Social isolation at adolescence: a systematic review on behaviour related to cocaine, amphetamine and nicotine use in rats and mice.

Adolescence is known for its high level of risk-taking, and neurobiological alterations during this period may predispose to psychoactive drug initiation and progression into more severe use patterns. Stress is a risk factor for drug consumption, and post-weaning social isolation increases drug self-administration in rodents. This review aimed to provide an overview of the effects of adolescent social isolation on cocaine, amphetamine and nicotine use-related behaviours, highlighting the specific period when animals were submitted to stress and these drugs. We wondered if there was a specific period during adolescence that isolation stress would increase drug use vulnerability. A total of 323 publications from the Scopus, Web of Science and PubMed (Medline) electronic databases were identified using the words "social isolation" and "adolescence" and "drug" or "cocaine" or "amphetamine" or "nicotine", resulting in 24 articles after analyses criteria following the PRISMA statement. The main points raised were social isolation during adolescence increased cocaine self-administration, amphetamine and nicotine locomotor activity. We did not observe a pattern of a specific moment during the adolescent period that could lead to an increased vulnerability to drug use. The precise conditions under which adolescent social stress alters drug use parameters are complex and likely depend on several factors.

Stress in neonatal rats with different maternal care backgrounds: monoaminergic and hormonal responses.

The first 2 weeks of life in rats are known as the stress hyporesponsive period because stress responses in pups are diminished as compared to adult animals. However, it is considered a critical period in development in which infant rats are susceptible to environmental events, such as stressful stimuli and quality of maternal care received. These early life events have long-lasting effects, shaping a variety of outcomes, such as stress responsivity. This study investigated the effects of maternal care and sex differences on the response to an aversive stimulus in rat pups from high (HL) and low licking (LL) mothers. Plasma corticosterone, oxytocin (OT), and central monoaminergic activity in 13-day-old rats submitted to cold stress were analyzed. Stress increased plasma corticosterone and marginally decreased hypothalamic dihydroxyphenylacetic acid/dopamine ratio. HL pups showed higher levels of plasma OT than LL pups. The maternal effect was also detected in the hippocampus, in which 5-hydroxyindole-3-acetic acid/serotonin ratio was increased in HL pups, independently of the sex and stress. Investigating the early life events is useful not only into understand the neurobiological and hormonal mechanisms underlying maternal and stressful influences on infant development into a healthy or psychopathological adult phenotype, but also to unveil the immediate outcomes on infancy.

Stress in Neonatal Rats with Different Maternal Care Backgrounds: Monoaminergic and Hormonal Responses.

The first 2 weeks of life in rats are known as the stress hyporesponsive period because stress responses in pups are diminished as compared to adult animals. However, it is considered a critical period in development in which infant rats are susceptible to environmental events, such as stressful stimuli and quality of maternal care received. These early life events have long-lasting effects, shaping a variety of outcomes, such as stress responsivity. This study investigated the effects of maternal care and sex differences on the response to an aversive stimulus in rat pups from high (HL) and low licking (LL) mothers. Plasma corticosterone, oxytocin, and central monoaminergic activity in 13-day-old rats submitted to cold stress were analyzed. Stress increased plasma corticosterone and marginally decreased hypothalamic dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio. HL pups showed higher levels of plasma oxytocin than LL pups. The maternal effect was also detected in the hippocampus, in which 5-hydroxyindole-3-acetic acid/serotonin (5-HIAA/5-HT) ratio was increased in HL pups, independently of the sex and stress. Investigating the early life events is useful not only into understand the neurobiological and hormonal mechanisms underlying maternal and stressful influences on infant development into a healthy or psychopathological adult phenotype, but also to unveil the immediate outcomes on infancy.

Flunitrazepam in combination with alcohol engenders high levels of aggression in mice and rats.

