptors in the modulation of aggression has been extensively documented, there is not information with respect to the implication of D4 receptor. The aim of this study was to examine the acute effects of L–741,741 (0.75, 1.5 and 3 mg/kg, i.p), a selective D4 receptor antagonist, on social encounters between male mice using an ethopharmacological approach. Ten min of diadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. These encounters were videotaped and the accumulated time allocated by subjects to ten broad behavioral categories was estimated. Besides other behaviors, the aggressive and motor behaviors were evaluated 30 min after injection using an ethologically based analysis. L–741,741 did not affect significantly offensive behaviors (threat and attack), as compared with the control group. Likewise, motor and anxiety‐related behaviors (such as social investigation, avoidance/flee or defense submission) were not altered after drug administration. These results suggest that dopamine D4 receptor is not involved in the modulation of aggressive behavior. Aggr. Behav. 29:552–557, 2003. © 2003 Wiley‐Liss, Inc.     

Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats

Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of learning processes and is important for inhibitory avoidance and conditioned taste aversion learning. MGlu5 receptors are physically connected with NMDA receptors and they interact with, and modulate, the function of one another in several brain regions. The present studies used systemic co-administration of an mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK-801) to characterize the interactions of these receptors in two aversive learning tasks. Male Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10mg/kg, s.c.), delivered by itself prior to the conditioning trial, did not have any effect on performance in either task 48 h after training. However, CDPPB (at 3mg/kg) attenuated the MK-801 (0.2mg/kg, i.p.) induced learning deficit in both tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie the importance of mGlu5 and NMDA receptor interactions in modulating memory processing, and are consistent with findings showing the efficacy of positive allosteric modulators of mGlu5 receptors in reversing the negative effects of NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor gating, or working, spatial and recognition memory.     

The influence of violent and nonviolent computer games on implicit measures of aggressiveness

We examined the causal relationship between playing violent video games and increases in aggressiveness by using implicit measures of aggressiveness, which have become important for accurately predicting impulsive behavioral tendencies. Ninety‐six adults were randomly assigned to play one of three versions of a computer game that differed only with regard to game content (violent, peaceful, or abstract game), or to work on a reading task. In the games the environmental context, mouse gestures, and physiological arousal—as indicated by heart rate and skin conductance—were kept constant. In the violent game soldiers had to be shot, in the peaceful game sunflowers had to be watered, and the abstract game simply required clicking colored triangles. Five minutes of play did not alter trait aggressiveness, yet an Implicit Association Test detected a change in implicit aggressive self‐concept. Playing a violent game produced a significant increase in implicit aggressive self‐concept relative to playing a peaceful game. The well‐controlled study closes a gap in the research on the causality of the link between violence exposure in computer games and aggressiveness with specific regard to implicit measures. We discuss the significance of importing recent social–cognitive theory into aggression research and stress the need for further development of aggression‐related implicit measures. Aggr. Behav. 36:1–13, 2010. © 2009 Wiley‐Liss, Inc.     

Effects of dizocilpine (MK801) on olfactory span in rats

NMDA receptor antagonists interfere with learning and memory in some tasks, but not others. Some recent accounts have suggested that tasks placing demands on working memory are those most likely to be affected, and the present study tested this hypothesis. The purpose of the study was to adapt a recently developed procedure designed to test working memory capacity, the olfactory memory span task, for use in behavioral pharmacology and to then determine the effects of the NMDA receptor antagonist, dizocilpine (MK801) on performance in this task. Rats were trained in a non-match-to-sample procedure under conditions in which they had to remember an increasing number of olfactory stimuli as the session progressed. Simple olfactory discrimination trials were interspersed to provide a performance control. Effects of dizocilpine (.03, .10, .17, .3mg/kg) were determined after stable performances were obtained. Rats were able to sustain stable performances on both the span and simple discrimination tasks with average spans of about 10 items. Accuracy declined as the number of stimuli to remember increased, and dizocilpine impaired accuracy in a dose-dependent and memory-load dependent fashion. The finding that the effects of dizocilpine interacted with the number of stimuli to remember is generally consistent with hypotheses linking NMDA receptors and working memory processes.     

