Differences In The Attachment Of Cottage And The Dependence Of Cocaine And The Influence On The Cocaine Effect On The Offspring Of The Brown Voles And The Related Mechanism Of The Internal Nervous System

Social attachments are essential for maintaining human mental health. Using animal models, it is found that positive social interactions reduce stress and anxiety and effectively inhibited drug abuse. Therefore, social attachments are closely associated with effects of drug abuse. Social bonding includes formation of attachments to offspring, mates and peers. So far, the studies examining such reciprocal interaction have mainly focused on the pair bonding or mother-offspring bonding, however, little is known about interaction between father-offspring bonding and drug abuse. As well as in human, the father-offspring bonding also exist in many monogamous species (e g. Prairie vole, Mandarin vole). Moreover, father and offspring provide social rewarding mutually. Father play a vital role in the growth of children, in return, the influence of children to father also should not been ignored. Oxytocin (OT) and vasopressin (AVP) have been found to regulate close social attachment and enhances the reward value via activating or mediating dopaminergic (DA) reward circuits. We established the monogamous mandarin vole (Microtus mandarinus) as a model to investigate two parts: one hand, through conditioned place preference (CPP) tests to establish two different rewards including the natural reward of pups to father and drug reward, we aim to find possible difference between natural reward and drug reward in related neurochemical substrate. On the other hand, through neonatal paternal deprivation treatment and administration of cocaine in adolescence, we investigate possible different sensitivity to addictive drug under two different growing experiences.1. Comparison of the expression of central oxytocin receptor (OTR), dopamine D2 receptor (D2R), vasopressin receptor (V1aR) and the concentration of serum oxytocin (OT), vasopressin (AVP), estradiol (E2), testosterone (T) in pup reward and drug reward.CPP test:we found father preferred the cues associated with pups and the cues associated with cocaine. This indicated both pups and cocaine could elicit high value reward and it was success to establish two different rewards.The expression of OTR, D2R, VlaR:we found two different rewards induced the same change trend in the expression of OTR, D2R, V1aR. Two different rewards had higher level expression of OTR in the medial amyglada (MeA) and lower level of D2R, V1aR expression in the nucleus accumbens (NAcc) compare to those of control group. However, the changes of OTR in the Me A and V1aR in NAcc induced by pups reward were more significant than the cocaine-induced changes.Elisa:we found two different rewards induced different change in the serum concentration of associated hormone. Only pups reward significant increased the concentration of OT and E2. Cocaine reward decreased the concentration of AVP but pups reward induced the opposite change. Both pups and drug rewards significantly reduced serum T.2. Comparison of behaviors, central oxytocin and serum oxytocin and estradiol levels between PC and PD mandarin voles under the condition of acute cocaine treatment.Open field test:we found PD had a main effect on time spent in the central area and cocaine had a main effect on the distance of transitions. Cocaine reduced the percentage of time in the center of area only in the PC group. However, cocaine increased the mobile distance in the PD group.Social interaction test:we found that PD females engaged in less social contact behavior and more inactivity behavior when interacting with same-sex individuals. Cocaine treatment decreased the duration and frequency of contact and increased the duration and frequency of inactivity only in the PC group.Numbers of oxytocin-immunoreactivity (OT-ir) neurons:we found PD induced a decline in the expression of OT in the paraventricular nuclei of the hypothalamus (PVN) and supraoptic nuclei of the hypothalamus (SON). Cocaine also induced a decline in the number of OT-ir neurons in PVN and SON but only in the PC group.Elisa:we found both PD and cocaine significantly affected the concentration of serum estradiol (E2) and OT. Cocaine-treated females had lower levels of E2 and OT in PC and PD groups. As well as the effect caused by cocaine, PD decreased the concentration of E2 and OT only under saline-treated condition.In conclusion, our work demonstrated that pups can produce a reward effect to the father and this natural reward may be different from drug reward, at least on the change scope of OTR and V1aR. Similarly, fathers also play an important role to offspring because paternal absence can induce ’floor effect’ of cocaine. Paternal absence would lead to a series of accumulating negative changes that make the individual more anxiety, less socially.