RATIONALE: Higher doses of benzodiazepines and alcohol induce sedation and sleep; however, in low to moderate doses these drugs can increase aggressive behavior. OBJECTIVES: To assess firstly the effects of ethanol, secondly the effects of flunitrazepam, a so-called club drug, and thirdly the effects of flunitrazepam plus alcohol on aggression in mice and rats. METHODS: Exhaustive behavioral records of confrontations between a male resident and a male intruder were obtained twice a week, using CF-1 mice and Wistar rats. The salient aggressive and non-aggressive elements in the resident's repertoire were analyzed. Initially, the effects of ethanol (1.0g/kg), and secondly flunitrazepam (0; 0.01; 0.1; and 0.3mg/kg) were determined in all mice and rats; subsequently, flunitrazepam or vehicle, given intraperitoneally (0; 0.01; 0.1; and 0.3mg/kg) was administered plus ethanol 1.0g/kg or vehicle via gavage. RESULTS: The most significant finding is the escalation of aggression after a moderate dose of ethanol, and a low dose of flunitrazepam. The largest increase in aggressive behavior occurred after combined flunitrazepam plus ethanol treatment in mice and rats. CONCLUSIONS: Ethanol can heighten aggressive behavior and flunitrazepam further increases this effect in male mice and rats.

On the absence of mutations in nucleotide excision repair genes in sporadic solid tumors.

In general, stochastic tumors show genomic instability associated with the proliferation of DNA point mutations, that is, a mutator phenotype. This feature cannot be explained by a dysfunctional mismatch repair alone, and indicates that nucleotide excision repair (NER) and/or base excision repair should be suppressed. However, mutations in NER genes are not causally implicated in the oncogenesis of sporadic solid tumors, according to the Cancer Gene Census at http://www.sanger.ac.uk/genetics/CGP/Census/. This brings up an apparent paradox: how to explain the recurrent non-existence in NER genes of somatic mutations causally related to cancer? In a recent study, we have shown that the origin of point mutations in cancer cell genomes can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with a disabled apoptosis gene network. In the present study, we further characterize NER gene network properties and show that it has a highly connected architecture. This feature suggests that the absence of mutations in NER genes in sporadic solid tumors is a result of their participation in many essential cellular functions.

On the absence of mutations in nucleotide excision repair genes in sporadic solid tumors

In general, stochastic tumors show genomic instability associated with the proliferation of DNA point mutations, that is, a mutator phenotype. This feature cannot be explained by a dysfunctional mismatch repair alone, and indicates that nucleotide excision repair (NER) and/or base excision repair should be suppressed. However, mutations in NER genes are not causally implicated in the oncogenesis of sporadic solid tumors, according to the Cancer Gene Census at http://www.sanger.ac.uk/genetics/CGP/Census/. This brings up an apparent paradox: how to explain the recurrent non-existence in NER genes of somatic mutations causally related to cancer? In a recent study, we have shown that the origin of point mutations in cancer cell genomes can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with a disabled apoptosis gene network. In the present study, we further characterize NER gene network properties and show that it has a highly connected architecture. This feature suggests that the absence of mutations in NER genes in sporadic solid tumors is a result of their participation in many essential cellular functions.

Concatenated retrieval of correlated stored information in neural networks.

We consider a coupled map lattice defined on a hypercube in M dimensions, taken here as the information space, to model memory retrieval and information association by a neural network. We assume that both neuronal activity and spike timing may carry information. In this model the state of the network at a given time t is completely determined by the intensity y(sigma,t) with which the information pattern represented by the integer sigma is being expressed by the network. Logistic maps, coupled in the information space, are used to describe the evolution of the intensity function y(sigma(upper arrow),t) with the intent to model memory retrieval in neural systems. We calculate the phase diagram of the system regarding the model ability to work as an associative memory. We show that this model is capable of retrieving simultaneously a correlated set of memories, after a relatively long transient that may be associated to the retrieving of concatenated memorized patterns that lead to a final attractor.

Coarsening of three-dimensional grains in crystals, or bubbles in dry foams, tends towards a universal, statistically scale-invariant regime.

We perform extensive Potts model simulations of three-dimensional dry foam coarsening. Starting with 2.25 million bubbles, we have enough statistics to fulfill the three constraints required for the study of statistical scale invariance: first, enough time for the transient to end and reach the scaling state; then, enough time in the scaling state itself to characterize its properties; and finally, enough bubbles at the end to avoid spurious finite size effects. In the scaling state, we find that the average surface area of the bubbles increases linearly with time. The geometry (bubble shape and size) and topology (number of faces and edges), as well as their correlations, become constant in time. Their distributions agree with the data of the literature. We present an analytical model (universal, up to parameters extracted from the simulations) for a disordered foam minimizing its free energy, which agrees with the simulations. We discuss the limitations of the simulations and of the model.

