Maternal cannabinoid exposure during lactation alters the developmental trajectory of prefrontal cortex GABA-currents in offspring

Abstract

Cannabis is the most widely used illicit drug in the world, and its usage is increasing with its widespread legalization. Use of the drug by mothers during lactation may transfer active cannabinoids to the developing offspring, altering postnatal neurodevelopment during this critical period. During early life, GABA undergoes a functional switch from an excitatory to an inhibitory neurotransmitter due to reciprocal changes in expression of the K+/Cl- co-transporters KCC2 and NKCC1. Here, we characterize the functional GABA switch in the prefrontal cortex of both male and female rats. We show that treating rat dams with {Delta}9-THC or a synthetic cannabinoid during early lactation (PND01-10) retards KCC2 expression and delays the GABA switch in pups of both sexes via a CB1R-dependent mechanism. Our results indicate that the developmental trajectory of GABA in PFC neurons is significantly altered by perinatal exposure to cannabinoids through lactation during the early perinatal period.