Effects Of Early Cocaine Exposure On Behavioral And Neuroendocrine In Adolescent And Adult Mice

Cocaine is the commonly utilized drug in drug abuser. The effects of prenatal or neonatal cocaine exposure has attracted considerable attention, and has been well documented in developmental and behavioral outcomes. However, little is known about specific neurochemical mechanisms on early treatment as a model, and whether there are sex-specific differences in these effects. The two well-known neuropeptides,arginine vasopressin(AVP) and oxytocin(OT) play a pivotal role in reward and stress systems Furthermore, they regulate social behaviors and are involved in drug abuse.Here, we firstly investigated the effects of neonatal cocaine exposure prior to weaning on behavioral and AVP, OT, corticosterone(CORT) and neuronal activations when mice reached adolescence and adulthood. Second, we assessed acute cocaine-induced behavioral sensitization in juveniles following neonatal cocaine exposure.In experiment 1, female and male ICR mice were given 20 mg of cocaine /kg body weight, intraperitoneally(in one daily doses), from postnatal day(PND) 5 to PND21, and were evaluated on middle adolescence(PND30) and adults(PND65).Controls were given 0.9% saline. Locomotion, anxiety levels and social behaviors were examined using an open field test and the same–sex social interaction test. The concentration of serum AVP, OT and CORT were measured using ELISA. AVP-, OTand c-Fos- immunoreactive(IR) neurons were measured using Immunohistochemistry.The results showed that neonatal cocaine exposure had no effect on locomotion on adolescents and young adults; however, rearing behavior or self-grooming behavior increased in these phases. As well, neonatal exposure reduced anxiety levels in adolescent males. Furthermore, neonatal cocaine exposure affect few social behavior based on the assessments used in this study, in contrast, more social behaviors were altered in young adults. Along with these changes, neonatal cocaine exposure aggravated the levels of serum CORT in both sexes, while the expression of AVP-IR and OT-IR neurons in the paraventricular nucleus(PVN), supraoptic nucleus(SON)and the levels of serum AVP and OT were changed in sex-specific and age-dependentstyle. c-Fos-IR neurons exhibited differential activations or inactivation within specific reward areas, such as PVN, SON, bed nucleus of the stria terminalis(BNST),central nucleus of the amygdala(CeA), the ventral pallidum(VP), posterior cingulate cortex(PCg). Furthermore, these effects were not consistent across age and gender.In experiment 2, we examined the locomotion and anxiety levels of PND45 mice to acute cocaine treatment(20mg/kg, in two daily doses) following neonatal cocaine exposure prior to weaning. Compared to controls, cocaine-exposed females experienced an increase in the locomotion, whereas anxiety levels were not altered. In contrast, the change of locomotion was not found in males.These results indicate effects of neonatal cocaine exposure on behavioral and neuroendocrine responses were not consistent in adolescents and adults. Furthermore,the neonatal cocaine-exposed females may be more sensitive to acute cocaine than females. The differential expression of OT and AVP and the abnormity of neurons activations are likely to play an important role in mediating the alteration in social behavior or cocaine-induced behavioral sensitization.