5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice.

RATIONALE: Systemic injections of 5-HT(1B) receptor agonists have been shown to have specific anti-aggressive effects in aggressive individuals. One site of action for these drugs is the 5-HT(1B) receptors in the ventral orbitofrontal cortex (VO PFC), an area that has been implicated in the inhibitory control of behavior and is a terminal region for 5-HT projections. OBJECTIVE: To assess the anti-aggressive effects of the 5-HT(1B) receptor agonist CP-94,253 when microinjected into the VO PFC (0.1, 0.56, and 1.0 microg/0.2 microl) or into the infralimbic prefrontal cortex (IL PFC; 1.0 microg/0.2 microl) in separate groups of aggressive resident male mice. To confirm the 5-HT(1B) receptor as the critical site of action for the anti-aggressive effects, the 5-HT(1B/D) antagonist GR-127,935 was microinjected at 10.0 microg/0.2 microl into the VO PFC. After recovery from surgery, the anti-aggressive effects of microinjected CP-94,253 were studied during 5-min resident-intruder confrontations that were recorded and analyzed. RESULTS: Microinjections of CP-94,253 (0.56 and 1.0 microg/0.2 microl) dose-dependently reduced the frequency of attack bites and sideways threats. This effect was behaviorally specific because non-aggressive motor activities were not significantly altered by the drug. In the IL vmPFC or in an area lateral to the VO PFC, CP-94,253 (1.0 microg/0.2 microl) did not have significant behavioral effects. CONCLUSIONS: The results highlight the 5-HT(1B) receptors in the VO PFC as a particularly important site for the inhibition of species-typical aggressive behavior in male mice.

Maternal aggression in Wistar rats: effect of 5-HT2A/2C receptor agonist and antagonist microinjected into the dorsal periaqueductal gray matter and medial septum.

The objective of the present study was to assess the role of the 5-HT2A/2C receptor at two specific brain sites, i.e., the dorsal periaqueductal gray matter (DPAG) and the medial septal (MS) area, in maternal aggressive behavior after the microinjection of either a 5-HT2A/2C receptor agonist or antagonist. Female Wistar rats were microinjected on the 7th postpartum day with the selective agonist alpha-methyl-5-hydroxytryptamine maleate (5-HT2A/2C) or the antagonist 5-HT2A/2C, ketanserin. The agonist was injected into the DPAG at 0.2 (N = 9), 0.5 (N = 10), and 1.0 microg/0.2 microl (N = 9), and the antagonist was injected at 1.0 microg/0.2 microl (N = 9). The agonist was injected into the medial septal area (MS) at 0.2 (N = 9), 0.5 (N = 7), and 1.0 microg/0.2 microl (N = 6) and the antagonist was injected at 1.0 microg/0.2 microl (N = 5). For the control, saline was injected into the DPAG (N = 7) and the MS (N = 12). Both areas are related to aggressive behavior and contain a high density of 5-HT receptors. Non-aggressive behaviors such as horizontal locomotion (walking) and social investigation and aggressive behaviors such as lateral threat (aggressive posture), attacks (frontal and lateral), and biting the intruder were analyzed when a male intruder was placed into the female resident's cage. For each brain area studied, the frequency of the behaviors was compared among the various treatments by analysis of variance. The results showed a decrease in maternal aggressive behavior (number of bites directed at the intruder) after microinjection of the agonist at 0.2 and 1.0 microg/0.2 microl (1.6 +/- 0.7 and 0.9 +/- 0.3) into the DPAG compared to the saline group (5.5 +/- 1.1). There was no dose-response relationship with the agonist. The present findings suggest that the 5-HT2A/2C receptor agonist has an inhibitory effect on maternal aggressive behavior when microinjected into the DPAG and no effect when microinjected into the MS. Ketanserin (1.0 microg/0.2 microl) decreased locomotion when microinjected into the DPAG and MS, but did not affect aggressive behavior. We interpret these findings as evidence for a specific role of 5-HT2A/2C receptors in the DPAG in the inhibition of female aggressive behavior, dissociated from those on motor activity.

Information space dynamics for neural networks.

