Impaired Synaptic Plasticity in the mPFC and Anxiety-Like Behaviour in Rats Following Repeated Nitrous Oxide Exposure

Nitrous oxide (N2O), also called laughing gas, is used and abused recreationally worldwide. It has been found that long-term N2O abuse impairs the central nervous system in humans, including the prefrontal cortex (PFC), which is a critical brain region involved in cognition. However, there is no ideal rodent model of laughing gas abuse. In the present study, we tested the impact of N2O inhalation 12 h following its delivery on the behavioural responses of rats and the synaptic transmission properties of the medial prefrontal cortex (mPFC). We found that short-term (1 h/day for 1 day) inhalation of 40% N2O had no significant effect on the performance of rats in the elevated plus maze test, light–dark transition test, tail suspension test, forced swim test, novel object recognition test, and social recognition test. However, long-term (1 h/day for 10 days) inhalation of 40% N2O induced anxiety-like behaviour in the elevated plus maze test and light-dark transition test, but no abnormal performance was observed in the other four behavioural tests. In addition, long-term N2O inhalation impaired long-term potentiation, but not basal synaptic transmission or the paired-pulse ratio, in the mPFC. These results demonstrate that long-term repeated N2O inhalation induces anxiety-like behaviour and impairs synaptic plasticity in the mPFC of rats.