Naloxone increases conditioned fear responses during social buffering in male rats.

Social buffering is the phenomenon in which the presence of an affiliative conspecific mitigates stress responses. We previously demonstrated that social buffering completely ameliorates conditioned fear responses in rats. However, the neuromodulators involved in social buffering are poorly understood. Given that opioids, dopamine, oxytocin and vasopressin play an important role in affiliative behaviour, here, we assessed the effects of the most well-known antagonists, naloxone (opioid receptor antagonist), haloperidol (dopamine D2 receptor antagonist), atosiban (oxytocin receptor antagonist) and SR49059 (vasopressin V1a receptor antagonist), on social buffering. In Experiment 1, fear-conditioned male subjects were intraperitoneally administered one of the four antagonists 25 min prior to exposure to a conditioned stimulus with an unfamiliar non-conditioned rat. Naloxone, but not the other three antagonists, increased freezing and decreased walking and investigation as compared with saline administration. In Experiment 2, identical naloxone administration did not affect locomotor activity, anxiety-like behaviour or freezing in an open-field test. In Experiment 3, after confirming that the same naloxone administration again increased conditioned fear responses, as done in Experiment 1, we measured Fos expression in 16 brain regions. Compared with saline, naloxone increased Fos expression in the paraventricular nucleus of the hypothalamus and decreased Fos expression in the nucleus accumbens shell, anterior cingulate cortex and insular cortex and tended to decrease Fos expression in the nucleus accumbens core. Based on these results, we suggest that naloxone blocks social buffering of conditioned fear responses in male rats.

Clinical usefulness of the hold-and-drag closure using the SB clip for large mucosal defects after colorectal endoscopic submucosal dissection.

BACKGROUND: Endoscopic clip closure of mucosal defects after colorectal endoscopic submucosal dissection (ESD) reduces the risk of postoperative adverse events, but achieving complete closure for large mucosal defects can be difficult. The aim of this study was to evaluate the effectiveness of the hold-and-drag closure using an SB clip compared with that of the conventional closure for mucosal defects after colorectal ESD. METHODS: Eighty-four consecutive colorectal lesions resected by ESD at the Hiroshima Asa Citizens Hospital were registered and randomly allocated to two groups (Group A: SB clip, Group B: EZ clip), and then endoscopic closures were performed. We crossed-over to the SB clip in situations where the initial closure using an EZ clip was unsuccessful in achieving complete closure. Outcomes were compared and analyzed. RESULTS: Forty-two lesions were randomly assigned to groups A and B. The complete closure rate was significantly higher in group A, especially in resected specimens with a diameter of 30 mm or more. Twelve lesions that failed complete closure in group B were changed to SB clips, and 95% of the whole of group B were successfully closed. There were no significant differences in procedural time, number of clips, and cost of clips between groups A and B. CONCLUSION: Compared with the conventional closure, the hold-and-drag closure using an SB clip is a more suitable method for complete closure, especially for large mucosal defects of 30 mm or more. Furthermore, this is a simpler and more economical compared to a zipper closure using EZ clips.

Estrogen increases KISS1 expression in newly generated immortalized KISS1-expressing cell line derived from goat preoptic area.

Kisspeptin neurons located in the hypothalamic preoptic area (POA) are suggested to be responsible for the induction of the gonadotropin-releasing hormone (GnRH) surge and the following luteinizing hormone (LH) surge to regulate female mammals' ovulation. Accumulating evidence demonstrates that the preovulatory level of estrogen activates the POA kisspeptin neurons (estrogen positive feedback), which in turn induces a GnRH/LH surge. This study aimed to derive a cell line from goat POA kisspeptin neurons as an in vitro model to analyze the estrogen positive feedback mechanism in ruminants. Neuron-derived cell clones obtained by the immortalization of POA tissue from a female Shiba goat fetus were analyzed for the expression of kisspeptin (KISS1) and estrogen receptor α (ESR1) genes using quantitative real-time reverse transcription-polymerase chain reaction and three cell clones were selected as POA kisspeptin neuron cell line candidates. One cell line (GP64) out of the three clones showed significant increase in the KISS1 level by incubation with estradiol for 24 h, indicating that the GP64 cells mimic endogenous goat POA kisspeptin neurons. The GP64 cells showed immunoreactivities for kisspeptin and estrogen receptor α and retained a stable growth rate throughout three passages. Further, intracellular calcium levels in the GP64 cells were increased by the KCl challenge, indicating their neurosecretory ability. In conclusion, we generated a new KISS1-expressing cell line derived from goat POA. The current GP64 cell line could be a useful model to elucidate the estrogen positive feedback mechanism responsible for the GnRH/LH surge generation in ruminants.

