Kimiya Narikiyo

Obese mice lacking leptin receptors showed lower struggling with longer social contact in partial gravity conditions than control lean mice

Susceptibility to stress underlies pathophysiology of various psychiatric illnesses, such as depression. Whereas dopaminergic activity is suggested to be suppressed in patients of major depression and a rodent model of depression induced by repeated stress, whether and how dopaminergic downregulation is involved in stress susceptibility remains largely unknown. Using repeated social defeat stress, we have examined a role of dopaminergic activity in stress-induced behavioral plasticity. Social defeat exposure evoked dopaminergic response in the medial prefrontal cortex (mPFC), but not in the nucleus accumbens, as measured by dopamine metabolic turnover, and that this mPFC dopaminergic response was desensitized after repeated social defeat. Notably, the level of mPFC dopaminergic activity after repeated social defeat was negatively correlated with the extent of social avoidance. C-fos immunostaining showed that repeated social defeat desensitized stressinduced response of VTA dopamine neurons. Consistent with the reported action of prostaglandin E2, a bioactive lipid, and its receptor EP1 in augmenting GABAergic inputs to midbrain dopamine neurons, the desensitization of mPFC dopaminergic activity and VTA dopamine neurons was abolished in mice lacking EP1. Concomitantly, EP1-deficient mice did not show social avoidance after repeated social defeat, and this behavioral abnormality was corrected by dopamine D1 receptor antagonist. Our data thus suggest that PGE2-EP1 signaling desensitizes stress-induced response of mesocortical dopamine neurons, providing susceptibility to repeated social defeat stress.

Analysis of neurotransmitters/neuromodulators released under low gravity using microdialysis technique

It has well known that potential for immunity in human body is decreased under a stress. While, macrophages (M s) play an important role for immunoresponse. Cytokines are also affected by a stressed condition. The specific alternation of rhythm in temperature (SART) stress is one kind of environmental stress, induced by repeated sudden changes in ambient temperature. The SART-stressed animals are vagotonia-type autonomic imbalance model and have chronic stress symptoms. Therefore, it is supposed that the relationship between the autonomic nervous system, the endocrine system and the immune system breaks down in SART-stressed animals. In this work, to clear the relationships between stress and natural immunity, we investigated the change for immunoresponce in SART stressed mice using as an indicator for the number and the activity of alveolar M s. Male ddY mice, weighing 20–30 g, were used. The bronchoalveolar lavage fluid (BALF) was obtained by washing lungs with phosphate-buffered saline under urethane anesthesia. Histological samples were prepared from mice lung after fixation by 4% paraformaldehyde perfusion. M fraction was obtained from the pellet by centrifugation of BALF. Number and phagocytotic activity of M s in stressed group were significantly decreased in comparison with those in unstressed and cold stressed group. The amounts of inflammatory cytokines, IL-1 , IL-6 and TNF, in BALF were significantly reduced in the SARTstressed group. We obtained the similar result in the culture medium of M s for 48 hours from the SART-stressed group, that is, the amounts of cytokines except IL-1 was reduced. Repeated oral administration of antianxiety drug, diazepam, attenuated the reduction of the number of M , phagocytotic activity and the amount of cytokines in BALF, which observed in the SART-stressed mice. These results suggest that the immune function in SART stressed mice under a repeated change in ambient temperature may be decreased.

Self-selection of anti-depressant herbal medicine depends on internal and external conditions in rats

the open arms in the EPM was negatively correlated with food intake during recovery period in the TPF-r. This result suggests that the rat showing higher anxiety could consume more food after mild stress. Though the significant difference was not observed in the locomotor activity among the TPF-r, TP, and CF, the TPF-n showed shorter distance moved in the open field after the tail pinch compared to the other groups. This result implies that the expression of eating in stress condition could affect consecutive behaviors. Research fund: Grant-in-Aid for JSPS Fellows (22.6878).

The mere presence of partner attenuates freezing response but not avoidance behavior in learned avoidance paradigm in rats

Previous neuroeconomics studies have demonstrated that several neuropeptides and steroid hormones are associated with trust and reciprocity (Zak et al., 2005; Kosfeld et al., 2005; Takahashi et al., 2005). So far, no study to date examined whether sex hormones determine participants’ tendencies for trust and reciprocity in the distant future (e.g. over a year later). The purpose of this study is to examine the relationships between sex hormones (e.g., testosterone and DHEA) and decisions in the trust game conducted 18 months later in adult men and women. A total of 92 adults participated in the study whose salivary testosterone and DHEA levels were assessed by utilizing liquid chromatography/mass spectroscopy (LC/MS). Eighteen months later, the participants played a trust game which assessed tendencies for trust and reciprocity. Our results showed that testosterone had a strong negative effect on reciprocity but not on trust, even when controlling for the effect of age and sex were. DHEA had no effect on either trust or reciprocity. These results suggest that testosterone determines long-term (over a year) tendencies to engage in reciprocity. Research fund: Grant-in-Aid for Scientific Research on Priority Areas (19046005).

