Electronic Cigarettes (ECs) are battery-powered nicotine delivery devices that have rapidly gained popularity amongst adolescents globally. Nicotine is the most toxic and addictive agent of ECs. Our published studies demonstrated that chronic nicotine exposure attenuates short-term synaptic plasticity and histamine metabolism thus causing severe ischemic stroke outcomes in female rats. Here, we hypothesize that chronic EC exposure alters histamine metabolism and synaptic proteins, thus altering cognition in the adolescent rats of both sexes. Rats (2-3 months old) of both sexes were exposed to either air or EC vapor (5% nicotine Juul pods) using the EcigAero-TM Aerosol Exposure Apparatus (between 7pm-7am; the active phase of circadian cycle) for 16 days. Per night, rats were exposed to 16 episodes of EC and each episode consisted of 2 second Juul puffs followed by 8 seconds of air respectively for 8 minutes. Rats were tested for learning and memory using a water maze for the last 7 days of EC exposure. Following behavioral testing, brain tissue was harvested for western blotting of synaptic proteins and metabolomic analysis (performed by Metabolon Inc.). The results of western blot analysis showed a significant decrease in vesicular proteins munc-18 and synaptotagmin in the EC-exposed rats. The metabolomics data revealed a significant decrease in histamine metabolism. We observed significantly increased latency in finding the hidden platform in EC-exposed rats, suggesting deficits in spatial learning. The observed changes may be responsible for cognitive decline and increased stroke severity due to nicotine exposure.