Social buffering enhances extinction of conditioned fear responses by reducing corticosterone levels in male rats.

The presence of an affiliative conspecific reduces stress responses to a wide variety of stimuli, which is termed "social buffering." We previously reported that social buffering in male rats ameliorated behavioral responses, as well as hypothalamic-pituitary-adrenal axis activation, elicited by an auditory conditioned stimulus (CS). In addition, subjects that experienced social buffering did not show stress responses when re-exposed to the CS the next day in the absence of an accompanying rat. However, the mechanisms underlying this enhancement of between-session extinction are poorly understood. In Experiment 1, we compared corticosterone levels at 0, 10, and 15 min after extinction training. Subjects that experienced social buffering had lower corticosterone levels than subjects that trained alone at the end of extinction training. However, corticosterone levels at 10 and 15 min after training were not affected by the experience of social buffering. These results suggest that a lower level of corticosterone during extinction training had an important role in the enhancement of extinction. To directly assess this, in Experiment 2, we manipulated the corticosterone level during extinction training. We found that a subcutaneous injection of corticosterone before extinction training blocked the enhancement of extinction by social buffering. These results demonstrate that the enhancement is caused by a low level of corticosterone during the training. Taken together, we suggest that social buffering enhances extinction of conditioned fear responses by reducing corticosterone levels in male rats.

[A case of ruptured posterior superior pancreaticoduodenal artery aneurysm successfully treated by emergency transcatheter embolization].

A man in his 40s with no remarkable past medical history was referred to our hospital with acute exacerbation of nonspecific epigastric pain by another hospital on the morning of the day of presentation. Though vital signs were stable, tenderness and guarding were observed over the entire abdomen. Contrast-enhanced computed tomography (CT) revealed a giant retroperitoneal hematoma due to a ruptured aneurysm close to the superior mesenteric artery. Emergency angiography of the superior mesenteric artery detected a ruptured 2-mm pseudoaneurysm of the posterior superior pancreaticoduodenal artery, for which embolization was immediately performed. The postoperative course was good, with the patient complaining only of transient abdominal pain due to exclusion of the hematoma on hospital day 6. His clinical symptoms disappeared with conservative treatment, and the patient was discharged on hospital day 18. Complete occlusion of the aneurysm and reduction of the hematoma was confirmed on follow-up CT. Pancreaticoduodenal artery aneurysm is an uncommon visceral artery aneurysm, and ruptured aneurysms typically result in fatal hemorrhage and high mortality. We herein report a case of ruptured aneurysm of the posterior pancreaticoduodenal artery where emergency transcatheter arterial embolization was able to save the patient's life. We also review 116 cases of pancreaticoduodenal artery aneurysm reported in Japanese literature.

Identification of a pheromone that increases anxiety in rats.