Low dose neonatal exposure to bisphenol A affects emotional and social functions in a sex dependent manner in rats

P3-o18 Behavioral role of thalamostriatal neural pathway in conditional discrimination paradigm Shigeki Kato 1 , Masahito Kuramochi 1,2, Kenta Kobayashi 1, Ryoji Fukabori 1, Motokazu Uchigashima 3, Masahiko Watanabe 3, Yuji Tsutsui 4, Kazuto Kobayashi 1,2 1 Dept. Mol. Genet., Fukushima Med. Univ., Fukushima, Japan 2 CREST/JST, Kawaguchi, Japan 3 Dept. Anat., Hokkaido Univ., Sapporo, Japan 4 Div. Human Support Sys., Fukushima Univ., Fukushima, Japan

Social interaction modulated by nasal application of testosterone in the rhesus monkey

Areas in and around superior temporal sulcus (STS) are thought to be important to social behavior (e.g., recognizing other’s action and intention). Although new-world monkey marmosets have strong pro-social nature, data related connection of STS is scanty. We performed retrograde tracer (CTB-Alexa 488 or 555) injection around superior temporal cortex of the marmosets. So far, we have made three injections into dorsal and ventral parts of middle STS and dorsal part of caudal STS. We found each injection resulted in unique input pattern, like macaque monkey (Selzer and Pandya, 1994). But, in general, areas around STS receive strong projection form multiple sources (insular, parietal cortex, frontal and occipital cortices), as expected as its multi-modal nature. Based on these results, we will discuss the subdivision of the marmoset areas around STS, by combining with electrophysiology and cytoarchitectures. Research fund: KAKENHI (22300104).

Acquisition and Extinction of Avoidance Response by Social Interaction in Rats

In rodents, many forms of behavior (avoidance, food choice, exploring, etc.) have been shown to be transmitted through social interaction. Previous psychological studies have shown that acquisition of avoidance behavior is under the influence of social interaction but detail analyses have not been done. In the present study, we studied how learned avoidance behavior is influenced by interacting with other rats which have different experiences to foot shock using passive avoidance paradigm. Rats received electrical shocks in the dark compartment and avoided entering there were used as subjects. In Experiment 1, the latency to enter the dark compartment was measured under three different conditions; without any partner (ALONE), with a shock-received partner (wSHOCK) and with a unshocked-naive partner (wNAIVE). The latencies of wSHOCK and wNAIVE to enter the dark compartment were shorter than that of ALONE. In Experiment 2, the effects of other rats’ behavior on reinstate of avoidance were examined. The subject rats used in the Experiment I were put in the dark compartment without electrical foot shock and habituated to the compartment. Then the latencies to enter the dark compartment were measured in absence or presence of demonstrator rat which received electric foot shock in front of the subject rats. The demonstration of receiving foot shock by other rats enhanced avoidance responses. These results suggest that learned avoidance may be modified by partners’ behaviors in reciprocal fashion.

Involvement of nucleus accumbens dopamine in feeding and affective behaviors in rats

The amygdala and serotonergic innervation thereonto are considered to cooperatively regulate emotional states and behaviors. In the present experiments, we investigated how the serotonergic input modulates the excitability of lateral amygdala (LA) neurons by whole cell recordings and voltage-sensitive dye imaging in rat brain slices. Bath-application of serotonin (5-HT) induced a slow afterdepolarization (sADP) in LA neurons. This sADP lasted for more than 5 s. This sADP was also induced by synaptic stimulations. These results suggest that 5-HT enhances the excitability of amygdala neurons by inducing sADP. On the other hand, by using voltage imaging, we observed that bath-application of 5-HT suppressed the excitatory synaptic propagation from LA to endopiriform nucleus, perirhinal cortex, piriform cortex and basolateral amygdala. The suppression by 5-HT was also observed in patch clamp recording from the neurons in endopiriform nucleus and basolateral amygdala. Taken together, it is suggested that 5-HT has two opposite effects, enhancing the excitability of LA and suppressing the synaptic propagation from LA.

Spiecies-, sex- and time-dependent neurobehavioral effects of bisphenol A

O3-I4-4 CaM kinase II activation is essential for cognitive function through Na+/Ca2+ exchanger type 2 Shigeki Moriguchi1, Feng Han1, Norifumi Shioda1, Satomi Kita2, Issei Komuro3, Takahiro Iwamoto2, Kohji Fukunaga1 1 Department Pharmacol., Grad. Sch. Pharm. Sci., Tohoku University, Japan; 2 Department Pharmacol., Sch. Med., Fukuoka University, Japan; 3 Department Cardiovasc. Sci. Med., Grad. Sch. Med., Chiba University, Japan