Perinatal THC exposure via lactation induces lasting alterations to social behavior and prefrontal cortex function in rats at adulthood

Neuropsychopharmacology (2020) Cite this article

Abstract: Cannabis 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.

Discussion: Here, we have discovered that perinatal exposure to THC via lactation induces significant behavioral and electrophysiological alterations lasting into adulthood. Specifically, we found that this THC exposure alters social behavior, as well as synaptic plasticity and basic parameters of cell-excitability in the PFC of adult male and female offspring of dams given THC during the first 10 days of postnatal life.

…Our results indicate that perinatal THC exposure via lactation induces lasting deficits at multiple scales which persist into adulthood. THC-exposed offspring exhibit increased social exploration at the cost of discrimination, coupled with significant alterations to multiple forms of plasticity in the PFC which are normalized via enhanced basal 2-AG ex vivo. Increased excitability of principal neurons of the PFC may underlie or accompany these issues, and further investigations are required to further characterize the extent to which basic synaptic transmission may be impacted by this early life exposure. Further, both an increased breadth of behavioral investigations as well as extended characterizations of plasticity and synaptic functions in these animals in other brain regions are necessary to provide a more thorough picture of the extent to which perinatal cannabis exposure induces lasting deficits in brain function into adulthood.

For complete study go to https://www.nature.com/articles/s41386-020-0716-x