Chemical communication plays an important role in the social lives of various mammalian species. Some of these chemicals are called pheromones. Rats release a specific odor into the air when stressed. This stress-related odor increases the anxiety levels of other rats; therefore, it is possible that the anxiety-causing molecules are present in the stress-related odorants. Here, we have tried to identify the responsible molecules by using the acoustic startle reflex as a bioassay system to detect anxiogenic activity. After successive fractionation of the stress-related odor, we detected 4-methylpentanal and hexanal in the final fraction that still possessed anxiogenic properties. Using synthetic molecules, we found that minute amounts of the binary mixture, but not either molecule separately, increased anxiety in rats. Furthermore, we determined that the mixture increased a specific type of anxiety and evoked anxiety-related behavioral responses in an experimental model that was different from the acoustic startle reflex. Analyses of neural mechanisms proposed that the neural circuit related to anxiety was only activated when the two molecules were simultaneously perceived by two olfactory systems. We concluded that the mixture is a pheromone that increases anxiety in rats. To our knowledge, this is the first study identifying a rat pheromone. Our results could aid further research on rat pheromones, which would enhance our understanding of chemical communication in mammals.

Social buffering ameliorates conditioned fear responses in female rats.

The stress experienced by an animal is ameliorated when the animal is exposed to distressing stimuli along with a conspecific animal(s). This is known as social buffering. Previously, we found that the presence of an unfamiliar male rat induced social buffering and ameliorated conditioned fear responses of a male rat subjected to an auditory conditioned stimulus (CS). However, because our knowledge of social buffering is highly biased towards findings in male subjects, analyses using female subjects are crucial for comprehensively understanding the social buffering phenomenon. In the present studies, we assessed social buffering of conditioned fear responses in female rats. We found that the estrus cycle did not affect the intensity of the rats' fear responses to the CS or their degree of vigilance due to the presence of a conspecific animal. Based on these findings, we then assessed whether social buffering ameliorated conditioned fear responses in female rats without taking into account their estrus cycles. When fear conditioned female rats were exposed to the CS without the presence of a conspecific, they exhibited behavioral responses, including freezing, and elevated corticosterone levels. By contrast, the presence of an unfamiliar female rat suppressed these responses. Based on these findings, we conclude that social buffering can ameliorate conditioned fear responses in female rats.

The strain of an accompanying conspecific affects the efficacy of social buffering in male rats.

Social buffering is a phenomenon in which stress in an animal is ameliorated when the subject is accompanied by a conspecific animal(s) during exposure to distressing stimuli. We previously reported that in male Wistar rats, the presence of another Wistar rat mitigates conditioned fear responses to an auditory conditioned stimulus (CS). Subsequent analyses revealed several characteristics of this social buffering of conditioned fear responses. However, information regarding the specificity of accompanying conspecifics is still limited. In the present study, we assessed whether rats of other strains could induce social buffering in Wistar rats. When a fear-conditioned Wistar subject was re-exposed to the CS alone, we observed increased freezing and decreased investigation and walking, as well as elevated corticosterone levels. The presence of a Wistar, Sprague-Dawley, or Long-Evans rat blocked these responses, suggesting that social buffering was induced by these strains of rats. In contrast, a Fischer 344 rat did not induce social buffering in the Wistar subject. We further found that an inbred Lewis rat induced social buffering whereas a Brown Norway rat, a strain that has been established independently from Wistar rats, did not. These results suggest that the difference in origin, rather than the inbred or outbred status of the associate rat, seemed to account for the lack of social buffering induced by the F344 rats. Based on these findings, we conclude that strains of an accompanying conspecific can affect the efficacy of social buffering in rats.

Social buffering reduces male rats' behavioral and corticosterone responses to a conditioned stimulus.

In social species, the presence of an affiliative same-sex conspecific ameliorates acute stress responses in threatening conditions. We previously found that the presence of an unfamiliar male rat separated by a wire mesh barrier blocks the behavioral responses and Fos expression in the paraventricular nucleus of the hypothalamus (PVN) in a male subject rat that had previously been exposed to an auditory conditioned stimulus (CS) paired with foot shocks. Based on the Fos expression in the PVN, we hypothesized that the presence of a conspecific ameliorated the hypothalamic-pituitary-adrenal (HPA) axis activation and induced social buffering of conditioned fear responses. The direct evidence for this hypothesis, however, is still lacking. To clarify this point, we exposed fear-conditioned and non-conditioned subjects to the CS either alone or with a conspecific separated by a wire mesh barrier. When the fear-conditioned subject alone was re-exposed to the CS, it exhibited increased freezing, decreased sniffing, and elevated corticosterone levels. In contrast, the presence of the conspecific suppressed these behavioral and HPA axis responses to a level similar to those observed in the non-conditioned subjects. These results suggest that the presence of a conspecific suppressed the behavioral responses and HPA axis activation to the CS. The present results provide direct evidence for the existence of social buffering of conditioned fear responses in male rats.