Manipulations of vasopressin alter aggression differently across testing conditions in monogamous and non‐monogamous Peromyscus mice

Differences in the distribution of arginine vasopressin (AVP) and a subtype of AVP receptors, the V_1a receptor, may explain dissimilarities in social behavior of monogamous and non‐monogamous rodents. Intracerebroventricular infusions of AVP and a V_1a antagonist were used in sexually naive males of two mouse species, the monogamous and highly aggressive California mouse (Peromyscus californicus) and the non‐monogamous and less aggressive white‐footed mouse (P. leucopus), to begin testing the interaction between the social system of a species and the effects of AVP on aggression. Two testing conditions, the resident‐intruder aggression test (R‐I) and the neutral arena aggression test, were used because they may differ in function and underlying biological mechanisms. In the R‐I test, administration of the antagonist lengthened attack latencies in California mice. In contrast, blocking V_1a receptors did not alter attack latencies in the R‐I test in white‐footed mice or in the neutral arena aggression test in both species. AVP also did not alter aggression in either species in either behavioral test. Overall, these results suggest that AVP may be more likely to be associated with offensive aggression as measured in the R‐I test than with neutral arena aggression and that the effects of AVP manipulations may differ between monogamous and non‐monogamous rodents. Aggress. Behav. 31:000–000, 2005. © 2005 Wiley‐Liss, Inc.     

The relationship between family aggression history and expressed aggression among college males

The relationship between family of origin aggression and aggression across numerous relationship types was examined among a sample of 197 college‐aged males. Participants completed a self‐report questionnaire assessing the frequency and severity of family aggression (aggression between parents, parental aggression directed toward participants), as well as the frequency and severity of participants' aggression across a number of relationship types (dating, friends, strangers, people in bars, co‐workers, bosses, police officers). The results of the present study indicate that a substantial proportion of college‐aged males report a history of aggressive behavior, both in dating/spousal relationship and other‐relationship types. Analyses revealed that observing parental aggression and receiving aggression from parents was related to aggression in dating relationships. However, only received aggression from parents was related to more general aggressiveness in other non–dating/spousal relationship types. The pattern of findings also suggest that it is important to assess the aggressive behavior of both parents to get a better understanding of the link between family aggression and later expressed aggression. Aggr. Behav. 25:255–267, 1999. © 1999 Wiley‐Liss, Inc.     

EFFECTS OF DRUGS AND DRUG COMBINATIONS IN PIGEONS TRAINED TO DISCRIMINAT AMONG PENTOBARBITAL,DIZOCILPINE, A COMBINATION OF THESE DRUGS,AND SALIN

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 (GABA_A 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 GABA_A and NMDA receptors in the complex discriminative stimulus properties of phencyclidine and of ethanol.     

Strain-dependent interactions between MK-801 and cocaine on retention of C57BL/6 and DBA/2 mice tested in a one-trial inhibitory avoidance task: involvement of dopaminergic mechanisms

Two sets of experiments were carried out with C57BL/6 (C57) and DBA/2 (DBA) mice tested in a one-trial inhibitory avoidance task. In the first set C57 and DBA mice were injected posttraining with saline or with the D1 DA receptor antagonist SCH 23390 and then with saline, cocaine (5 mg/kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Cocaine enhanced retention in the C57 strain and impaired it in the DBA strain, and MK-801 potentiated the effects of cocaine in both strains. Furthermore, pretreatment with SCH 23390 completely antagonized the potentiation of the effects of cocaine exerted by MK-801. In the second set of experiments mice belonging to these same two strains were injected posttraining with vehicle or with the D2 DA receptor antagonist (-)-sulpiride and then with saline, cocaine (5 mg/kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Pretreatment with the D2 DA receptor antagonist completely antagonized in both strains the potentiation of the effect of cocaine exerted by MK-801. The results of the present research show that the noncompetitive NMDA receptor antagonist MK-801 enhances the effect of cocaine on retention performance in C57 and DBA mice and that dopaminergic mechanisms are involved in this potentiation.     