We propose a coupled map lattice defined on a hypercube in M dimensions, the information space, to model memory retrieval by a neural network. We consider that both neuronal activity and the spiking phase may carry information. In this model the state of the network at a given time t is completely determined by a function y(sigma-->,t) of the bit strings sigma-->=(sigma1,sigma2,...,sigmaM), where sigma(i)=+/-1 with i=1,2, ...,M, that gives the intensity with which the information sigma--> is being expressed by the network. As an example, we consider logistic maps, coupled in the information space, to describe the evolution of the intensity function y(sigma-->,t). We propose an interpretation of the maps in terms of the physiological state of the neurons and the coupling between them, obtain Hebb-like learning rules, show that the model works as an associative memory, numerically investigate the capacity of the network and the size of the basins of attraction, and estimate finite size effects. We finally show that the model, when exposed to sequences of uncorrelated stimuli, shows recency and latency effects that depend on the noise level, delay time of measurement, and stimulus intensity.

Oral drug self-administration in the home cage of mice: alcohol-heightened aggression and inhibition by the 5-HT1B agonist anpirtoline.

RATIONALE: In order to model heightened aggression after alcohol consumption and to study the inhibitory influence of 5-HT1B receptors on drinking and fighting, an experimental procedure should enable self-administration of precise amounts of alcohol in a limited period of time before an aggressive confrontation. OBJECTIVES: To design a new device that can reinforce operant responding by the delivery of sweet alcohol in the resident mouse home cage, where aggressive behavior toward an intruder can subsequently be examined, and to demonstrate inhibition of alcohol-heightened aggression by 5-HT1B receptor agonist treatment. METHODS: Within one experimental session, all singly housed CFW male mice (n=26) performed a nose-poke response that was reinforced by 0.05 ml sucrose. Using the sucrose fading technique, eventually the mice consumed a 6% ethanol/4% sucrose solution after each fifth nose poke during daily 15-min experimental sessions. The number of ethanol reinforcements was adjusted so that 0.6, 1.0, 1.7, and 3.0-g/kg doses were consumed in 15 min or less. Assays confirmed blood alcohol levels at 68.1 mg/dl for intake of 1.0 g/kg. After consuming a specific dose of ethanol in the form of a fixed number of response-dependent deliveries, the response panel was removed from the home cage and, 15 min later, the resident confronted a male intruder. Anpirtoline was administered either before alcohol self-administration or before the aggressive confrontation. RESULTS: After being reinforced with 1.0 g/kg or 1.7 g/kg sweet ethanol, the mice significantly increased attack and threat behavior relative to their aggressive behavior following sucrose or water consumption only. Treatment with the 5-HT1B receptor agonist anpirtoline (0.125, 0.25, 0.5 mg/kg, i.p.) before the confrontation decreased alcohol-heightened aggression and species-typical aggression in the absence of changes in other elements of the behavioral repertoire. Anpirtoline affected ethanol-reinforced behavior only at doses that were 5-10 times higher than those producing anti-aggressive effects. CONCLUSIONS: Self-administration of alcohol in the home cage of mice is readily accomplished with the aid of a simple, removable panel. The effective inhibition of high levels of aggressive behavior due to alcohol consumption after anpirtoline treatment confirm the 5-HT1B receptor as a critical site in the termination of aggression.

Zolmitriptan--a 5-HT1B/D agonist, alcohol, and aggression in mice.