Approach/Avoidance Behavior to Novel Objects is Correlated with the Serotonergic and Dopaminergic Systems in the Brown Rat (Rattus norvegicus).

The brown rat (Rattus norvegicus) is known to show three types of behavioral responses to novel objects. Whereas some rats are indifferent to novel objects, neophobic and neophilic rats show avoidance and approach behavior, respectively. Here, we compared the dopaminergic, serotonergic, and noradrenergic systems immunohistochemically among these rats. Trapped wild rats and laboratory rats were first individually exposed to the novel objects in their home cage. Wild rats were divided into neophobic and indifferent rats depending on their behavioral responses. Similarly, laboratory rats were divided into neophilic and indifferent rats. Consistent with the behavioral differences, in the paraventricular nucleus of the hypothalamus, Fos expression in corticotropin-releasing hormone-containing neurons was higher in the neophobic rats than in the indifferent rats. In the anterior basal amygdala, the neophobic rats showed higher Fos expression than the indifferent rats. In the posterior basal amygdala, the neophobic and neophilic rats showed lower and higher Fos expressions than the indifferent rats, respectively. When we compared the neuromodulatory systems, in the dorsal raphe, the number of serotonergic neurons and Fos expression in serotonergic neurons increased linearly from neophobic to indifferent to neophilic rats. In the ventral tegmental area, Fos expression in dopaminergic neurons was higher in the neophilic rats than in the indifferent rats. These results demonstrate that approach/avoidance behavior to novel objects is correlated with the serotonergic and dopaminergic systems in the brown rat. We propose that the serotonergic system suppresses avoidance behavior while the dopaminergic system enhances approach behavior to novel objects.

Alarm pheromone is detected by the vomeronasal organ in male rats.

It is widely known that a stressed animal releases specific pheromones, possibly for alarming nearby conspecifics. We previously investigated an alarm pheromone in male rats and found that this alarm pheromone evokes several responses, including increases in the defensive and risk assessment behaviors in a modified open-field test, and enhancement of the acoustic startle reflex. However, the role of the vomeronasal organ in these pheromone effects remains unclear. To clarify this point, vomeronasal organ-excising or sham surgeries were performed in male rats for use in 2 experimental models, after which they were exposed to alarm pheromone. We found that the vomeronasal organ-excising surgery blocked the effects of this alarm pheromone in both the modified open-field test and acoustic startle reflex test. In addition, the results of habituation/dishabituation test and soybean agglutinin binding to the accessory olfactory bulb suggested that the vomeronasal organ-excising surgery completely ablated the vomeronasal organ while preserving the functioning of the main olfactory system. From the above results, we showed that the vomeronasal organ plays an important role in alarm pheromone effects in the modified open-field test and acoustic startle reflex test.

Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan: relationship between regional prevalence and carrier frequency.