Antiaggressive and motor effects of the DA release inhibitor CGS 10746B

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.     

Impairment of spontaneous alternation performance by an NMDA antagonist: attenuation with non-NMDA treatments.

N-Methyl-D-aspartate (NMDA) receptor antagonists disrupt learning on a variety of tasks. Previous findings indicate that glucose, naloxone, and physostigmine ameliorate learning deficits produced by several treatments. The present experiment examines whether these agents also reverse the amnestic effects of NMDA receptor blockade. Mice were tested for spontaneous alternation performance in a Y-maze. The animals received either saline or the NMDA antagonist, NPC 12626 (35 mg/kg, IP), 50 min prior to testing and received an additional injection of saline, glucose, naloxone, or physostigmine 30 min prior to testing. NPC 12626 significantly decreased alternation scores. Glucose (250 mg/kg), physostigmine (0.01 mg/kg), and naloxone (1 mg/kg) reversed the effects of NPC 12626. Thus, impairments of learning after NMDA receptor blockade share with other amnestic conditions the susceptibility to attenuation by glucose, naloxone, and physostigmine.     

Social‐cognitive mediators of the relation of environmental and emotion regulation factors to children's aggression

Tested a theoretical model in which social cognitions about aggression partially mediated the relation of environmental and emotion regulation factors to children's aggressive behavior. An ethnically diverse sample of 778 children (57% girls) in grades 4–6 from both urban and suburban schools participated. Measures included exposure to aggression (seeing/hearing about aggression, victimization), emotion regulation (impulsivity, anger control), social cognitions about aggression (self‐evaluation, self‐efficacy, retaliation approval, aggressive fantasizing, caring about consequences), and aggressive behavior. Results supported the hypothesis that social cognitions mediate the relations of exposure to aggression and anger control to aggressive behavior. Also, social cognitions about direct and indirect aggression differentially predicted the respective behaviors with which they are associated. That is, social cognitions about direct aggression were mediators of direct aggressive behavior, whereas social cognitions about indirect aggression were mediators of indirect aggressive behavior. Finally, gender moderated the relations among the variables such that for girls, retaliation approval beliefs were a strong mediator, whereas for boys, self‐evaluation was more important. Aggr. Behav. 30:389–408, 2004. © 2004 Wiley‐Liss, Inc.     

Antiaggressive Effects of Zolpidem and Zopiclone in Agonistic Encounters Between Male Mice

The effects of benzodiazepines on various types of aggression have been extensively studied. These substances produce their pharmacological effects by allosterically modulating the action of GABA via specific recognition sites on the GABA_A receptor called omega 1 and omega 2. The antiaggressive profile of non‐benzodiazepine compounds that also act at omega sites, such as zopiclone (a non‐selective omega 1 and 2 ligand) and zolpidem (a selective omega 1 ligand) has been scarcely explored. In this study, we examined the action of zolpidem (0.75‐3 mg/kg, intraperitoneally) and zopiclone (1.5‐6 mg/kg), 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. Acute treatment with zopiclone produced a marked antiaggressive effect, reducing offensive behaviors (threat and attack) at all doses used (1.5, 3, and 6 mg/kg) without affecting immobility. Likewise, the intermediate dose of zolpidem (1.5 mg/kg) significantly decreased aggression in a specific manner, without altering immobility, whereas the highest dose (3 mg/kg) provoked a reduction of aggression accompanied by a weak (but significant) increase of immobility. With repeated treatment, no tolerance to the antiaggressive effects of zopiclone and zolpidem was developed. It is concluded that omega sites at the GABA_A receptor could be involved in the control of aggression. Aggr. Behav. 28:416–425, 2002. © 2002 Wiley‐Liss, Inc.     

