Cannabinoid Exposure via Lactation in Rats Disrupts Perinatal Programming of the Gamma-Aminobutyric Acid Trajectory and Select Early-Life Behaviors

Abstract

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Perinatal THC Exposure via Lactation Induces Lasting Alterations to Social Behavior and Prefrontal Cortex Function in Rats at Adulthood

“…In rodent models, exposure to cannabinoids (both synthetic and plant-derived) during gestation or early development induces an array of deleterious consequences on behavior manifesting both at early life and adulthood 20,[26][27][28]34,35 . Previously, we have shown that the administration of cannabinoids to lactating dams during the early postnatal period causes significant delays in both synaptic and behavioral development 28 . Here, we used the same protocol of perinatal cannabinoid exposure in order to determine if such early-life exposure results in consequences lasting into adulthood.…”

“…During the early postnatal period, we have shown that exposure to exogenous cannabinoids via lactation also alters the developmental trajectory of the PFC 28 . Specifically, the timeline of cell excitability changes mediated by GABAergic maturation is delayed by exposure to either THC or a synthetic agonist of CB1R.…”

Maternal exposure to the cannabinoid agonist WIN 55,12,2 during lactation induces lasting behavioral and synaptic alterations in the rat adult offspring of both sexes

“…We have previously shown that exposure to cannabinoids via lactation alters the developmental trajectory of the prefrontal cortex (PFC), which has been identified as a cortical hub essential to planning, cognitive flexibility and emotional behaviors (Goldman-Rakic, 1990) and a common target in various endocannabinoid-related synaptopathies (Araque et al, 2017). Our work revealed that exposure of lactating females to either THC, or a synthetic agonist of CB1R, altered the maturational trajectory of GABAergic transmission and led to behavioral abnormalities in early life (Scheyer et al, 2020b). Very recently, we reported that perinatal THC exposure via lactation elicited lasting, deleterious impacts on social behavior and synaptic plasticity in the PFC of the adult offspring (Scheyer et al, 2020a).…”

“…Cannabis consumption by pregnant women is progressively increasing 1-4. The principle psychoactive component of cannabis, ∆ 9-tetrahydrocannabinol (THC), in addition to other cannabinoids, is actively transferred to the developing infant via breastfeeding (Hurd et al, 2019;Scheyer et al, 2019Scheyer et al, , 2020aScheyer et al, , 2020b. During the perinatal period (i.e.…”

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Consumption of cannabis during pregnancy and the lactation period is a rising public health concern (Scheyer et al, 2019). We have previously shown that exposure to synthetic or plant-derived cannabinoids via lactation disrupts perinatal programming of the gamma-aminobutyric acid trajectory in the prefrontal cortex and early-life behaviors (Scheyer et al, 2020b). Recently, we described lasting behavioral and neuronal consequences of ∆ 9-tetrahydrocannabinol (THC) perinatal exposure via lactation (Scheyer et al, 2020a).Here, we extend upon these findings by testing the effects in offspring of maternal exposure to the synthetic cannabinoid agonist WIN 55,12,2 (WIN).

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