BACKGROUND: Canine GM1 gangliosidosis is a fatal disease in the Shiba Inu breed, which is one of the most popular traditional breeds in Japan and is maintained as a standard breed in many countries. Therefore, it is important to control and reduce the prevalence of GM1 gangliosidosis for maintaining the quality of this breed and to ensure supply of healthy dogs to prospective breeders and owners. This molecular epidemiological survey was performed to formulate an effective strategy for the control and prevention of this disease. RESULTS: The survey was carried out among 590 clinically unaffected Shiba Inu dogs from the 8 districts of Japan, and a genotyping test was used to determine nation-wide and regional carrier frequencies. The number and native district of affected dogs identified in 16 years from 1997 to June 2013 were also surveyed retrospectively. Of the 590 dogs examined, 6 dogs (1.02%, 6/590) were carriers: 3 dogs (2.27%, 3/132) from the Kinki district and the other 3 dogs from the Hokkaido, Kanto, and Shikoku districts. The retrospective survey revealed 23 affected dogs, among which, 19 dogs (82.6%) were born within the last 7 years. Of the 23 affected dogs, 12 dogs (52.2%) were from the Kinki district. Pedigree analysis demonstrated that all the affected dogs and carriers with the pedigree information have a close blood relationship. CONCLUSIONS: Our results showed that the current carrier frequency for GM1 gangliosidosis is on the average 1.02% in Japan and rather high in the Kinki district, which may be related to the high prevalence observed over the past 16 years in this region. This observation suggests that carrier dogs are distributed all over Japan; however, kennels in the Kinki district may face an increased risk of GM1 gangliosidosis. Therefore, for effective control and prevention of this disease, it is necessary to examine as many breeding dogs as possible from all regions of Japan, especially from kennels located in areas with high prevalence and carrier frequency.

Parallel Olfactory Systems Synergistically Activate the Posteroventral Part of the Medial Amygdala Upon Alarm Pheromone Detection in Rats.

In rats, a mixture of hexanal and 4-methylpentanal is a main component of the alarm pheromone. When detected by the main olfactory system (MOS) and the vomeronasal system, respectively, they activate the anterior part of the bed nucleus of the stria terminalis (BNSTa). Therefore, the information from the two olfactory systems is expected to be integrated before being transmitted to the BNSTa. To specify the integration site, we examined Fos expression in 16 brain regions in response to water (n = 10), hexanal (n = 9), 4-methylpentanal (n = 9), the mixture (n = 9), or the alarm pheromone (n = 9) in male rats. The posteroventral part of the medial amygdala showed increased Fos expression to hexanal and 4-methylpentanal. The expression was further increased by the mixture. Therefore, this region is suggested as the integration site. In addition, the BNSTa, paraventricular nucleus of the hypothalamus, and anteroventral, anterodorsal, and posterodorsal parts of the medial amygdala were suggested to be located downstream of the integrated site because only the mixture increased Fos expression. We suggest that the posterolateral part of the cortical amygdala is upstream of the integration site in the MOS because all stimuli increased Fos expression. The posterior part of the bed nucleus of the stria terminalis and posteromedial part of the cortical amygdala were suggested as being located upstream in the vomeronasal system because 4-methylpentanal and the mixture increased Fos expression. These results provide information about the neural pathway underlying the alarm pheromone effects.

Glutamatergic Projections from the Posterior Complex of the Anterior Olfactory Nucleus to the Amygdala Complexes.

Social buffering is a phenomenon where stress responses are ameliorated by an affiliative conspecific. Our previous findings suggest that the posterior complex of the anterior olfactory nucleus (AOP) is well positioned to participate in the neural mechanisms underlying social buffering. However, the lack of anatomical information prevents us from further estimating the role of the AOP. Here, we obtained anatomical information regarding the AOP in male rats. In Experiment 1 (n = 5), among 4',6-diamidino-2-phenylindole-positive cells in the AOP, the proportion of glutamic acid decarboxylase 67 (GAD67)-positive cells was 13.8% ± 1.2%. In Experiment 2 (n = 5), among the cells that were labeled by a retrograde tracer injected into the basolateral complex of the amygdala (BLA), the proportion of GAD67-positive cells was 18.6% ± 0.8%. In Experiment 3 (n = 5), we demonstrated the existence of cells that were labeled by the retrograde tracer injected into the posterior part of the medial amygdala (MeP), mostly into the ventral part of the MeP. In addition, the proportion of GAD67-positive cells among the tracer-labeled cells was 21.7% ± 1.7%. In Experiment 4 (n = 3), the retrograde tracers were injected into the BLA and MeP, mostly into the ventral part of the MeP. The proportion of double-labeled cells among the tracer-labeled cells was 2.1% ± 1.2%. Taken together, these results suggest that the AOP is predominantly composed of glutamatergic neurons. In addition, the AOP sends mutually independent glutamatergic-predominant projections to the BLA and MeP.