Perceiving Aggression from Facial Structure: Further Evidence for a Positive Association with Facial Width‐to‐Height Ratio and Masculinity,but not for Moderation by Self‐Reported Dominance

Recent work has indicated that individual differences in facial structure are linked to perceptions of aggressiveness. In particular, the relative width of a face [facial width‐to‐height ratio (fWHR)] has been suggested to be a reliable cue to aggressive behaviour, at least in men. Additionally, facial masculinity has been associated with perceptions of dominance, a close proxy of aggressiveness. In two studies, we assessed the robustness of this link using faces transformed along these vectors in men (Studies 1 and 2) and women (Study 2). Additionally, we examined whether individual differences in self‐reported dominance of perceivers moderated this association in order to extend previous work indicating that own dominance affects perception of such behaviour in others. Results indicated that both male and female faces with increased fWHR and increased facial masculinity were perceived as more aggressive. However, we found no systematic evidence for moderating effects of self‐reported dominance on the perception of aggression in others. Taken together, these results further support the robustness of fWHR and facial masculinity as cues to aggressiveness but question whether observers' own dominance moderates their perception of these cues in others. Copyright © 2013 European Association of Personality Psychology     

Behavioral profile of L‐655,708, a selective ligand for the benzodiazepine site of GABA‐A receptors which contain the α5 subunit,in social encounters between male mice

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.     

Strain‐specific aggressive behavior of male mice submitted to different husbandry procedures

Severe aggression within groups of male laboratory mice can cause serious welfare problems. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning and the provision of nesting material decrease aggression and stress in group‐housed male mice. In this study, the combined effect of these husbandry procedures was tested for their long‐term effect on aggression in two strains of male mice (BALB/c and CD‐1). We used postcleaning aggressive behavior, wound counts, and testosterone levels as indicators of aggressiveness. Physiological responses to social challenge were investigated through urinary corticosterone and adrenal tyrosine‐hydroxylase measurements. Furthermore, the aggression‐modulating effects of two enrichment items (ShepherdShack/DesRes and PVC tube) were explored. Marked differences were found between the two strains. CD‐1 mice were more aggressive, had higher testosterone levels but lower corticosterone levels, and had fewer wounds than BALB/c mice. However, in neither of the two strains was long‐term enrichment with nesting material and its transfer after cage cleaning effective in lasting reduction of intermale aggression. This may be explained by the fact that aggression levels were generally low. It seems that housing mice in small, socially stable groups or keeping social disturbances to a minimum considerably modulates aggression in group‐housed male mice. Mice of both strains housed in cages enriched with nesting material had lower urinary corticosterone levels than standard‐housed mice. We therefore conclude that the long‐term provision of nesting material, including the transfer of nesting material during cage cleaning, may enhance the welfare of laboratory mice. Aggr. Behav. 29:69–80, 2003. © 2002 Wiley‐Liss, Inc.     

Personality correlates of revenge‐seeking: Multidimensional links to physical aggression,impulsivity, and aggressive pleasure

People differ in how much they seek retribution for interpersonal insults, slights, rejections, and other antagonistic actions. Identifying individuals who are most prone towards such revenge‐seeking is a theoretically‐informative and potentially violence‐reducing endeavor. However, we have yet to understand the extent to which revenge‐seeking individuals exhibit specific features of aggressiveness, impulsivity, and what motivates their hunt for retribution. Toward this end, we conducted three studies (total N = 673), in which revenge‐seeking was measured alongside these other constructs. Analyses repeatedly demonstrated that revenge‐seeking was associated with greater physical (but not verbal) aggressiveness, anger, and hostility. Revenge‐seeking's link to physical aggression was partially accounted for by impulses toward enjoying aggression and the tendency to use aggression to improve mood. Dominance analyses revealed that sadism explained the most variance in revenge‐seeking. Revenge‐seeking was associated with greater impulsive responses to negative and positive affect, as well as greater premeditation of behavior. These findings paint a picture of revenge‐seekers as physically aggressive curators of anger, whose retributive acts are performed with planned malice and motivated by the act's entertaining and therapeutic qualities.

