Mechanism of Prenatal Cannabinoid Exposure Mediated Memory Loss in Adolescent Offspring: Opportunities for Identifying Therapeutic Target

Abstract

Cannabis use during pregnancy has increased by 62% from 2002 through 2014 and is now the most commonly used illicit drug during pregnancy, in part due to its ability to reduce morning sickness during pregnancy. Several studies have demonstrated that neural network activity which underlies typical cognitive and behavioral processes can be altered by prenatal cannabinoid exposure (PCE) leading to a long lasting effects on adult behavior. Here, we have investigated the impact of PCE in adolescent offspring in hippocampus dependent learning and memory via performing a series of behavioral, electrophysiological and immunochemical studies. An osmotic pump filled with either vehicle or the cannabinoid receptor full agonist WIN55, 212–2 (2 mg/kg body weight/day) was implanted subcutaneously in gestational day 4, which delivered the drug at a constant rate until the pups were born. Contextual Fear Conditioning and Morris Water Maze test were performed to investigate the hippocampus based memory revealing significant learning deficits in the PCE group. To investigate the mechanisms behind observed behavioral deficits, electrophysiological experiments were performed on acute hippocampal slices. Reduced long‐term potentiation and enhanced and long term depression were observed in the PCE group demonstrating impaired synaptic plasticity. To identify alterations in the downstream signaling cascade involved in glutamatergic neurotransmission, immunoblotting experiment was performed. Immunoblotting data showed increased Cannabinoid Receptor Type 1(CB1) expression along with reduced Neural Cell Adhesion Molecule (NCAM) expression. NCAM is important for maintaining proper neuronal connections, and it modulates NMDA mediated glutamatergic neurotransmission. Based on our data, we hypothesize that a reduction in NCAM may be responsible for the learning and memory deficits observed in PCE animals and can be used as a therapeutic target to ameliorate the cognitive deficits in PCE offspring.Support or Funding InformationNo Available Funding SourceThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.