An appeasing pheromone ameliorates fear responses in the brown rat (Rattus norvegicus).

The brown rat (Rattus norvegicus) is one of the major animals both in the laboratory and in urban centers. Brown rats communicate various types of information using pheromones, the chemicals that mediate intra-species communication in minute amounts. Therefore, analyses of pheromones would further our understanding of the mode of life of rats. We show that a minute amount of 2-methylbutyric acid (2-MB) released from the neck region can ameliorate fear responses both in laboratory rats and in wild brown rats. Based on these findings, we conclude that 2-MB is an appeasing pheromone in the brown rat. A better understanding of rats themselves would allow us to perform more effective ecologically based research on social skills and pest management campaigns with low animal welfare impacts, which might contribute to furthering the advancement of science and improving public health.

The neural pathway underlying social buffering of conditioned fear responses in male rats.

In social animals, the presence of an affiliative conspecific alleviates acute stress responses, and this is termed social buffering. However, the neural mechanisms underlying social buffering have not been elucidated. We have reported that the main olfactory system mediates social buffering of conditioned fear responses in male rats, and this is accompanied by suppression of the lateral and central amygdala. Therefore, olfactory signals are probably transmitted from the main olfactory system to the amygdala. Because the lateral and central amygdala do not receive projections from the main olfactory bulb, the site that links the main olfactory bulb and amygdala was presumed to be located within the main olfactory system. To find the linkage site, we generated lesions within the main olfactory system, and found that a bilateral lesion in the posteromedial region of the olfactory peduncle (pmOP) blocked social buffering. Next, we determined that the pmOP receives direct projections from the main olfactory bulb. Finally, we demonstrated that the connection between the pmOP and ipsilateral amygdala is important for social buffering, and that the pmOP projects directly to the ipsilateral amygdala, including the lateral and central amygdala. On the basis of these results, we suggest that the pmOP links the main olfactory blub to the amygdala and enables social buffering of conditioned fear responses. These results provide the first comprehensive picture of the neural pathway underlying the social buffering phenomenon.

Central administration of neurokinin B activates kisspeptin/NKB neurons in the arcuate nucleus and stimulates luteinizing hormone secretion in ewes during the non-breeding season.

Human genetic studies have suggested that kisspeptin and neurokinin B (NKB) play pivotal roles in the control of gonadotropin-releasing hormone (GnRH) secretion. However, the role of NKB in this context is less clear compared with that of kisspeptin. In the present study, we investigated the ratio of colocalization of kisspeptin and NKB in neurons in the arcuate nucleus (ARC), the effects of intracerebroventricular infusion of NKB on luteinizing hormone (LH) secretion and whether the treatment activates ARC kisspeptin/NKB neurons in seasonally anestrous ewes. Double-labeling immunohistochemistry revealed that the majority of kisspeptin neurons coexpressed NKB in the ARC. Infusion of NKB for 2 h into the lateral ventricle elicited a discharge of LH, which resulted in significant increases in LH concentrations between 20 and 50 min after the start of infusion compared with a saline-infused control. Animals were sacrificed immediately after the end of infusion, and Fos expression in ARC kisspeptin neurons was immunohistochemically examined. The NKB treatment activated kisspeptin neurons throughout the ARC, and approximately 70% of kisspeptin neurons expressed Fos immunoreactivity at the caudal portion of the nucleus. The present study demonstrated that a central infusion of NKB elicited a discharge of LH, which was associated with the activation of a large population of ARC kisspeptin/NKB neurons in seasonally anestrous ewes. The results suggest that NKB plays a stimulatory role in the control of pulsatile GnRH secretion and that the population of ARC kisspeptin/NKB neurons is one of sites of the NKB action in sheep.

