| Maternal behavior is the main component of parental care,including all the activities that females to protect and care for their offspring or the offspring of their relatives.Favorable maternal behavior can improve the survival rate of offspring,which is of great significance to the continuation and development of species and the stability of population.The initiation of maternal behavior requires the drive of maternal motivation,accompanied by the decrease of anxiety level.The normal expression of maternal behavior requires the regulation of emotion and motivation mainly in amygdala(Amy),medial preoptic area(MPOA),ventral bed nucleus of stria terminalis(BSTV),as well as dopamine(DA),5-hydroxytryptamine(5-HT),gamma aminobutyric acid(GABA)and other neuroendocrine systems.The coordination of maternal motivation and emotional regulation plays an important role in the expression of maternal behavior.The coordination process is also dynamically malleable and is influenced by many factors,such as maternal homeostasis and environmental conditions.Once the maternal adaptation during pregnancy and postpartum period is affected,it is easy to lead to postpartum mental disorders and maternal behavior damage.In rodent studies,the effects and mechanisms of the coordination between emotional regulation and maternal motivation on the expression of maternal behavior are rarely explored comprehensively,and the results of previous studies are still controversial or inadequate.First,the lack of a comprehensive study of "the effects of emotion and maternal motivation on maternal behavior" in rodents is partly related to the limitations of unitary methods for emotion and maternal behavior.The research methods of maternal behavior are mainly observational,and maternal anxiety was usually measured by elevated plus maze,open field and light dark conflict experiments.However,no single test paradigm has been used to explore postpartum anxiety and maternal motivation response in postpartum rats during tasks.Secondly,in the existing studies,drugs and stress are important factors affecting maternal behavior,but there are still many contradictions and problems unclear in the influencing results and mechanisms.On the one hand,psychotropic drugs regulating neurotransmitters are often used clinically to improve and treat postpartum mental disorders,and maternal behavior is also affected by these drugs.Some studies have shown that typical antipsychotics,which regulate DA system as a treatment,can disrupt maternal behavior by affecting maternal motivation and sedation.But does it also disrupt maternal behavior because it affects maternal anxiety? It's not clear.In addition,selective serotonin reuptake inhibitors can alleviate depressive symptoms by affecting 5-HT nerve conduction,and benzodiazepines can achieve antianxiety effect by inhibiting GABA.However,there are few studies on the effects of these two kinds of drugs on maternal motivation and maternal behavior,and the results are controversial,and the behavioral mechanism is not clear.On the other hand,maternal stress from pregnancy to lactation is also an important factor affecting maternal behavior.By reviewing the literature,we found that the influence of maternal stress on maternal behavior in rats was seriously dependent on the stress methods.The difference and mechanism of different stress methods need to be further studied.Therefore,this study focused on the theme of "the influence of anxiety and maternal motivation on maternal behavior ",and adopted the integrated maternal behavior research paradigm to explore the changes of postpartum anxiety and maternal motivation mediated by psychotherapy drugs and maternal stress,as well as the effects and neural mechanism on maternal behavior.In the first study,a new maternal behavior research paradigm was established based on the elevated plus maze(EPM)in primiparous lactating and nulliparous female rats.The effectiveness of this paradigm in detecting anxiety-like behavior and maternal motivation was preliminarily evaluated.First of all,according to the characteristics of postpartum female rats with lower anxiety level than non-pregnant rats,we detected lower anxiety level of postpartum female rats in the EPM tested with erasers(Experiment 1).The results showed that the ratio of open arms was a sensitive parameter of anxiety level.Secondly,in the pup's presentation condition of EPM(Experiment 2),the presence of pups significantly activated maternal motivation.The results showed that the mean speed,the number of retrieved pups and the number of closed arms entry well reflected the maternal motivation,and the mean speed was highly sensitive.In addition,by tracking and measuring the changes of anxiety and maternal motivation of female rats with different reproductive status over time,it was found that the low anxiety level of lactating rats remained stable;maternal motivation was higher only when pups presented,but with the repeated test,maternal motivation decreased.However,anxiety-like behavior of the nulliparous female rats decreased with the increase of repeated trials,and a few "sensitization" appeared in the later stage of the test.In the second study,using the paradigm of pup-based elevated plus maze by behavioral pharmacology method,investigates the effect and neural pharmacological mechanism of three commonly used antipsychotics,antidepressants and anti-anxiety drugs(Experiment 3: haloperidol,a dopamine D2 receptor antagonist;Experiment 4: fluoxetine,a selective serotonin reuptake inhibitor;and 5: diazepam,a GABA benzodiazepine receptor agonist)on postpartum anxiety and maternal motivation,further verify verified the effects of dopamine D2 receptor,serotonin system and GABA benzodiazepine receptors on maternal behavior.The results showed that:(1)dopamine D2 receptor plays a role in maternal behavior mainly through influencing maternal motivation rather than anxiety.