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

Abstract

175 words Main text: 3871 words Figures: 4 main, 5 tables AbstractCannabis is the world's most widely abused illicit drug and consumption amongst women during and surrounding the period of pregnancy is increasing. Previously, we have shown that cannabinoid exposure via lactation during the early postnatal period disrupts early developmental trajectories of prefrontal cortex maturation and induces behavioral abnormalities during the first weeks of life in male and female rat progeny. Here, we investigated the lasting consequences of this postnatal cannabinoid exposure on synaptic and behavioral parameters in the adult offspring of ∆9-tetrahydrocannabinol (THC)-treated dams. At adulthood, these perinatally THC-exposed rats exhibits deficits in social discrimination accompanied by an overall augmentation of social exploratory behavior. These behavioral alterations were further correlated with multiple abnormalities in synaptic plasticity in the prefrontal cortex, including lost endocannabinoid-mediated long-term depression (LTD), lost long-term potentiation and augmented mGlu2/3-LTD. Finally, basic parameters of intrinsic excitability at prefrontal cortex pyramidal neurons were similarly altered by the perinatal THC exposure. Thus, perinatal THC exposure via lactation induces lasting deficits in behavior and synaptic function which persist into adulthood life in male and female progeny.

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

“…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).…”

“…The magnitude of plasticity was calculated at 0-10min and 30-40 min after induction (for TBS-LTP and eCB-LTD) or drug application (mGlu2/3-LTD) as percentage of baseline responses (Scheyer et al, 2020a). Statistical analysis of data was performed with Prism (GraphPad Software) using tests indicated in the main text after outlier subtraction (Grubb's test, alpha level 0.05).…”

“…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.…”

“…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). The data demonstrate that rats exposed during lactation to WIN display social, cognitive and motivational deficits at adulthood.…”

“…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).…”