Mapping of c-Fos expression in the medial amygdala following social buffering in male rats.

Social buffering is the phenomenon in which an affiliative conspecific (associate) ameliorates stress responses of a subject. We previously found that social buffering in Wistar subject rats is induced if the strain of the associate is Wistar or a strain derived from Wistar rats. In the present study, we assessed the possible role of medial amygdala (Me) in this strain-dependent induction of social buffering. The subjects were exposed to the conditioned stimulus (CS) that had been paired or unpaired with a foot shock either alone, with an unfamiliar Wistar associate, or with an unfamiliar Fischer 344 (F344) associate. We found that the Wistar associates, but not F344 associates, ameliorated increased freezing and Fos expression in the paraventricular nucleus of the hypothalamus and lateral amygdala caused by the CS. In addition, Fos expression in the posterior complex of the anterior olfactory nucleus and lateral intercalated cell mass of the amygdala was increased simultaneously. These results suggest that Wistar associates, but not F344 associates, induced social buffering. In the Me, we did not find any differences associated with stress responses or amelioration of stress responses. In contrast, a comparison among the unpaired subjects found that the Wistar associates, but not F344 associates, increased exploratory behavior and Fos expression in the posteroventral subdivision of the Me (MePV). Based on these results, we propose that the MePV is involved in the recognition of social similarity with the associates. Taken together, the present study provides information about the possible role of Me in social buffering.

The strain of unfamiliar conspecifics affects stress identification in rats.

Humans show distinct social behaviours when we evaluate an individual as being a member of the same group and recognize social similarity to the individual. One example is more accurate identification of emotion in that individual. Our previous studies proposed that rats recognize social similarity to certain strains of unfamiliar rats. It is therefore possible that the strain of unfamiliar conspecifics affects stress identification in rats. Wistar subject rats were allowed to explore a pair of unfamiliar Wistar, Sprague-Dawley (SD), Long-Evans (LE), or Fischer344 (F344) stimulus rats. To induce differences in stress, one of the stimulus rats had received foot shocks immediately before the test. It was found that the subjects showed biased interaction towards the shocked Wistar and SD stimulus rats, but not toward the shocked LE or F344 stimulus rats. Subsequent experiments confirmed that the biased interaction towards the shocked Wistar and SD stimulus rats was driven by stress in these stimulus rats. In addition, the lack of biased interaction towards the shocked LE and F344 stimulus rats did not appear to be due to procedural reasons. The experiment using LE subject rats further confirmed that the shocked LE stimulus rats emitted distress signals. These results suggested that Wistar rats could identify stress in unfamiliar Wistar and SD rats, but not in unfamiliar LE or F344 rats. Therefore, rats appear to recognize social similarity to certain unfamiliar strains of rats.

Pretreatment with CP-154526 blocks the modifying effects of alarm pheromone on components of sexual behavior in male, but not in female, rats.

We previously demonstrated that an alarm pheromone released from male donor Wistar rats evoked several physiological and behavioral responses in recipient rats. However, the pheromone effects on social behavior were not analyzed. In the present study, we examined whether the alarm pheromone affects sexual behavior in male or female rats. When a pair of male and female subjects was exposed to the alarm pheromone during sexual behavior, the ejaculation latency was elongated, the number of mounts was increased, and the hit rate (number of intromissions/number of mounts and intromissions) was decreased in the male subject. In contrast, female sexual behavior was not affected by the alarm pheromone. When we exposed only the male or female subject of the pair to the pheromone just before sexual behavior, the results were similar: the pheromone effects were evident in male, but not in female, subjects. In addition, when we pretreated with corticotropin-releasing factor (CRF) antagonist (CP-154526) before exposing the male subject to the alarm pheromone, the pheromone effects were attenuated in a dose-dependent manner. These results indicate that the alarm pheromone modifies male, but not female, components of sexual behavior and that CRF participates in the effects.