Does Methamphetamine Abuse Affect Serotonin Signaling in the Maternal-Placental-Fetal System?

Abstract

Although methamphetamine (METH) is the most commonly abused drug during pregnancy, there is surprisingly little data on METH effects on gestational tissues. This study, building on our recent research describing the effects of METH on antioxidant status and catecholamine signaling in gestational tissues, assesses serotonin levels in the umbilical cord during pregnancy and effects of demographics and neonatal variables. We hypothesized that METH ingestion and/or smoking may alter serotonin signaling in the umbilical cord. Umbilical cords (n = 85) were collected, processed to total lysates and standardized to 2 mg/mL protein. Serotonin levels were determined by ELISA then correlated to different demographic and pregnancy variables, antioxidant and catecholamine levels then the effects of METH and/or smoking determined. Levels of serotonin in umbilical cords were not significantly different between METH users nor smokers and control cords. Additionally, there were no significant correlations with delivery type, parity, gravidity neonatal baby weight, or maternal age. Serotonin levels were positively correlated with maternal diabetes (P=0.04) and negatively correlated with Gestational age (P = 0.05, r = 0.2310) and placental weight (P = 0.04, r = -0.3527). Serotonin levels may also be affected by maternal hypertension (P = 0.06) as well as preeclampsia (P = 0.08). While umbilical serotonin was not related to levels of noradrenaline and dopamine nor to the antioxidant enzymes glutathione-S-transferase, catalase, super-oxide dismuatse or xanthine oxidase levels; serotonin increased as thioredoxin reductase (TRX, P = 0.0003, r = 0.40) and glutathione peroxidase (GPx, P = 0. 01, r = 0.28) activities increased. A potential association between serotonin and with Vitamin C levels was also noted (P = 0.07, r = 0.2942). When stratified for METH and smoking, patients with diabetes showed that umbilical serotonin may be further lowered by smoking but not METH (P = 0.06 non smokers vs. smokers, P = 0.08 smokers vs. Meth+smokers). Furthermore, THC caused a significantly higher gravida (P = 0.01) than non-smokers. When stratified, smokers showed a significantly higher chance in getting pregnant than those that do not smoke (P=0.0002). Those that smoke in addition to THC, however, have a significantly lower chance of getting pregnant than those that only smoke (P=0.0173). THC also suggestively causes a lower neonatal baby weight (P = 0.02). Whilst THC did not show any significant differences in CAT levels with respect to different types of smokers, those who smoke THC have significantly higher levels of Vitamin C (P = 0.0383) ,a significantly lower level of GPx activity than those who do not smoke (P =0.05) and a significantly higher level fof noradrenaline (P = 0.02). Serotonin signaling in umbilical cords is affected by hypertension and diabetes as well as oxidative stress, which may itself be caused by the two clinical syndromes.