RATIONALE: Zolmitriptan is an anti-migraine agent with action at 5-HT1B/D receptors. It penetrates into the central nervous system and, like other 5-HT1B/D agonists, its pharmacotherapeutic profile may include significant anti-aggressive effects. OBJECTIVES: To examine whether zolmitriptan has potential anti-aggressive effects by studying two kinds of aggressive behavior in mice--species-typical and aggression under the influence of alcohol. A second objective was to study whether pre- or post-synaptic receptors mediate these anti-aggressive effects. METHODS: Initially, the anti-aggressive effects of zolmitriptan were studied in male CFW mice during 5-min resident-intruder confrontations. To confirm the 5-HT1B receptor as a critical site of action for the anti-aggressive effects, the zolmitriptan dose-effect determinations were repeated after pretreatment with GR 127935 (10 mg/kg, i.p.). In further experiments, mice were treated concurrently with alcohol (1.0 g/kg, p.o.) and zolmitriptan (1-30 mg/kg, i.p.) in order to compare the effects of this agonist on species-typical and alcohol-heightened aggression. Finally, mice were infused with the neurotoxin 5,7-DHT (10 microg) into the raphé area to eliminate somatodendritic and presynaptic autoreceptors. The anti-aggressive effects of zolmitriptan (17 mg/kg, i.p.) or CP-94,253 (10 mg/kg, i.p.) were assessed 10 days after the lesion, and levels of 5-HT and 5-HIAA were measured in the hippocampus and prefrontal cortex. RESULTS: Zolmitriptan exerted behaviorally specific anti-aggressive effects. The reduction in aggression was antagonized by GR 127935, indicated by a rightward shift in the dose-effect curves of zolmitriptan, showing the specificity for the 5-HT1B receptors. Zolmitriptan also decreased alcohol-heightened aggression with equal efficacy. The anti-aggressive effects of CP-94,253 and zolmitriptan remained unaltered by 5,7-DHT lesions that depleted cortical and hippocampal 5-HT by 60-80%. CONCLUSIONS: Zolmitriptan proved to be an effective and behaviorally specific anti-aggressive agent in situations that engender moderate and alcohol-heightened levels of aggression. These effects are potentially due to activation of post-synaptic 5-HT1BD receptors.

Surgical repair of a pseudoaneurysm of the ascending aorta after aortic valve replacement.

We report the case of a patient with a pseudoaneurysm of the ascending aortic clinically diagnosed 5 months after surgical replacement of the aortic valve. Diagnosis was confirmed with the aid of two-dimensional echocardiography and helicoidal angiotomography. The corrective surgery, which consisted of a reinforced suture of the communication with the ascending aorta after opening and aspiration of the cavity of the pseudoaneurysm, was successfully performed through a complete sternotomy using extracorporeal circulation, femorofemoral cannulation, and moderate hypothermia, with no aortic clamping.

Atomic transport and chemical stability during annealing of ultrathin Al2O3 films on Si.

Ultrathin films of Al2O3 deposited on Si were submitted to rapid thermal annealing in vacuum or in oxygen atmosphere, in the temperature range from 600 to 800 degrees C. Nuclear reaction profiling with subnanometric depth resolution evidenced mobility of O, Al, and Si species, and angle-resolved x-ray photoelectron spectroscopy revealed the formation of Si-Al-O compounds in near-surface regions, under oxidizing atmosphere at and above 700 degrees C. Under vacuum annealing all species remained essentially immobile. A model is presented based on diffusion-reaction equations capable of explaining the mobilities and reproducing the obtained profiles.

[Management of arterial hypertension in patients with acute ischemic stroke]. / Manejo da hipertensão arterial na isquemia cerebral aguda.

PURPOSE: We aimed with study to assess the current clinical practice about the management of high blood pressure in patients in the acute phase of ischemic stroke. We also comment some topics of ischemic stroke treatment. METHODS: A case report of a patient admitted 8 hours after onset of ischemic stroke and with blood pressure of 186 x 110 mmHg was presented to 120 surgeons and clinician. They were asked to decide the best therapeutic option: to increase, decrease or maintenance blood pressure. RESULTS: Thirty-eight physicians (31.7%) considered decreasing blood pressure the best therapeutics, 82 (68.3%) considered maintenance and none decided to increase it (p < 0.05). There was no difference between the two specialties conduct. The physicians, with more than 10 years of graduation, had a tendency to decrease the blood pressure (p < 0.05). CONCLUSION: The maintenance of blood pressure may present a sufficient blood support to compensate brain flow. A high percentage of the physicians (31.7%) do not know about the current concepts of therapeutics considering hypertension in acute ischemic stroke. The development on special units to treat these patients ("stroke units") may eventually decrease the morbimortality rates of ischemic stroke.

8-OH-DPAT in the median raphe nucleus decreases while in the medial septal area it may increase anxiety in female rats.