(2)5-HT system also affects maternal behavior mainly through maternal motivation.(3)The role of GABA benzodiazepines receptors in maternal motivation and anxiety was not detected in this study,which may be the ceiling effect induced by the low anxiety level in our lactating rats.In the third study,maternal stress was used to explore the effects of anxiety and maternal motivation on maternal behavior and its neuroanatomical mechanism.In Experiment 6,maternal separation and forced swimming were conducted in postpartum rats,and then the behaviors of dams in the pup-based EPM,open field test,home cage maternal behavior and forced swimming test,and the effects of different stress modes on anxiety and maternal motivation were discussed.In Experiment 7,the expression of c-fos protein in amygdala(including central nucleus CEA and basolateral nucleus BLA),medial preoptic area(MPOA)and ventral tegmental area(VTA)was detected by fluorescence immunohistochemistry,and the effects of different stress modes on the activities of above-mentioned brain regions in the regulatory circuits of anxiety and maternal motivation were further explored.The main results are as follows:(1)maternal separation promotes the reduction of anxiety-like behavior,which is related to the activation of the Ce A in maternal brain,but has no significant effect on maternal motivation.The maternal motivation related brain regions(MPOA and VTA)have no significant effect.However the activation of Ce A promotes inhibition process of maternal behavior causes the disturbance in dams' nesting building behavior;(2)single forced swimming stress increased anxiety in dams.The inhibition of Ce A activity may be involved in the regulation of this process.VTA activity has also decreased.Inhibition of these two brain regions would have opposite effects on maternal behavior,respectively.Competition and coordination between the two regions would lead to no significant influence on maternal motivation and maternal behavior.(3)The dual stress of maternal separation combined with single forced swim reduced the anxiety of dams in the presence of pups,while no significant effect in the absence of pups.This result reflected the dynamic balance of the influence of the two kinds of stress on anxiety and the positive effect of pups' stimulation on the regulation of postpartum anxiety.(4)Repeated forced swimming had no significant effect on anxiety,and no significant changes were detected in the two subregions of amygdala(Ce A and BLA),but it enhanced maternal motivation,thus promoting nest building behavior of lactating rats.To sum up,this study investigates a novel paradigm of pup-based EPM on maternal behavior research,and applied this paradigm to explore the changes of anxiety and maternal motivation induced by DA,5-HT and GABA neurotransmitters and maternal stress,as well as their effects on maternal behavior and neural mechanism.The conclusions are as follows:(1)maternal motivation plays a leading role in the performance of maternal behavior,which is influenced by the stimulation information of pups.Postpartum anxiety plays a regulating role in the expression of maternal behavior,and a moderate level of anxiety is conducive to the performance of maternal behavior.(2)Dopamine D2 receptor system and 5-hydroxytryptamine system mainly affect maternal behavior by regulating maternal motivation.(3)The central amygdala(Ce A)is involved in the regulation of stress-induced anxiety,as well as in the inhibition process of maternal behavior.The ventral tegmental area(VTA)is involved in the regulation of maternal motivation influenced by stress.The result of competition and coordination between the two regions are related to the final performance of maternal behavior.The main innovations of this study are as follows:(1)the effects of anxiety and maternal motivation on the final expression of maternal behavior and their neural basis are comprehensively discussed from a new perspective of the coordinating role.(2)The same test method was used to compare the different effects of different stress on maternal anxiety and maternal motivation and the impact of their coordination on maternal behavior,which was helpful to clarify the inconsistencies in existing research results.(3)An integrated paradigm for the study of maternal behavior in a pup-based elevated plus maze was established and its effectiveness in detecting both anxiety and maternal motivation in female rats was investigated.This study has positive theoretical and practical significance.This study further enriched and improved the research theory of influencing factors of maternal behavior,which was conducive to a deeper understanding of the external performance of the interaction and coordination process between emotional regulation and maternal motivation,as well as the underlying mechanism of neurotransmitter and neuro circuits.The paradigm of pup-based elevated plus maze has further expanded the research paradigm of maternal behavior in terms of technical methods.The study on the influence of psychotropic medication and maternal stress on maternal behavior provides a reference for the treatment and intervention of postpartum mental disorders. |
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