Effects Of Dopamine D2 Receptor And Its Related Neurotransmitters And Receptors On Behavior Regulation Of Brown Voles In

Emotions are human and animal’response phenotypes to objective stimulation, which mainly consist of subjective psychological experience and physiological performance. Emotion can also alter behavioral phenotypes including social and nonsocial behavior under disturbance induced by different external factors. So it is significant to investigate how different early social environments affect animal’ emotions and related social and no-social behavior, as well as the neurophysiological mechanism in regulating emotion and behavior using monogamous mandarin vole with high levels of sociability.The amygdala is a critical area of limbic subcortex, having extensive connection with the cerebral cortex, hippocampus, cingulate gyrus and hypothalamus. It is also one of the integration center of varieties of sensory information, which play an important role in regulating emotion and behavior. Previous studies demonstrate that more complex social relationship, more frequent social communication are associated with more active and large amygdala. The lesion of the amygdala reduces the anxiety-like and social behaviors, including aggressive and amicable behavior. Thus, the relationships among the amygdala, emotional behavior and social behavior have attracted more attention.The amygdala is closely connected with mesolimbic dopaminergic system in the regulation of fear and anxiety. In addition, it is found that dopamine D1and D2receptors distribute in the amygdala, and many studies have also suggested the role of D1receptor in the regulation of emotional behavior, whereas the function and the underlying mechanism of D2receptor in the amygdala in regulating emotional behavior remains unclear. The amygdala has vasopressin neurons and receives the projections of vasopressin and oxytocin, as well as regulates the release of AVP (Arginine vasopressin) and OT(oxytocin) in the hypothalamus. The vasopressin receptor in the amygdala belongs to AVPV1α receptor and is involved in the regulation of social behaviors, such as emotion behavior, social investigation, sexual behavior, aggressive behavior, and amicable behavior. In other brain regions, DA has been involved in regulating the level of AVP and OT. However, the role of D2receptor in the amygdala and the relationship with AVP, OT and their receptors in the regulation of animals emotional behavior and social behavior remains unclear, especially under specific social and environment stimulation. The present study would investigate the effects of environmental alteration, including early social environment and early experience, on animal emotion, social and nonsocial behavior using socially monogamous mandarin vole, Microtus mandarinus. In addition, the role of DA and D2receptor in the amygdala and their relationships with AVP, OT, AVPale and OTR were also investigated using the microinjection, neuropharmacological, immunohistochemical, microdialysis and RT-PCR techniques. The main results including the following points:1:In the open field test, the voles with injection of DA2R antagonist into the amygdala spent significantly more time in central area and had more transitions between quadrants (P<0.01) and total distance traveled(P<0.05) comparing with saline group. However, no significant difference was found between the D2R agonist and saline groups. In addition, no sexual differences were found on the parameter of the open field test.2:In the social interaction test, injection of DA2R antagonist in the amygdala significantly inhibited aggressive and escape behavior, but increased contact and exploration behaviors in female-male and female-female social interaction. Significant increased accepting behavior was also found in female-male social interaction.3:Injection of DA2R antagonist in the amygdala significantly increased the number of OT-ir neurons in the PVN(paraventricular nucleus) and SON(Supraoptic nucleus). The voles injected D2R agonist into the amygdala only had more number of AVP-ir neuron in the SON.4:The voles being injected D2R antagonist into the amygdala had higher levels of serum OT (P=0.001), but the serum concentration of AVP and CORT have not been changed by this treatment.5:The concentration of monoamine substrate in the amygdala induced by different social interactions measured using the micro-dialysis combining with HPLC (High Performance Liquid Chromatography)analysis:the results showed that the subjects showed increased attack and escape behavior, and decreased contact behavior towards unfamiliar same-sex individuals. In addition, there was a tendency to reduce investigating behavior. When the voles encounter with novel different-sex individuals, they exhibited increased attack behavior and escape behavior, and decreased contact behavior. A reduced tendency in investigating behavior was also found in this condition. The voles showed increased DA concentration in the amygdala during social interactions with novel same sex individuals, compared to basic levels (the voles stay alone). There was no change under the stimulation of familiar individual. Interaction with familiar and unfamiliar different-sex individuals also increased the levels of DA in the amygdala. The voles interacting respectively with same-sex and different-sex individuals both showed higher levels of DA concentration in the amygdala compared to those interacting with familiar voles. In addition, there was no significantly difference between the levels of DA concentration during same-sex and different-sex interaction. Increased NE concentrations were also found under the stimulation of familiar or unfamiliar individuals with different-sex compared to the basic level.6:The male mandarin voles respectively from the PD(paternal deprivation), ED(early deprivation), and CUMS(chronic unpredicted mild stress) groups showed significant reduced the percentage of time in central area in open field test compared to that of control group. PD, ED and CUMS group also displayed significantly less total transitions and moving duration in the open field.7:In the male-male and female-male social interaction test, PD significantly reduced aggressive, escape and contact behaviors, and increased the exploration behavior. The results of RT-PCR showed that significant differences were found in the levels of DA2R、OTR、AVPV1R mRNA expression except for DA1R. The levels of DA2R mRNA expression in the PD and ED groups were significantly higher than those of CUMS and control group. ED and CUMS significantly decreased OTR mRNA expression in the amygdala. There was no significant difference between the CUMS and control group in DA2R and OTR mRNA expression. The levels of AVP V1R mRNA expression in the PD group was significantly higher than the CUMS, ED and the control group.8:In the habituation-dishabituation paradigm, repeated measures ANOVA did not reveal significant interactions for trial-sex and trial-treatment-sex. However, significant interactions between trial and treatment were found and trials showed significant main effects. Compared to the control group, PD significantly reduced the levels of OTR mRNA expression in the MeA. Animals in the PD group failed to show any habituation and dishabituation behaviors, displaying impaired social recognition.The above results show that: 1:The alteration of social environment or chronic stress can lead to anxiety, and then to change the social behavior. There is closely correlation between emotional and social behavior alteration.2:In the amygdala, DA2R play an important role in regulating social behavior and emotional alteration. Its regulation may be related to the number of OT-ir neurons in the PVN and SON.3:There are significant differences in social behaviors during social interaction between individuals with different sexes or different familiarity in mandarin voles. These differences may be due to the change of DA and NE concentration in the amygdala. High levels of DA in the amygdala lead to more aggressive behavior and less contact behavior between two unfamiliar same sex individuals in male mandarin voles. And high levels of DA and NE is one of the factors resulting in more aggressive behavior and less contact behavior between two unfamiliar voles with different sex.4:The changes of emotion and related behaviors induced by different early social environment may be through the variation of different neurotransmitters and receptors in the amygdala. Paternal deprivation leads to elevated expression of DA2R and AVPV1R in the amygdala, and subsequently changes the social behavior and emotion in adulthood. The basic reason of reduced OTR in the amygdala and impaired social recognition may be the deficiency of paternal care toward their pups.