100: Effects of lactation on susceptibility to opioid dependence in the chemically-naive subject

Abstract

Prescription and illicit opioid misuse, overdose, and the development of opioid use disorder (OUD) are pressing problems globally. This class of drugs acts through opioid receptors expressed within the corticostriatal circuitry underlying reward processing. For many women, their first exposure to opioids is following childbirth. Oxytocin has also been shown to have a role in reward processes. We investigated the hypothesis that lactation in female mice impacts brain expression of OPRs and related proteins. After delivery female B629SF2/J mice were randomized into lactated (L, n=10-16) and non-lactated (NL, n=10-12) groups. In the L group, dams breastfed their pups until they were 21 days old. In the NL group, the dams were separated from their pups within 24 hours of birth. Dams were sacrificed at 6 months postpartum and their brain cortex isolated. Expression of the following genes involved in neural pathways which are implicated in the development of OUD was determined using quantitative real time RT-PCR: brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), mu-opioid receptor (OPRM1), delta-opioid receptor (OPRD1), proenkephalin (PENK), and tyrosine hydroxylase (TH). GAPDH was used as control. Statistical analyses were performed using Student t or Mann-Whitney tests as appropriate (statistical significance P < .05). The OPRM1 receptor levels were significantly lower in L compared to NL dams (P=0.03, Fig). Elevated levels of OPRM1 have been found in chronic substance abusers and in those in craving states for substances of abuse. OPRD1 levels were significantly higher in L compared to NL mice (P=0.02, Fig). OPRD1 receptors have been associated with inhibition of impulsivity. The higher levels of OPRD1 found in L dams may imply a lesser susceptibility to the effects of substances of abuse. No other differences were found. By decreasing OPRM1 levels and increasing OPRD1 levels in the cortex, lactation may have a long-lasting protective effect against the development of OUD. Additional studies to determine the mechanisms for this protective effect and the role of oxytocin signaling are warranted.