     

Aggressive behavior in children's dolls' house play

The present study addressed the question of whether there are gender and age differences in aggressive behavior when it is studied as the spontaneous expression of mental contents and not as the result of immediate social interaction. This study also investigated whether aggression, in terms of mental content, is related to temperamental aspects. Aggressive behaviors were examined in make‐believe play, in relation to age, gender, and temperament in a near‐ecological context, i.e., the Dolls' House Play. The participants, 55 boys and 47 girls, subdivided into three age levels (4 years–4 years and 6 months; 5–6 years; and 7 years and 6 months–8 years and 6 months) were requested to represent what happens in their family 1) during Mealtimes; 2) at Bedtime; 3) on the Saddest day; and 4) the Happiest day; their Dolls' House Play was then recorded. Children's temperaments were measured with the TABC‐Teachers' form [Martin, The Temperament Assessment Battery for Children, Brandon, VT: Clinical Psychology Publishing, 1998]. Data analysis was conducted considering aggressive behaviors in their distinct expressions—physical, verbal, direct, and indirect. Results revealed no statistical differences between boys and girls when all aggressive behaviors were compounded. However, when the distinct types of aggressiveness were considered, boys presented statistically higher levels of physical aggression than girls did. Moreover, boys and girls reacted with different types of aggression in the different emotional contexts created by the four episodes. Few age differences were observed. Surprisingly, there was a significantly greater presence of indirect verbal aggressiveness in younger children. With respect to temperament, a higher level of negative emotivity was significantly linked to a greater degree of aggressive behaviors in some of the episodes. In conclusion, this paper confirms gender differences in the type of aggressive behavior children display even in the absence of any immediate social interaction, which might itself trigger aggression. Aggr. Behav. 30:504–519, 2004. © 2004 Wiley‐Liss, Inc.     

Intracerebroventricular Infusion of the NMDA Receptor-Associated Glycine Site Antagonist 7-Chlorokynurenate Impairs Water Maze Performance but Fails to Block Hippocampal Long-Term Potentiation in Vivo

Most previous studies investigating the relationship betweenN-methyl- -aspartate receptor-dependent synaptic plasticity and learning have employed drugs that either compete with glutamate for access to the primary agonist binding site (e.g., -2-amino-5-phosphopentanoic acid) or block the associated ion channel (e.g., dizocilpine). This study targeted the glycine receptor site located on the NMDA receptor complex. Chronic intracerebroventricular infusion of the glycine site antagonist 7-chlorokynurenate (7CK; 75 mM, 0.5 μl/h, icv, for up to 14 days) impaired performance of male Lister hooded rats during acquisition of a spatial reference memory task in the water maze. In addition, however, these animals showed sensorimotor deficits, including a prolonged righting reflex, ataxia, and difficulty in staying on the escape platform. On completion of behavioral testing, the rats were anesthetized with urethane and an attempt was made to induce LTP in the hippocampus ipsilateral to the infusion cannula. Both control and 7CK-infused animals displayed equivalent long-term potentiation (LTP) 60 min posttetanus. A novel analytical technique for assaying drug tissue levels involving high-performance liquid chromotography with fluorescence detection revealed that tissue levels of 7CK in hippocampus were extremely low and unlikely to be sufficient to affect LTP, as observed. These findings neither support nor compromise the LTP/learning hypothesis, but they illustrate some of the problems of using drugs to elucidate the neurobiological mechanisms of learning and memory and the importance of a within-subjects design incorporating behavioral, physiological, and biochemical measures.     

Selective antiaggressive effect of an alpha-2 adrenoceptor agonist naphthylmedetomidine in mice

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.