The experiment evaluated the effects of 8-OH-DPAT on the activity of virgin female rats (diestrus) in the elevated plus maze. The 5-HT1A receptor agonist was infused into the median raphe nucleus (N = 60) and medial septal area (N = 68) 10 min before the test. Five groups for each brain area were analyzed: intact, saline (0.2 microl) and 8-OH-DPAT (0.2; 0.5 and 2.0 microg rat(-1)). The following measures were recorded: number of entries onto open and enclosed arms and time spent on the open and enclosed arms. In addition, the frequency of stretch-attend and head-dipping were also evaluated. The results showed that in the median raphe nucleus only the highest dose of 8-OH-DPAT (2.0 microg) increased the percentage of time spent on the open arms. On the other hand, in medial septal area 8-OH-DPAT in the dose of 0.5 microg decreased the percentage of time spent on the open arms, while the doses of 0.2 and 2.0 microg had no significant impact on anxiety. Data suggest that 8-OH-DPAT acting on 5-HT1A somatodendritic autoreceptors decreases anxiety. However, at a specific dosage and acting on postsynaptic receptors of the medial septal area, 8-OH-DPAT can increase anxiety.

8-OH-DPAT in the median raphe, dorsal periaqueductal gray and corticomedial amygdala nucleus decreases, but in the medial septal area it can increase maternal aggressive behavior in rats.

The purpose of the present study was to analyze the role of somatodendritic autoreceptors and postsynaptic 5-HT1A receptors in the modulation of maternal aggressive behavior. The 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) was microinjected (0.2, 0.5 and 2.0 microg/0.2 microl) in different brain areas of female Wistar rats: median raphe nucleus (MnR); medial septal area (MS); anterior corticomedial amygdaloid nucleus (ACoM); and dorsal periaqueductal gray (DPAG). The behaviors of lactating female rats with pups against a conspecific male intruder were recorded on day 7 post-partum. Results showed that in the median raphe nuclei, in the dorsal periaqueductal gray and in the corticomedial amygdaloid nucleus 8-OH-DPAT decreased maternal aggression; while in the medial septum, the intermediate dose (0.5 microg/0.2 microl) of the 5-HT1A receptor agonist increased the aggressive behavior of the lactating female rat. It is concluded that the main role of the 5-HT1A somatodendritic autoreceptors and the post-synaptic receptors of the brain areas studied is to decrease maternal aggression, however, at a specific dosage, 8-OH-DPAT acting on postsynaptic receptors of the medial septal area can increase aggressiveness.

Territorial aggression, body weight, carbohydrate metabolism and testosterone levels of wild rats maintained in laboratory colonies.

Aggressive territorial behavior was studied in 15 colonies of wild rats (Rattus norvegicus), each consisting of 2 males and 1 female. One of the males attacked an intruder rat more frequently and had a higher body weight than the less aggressive one. In another experiment, male and female rats were raised in colonies from weaning to adulthood. Animals were weighed every 7 days until 90 days of age when plasma testosterone was measured in males, and plasma glucose, hepatic and muscle glycogen were measured in both males and females. THe heavier (and thus possibly dominant) males in the colonies of 3 males and 1 female also had a higher body weight than males raised with females, but without any male partner. In this long-term social relationship there were no significant differences in carbohydrate metabolism among the animals. The differential growth rate among males was established around the period of sexual maturity. Moreover, when adult, heavier males had higher plasma testosterone levels compared to the other members of the colony and also to males that had no other competitive male partner. This higher androgenic hormone level may be one of the causal factors involved in the weight increase of the dominant male in the colony.

Effects of intracerebroventricular administration of 5-HT receptor agonists on the maternal aggression of rats.

This study attempted to analyze the effects of 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), TFMPP (1-(3-trifluoromethyl-phenyl)piperazine hydrochloride), and DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) on maternal aggressive behavior. Female Wistar rats were divided into 4 groups of 12 animals each. They received an intracerebroventricular (i.c.v.) injection of: (1) saline, (2) 8-OH-DPAT (20 micrograms/rat), (3) TFMPP (100 micrograms/rat), and (4) DOI (100 micrograms/rat). 5-HT1A (8-OH-DPAT) and 5-HT2 (DOI) receptor agonists decreased the frequency of attack 15 but not 55 min after i.c.v. injection. The 5-HT1B/D receptor agonist (TFMPP), in the dose studied, showed no significant difference as compared to saline. Pup care and non-aggressive social interaction with the intruder were not affected by any drug. These data suggest that 5-HT1A and 5-HT2 receptor agonists can specifically inhibit maternal aggression without affecting maternal care; however, this effect is of short duration.