Repeated Inhalation of Liquefied Petroleum Gas Inhibited the Expression of Dopamine D2 Receptor, Along With Pulmonary Defense Dysfunction.

Inhalants are volatile household chemicals that can directly affect the respiratory and nervous systems. Due to their legal and economic accessibility, they have emerged as a major social factor impacting the health of children and teenagers seeking pleasure. However, the detailed toxic mechanisms remain unclear. In the current study, we sprayed a single dose and repeated doses (weekly, totaling 1 to 5 times) of liquefied petroleum gas (LPG) to mice (12 male mice/group) and observed both local and systemic toxic effects. During exposure, we noted reduced eye blinking and noticeable tremors. The membrane of pulmonary alveolar macrophages was quickly damaged after inhalation, and pulmonary inflammatory mediator levels were significantly reduced in all groups inhaling LPG compared to the control. More importantly, serum concentrations of dopamine and corticosterone increased, peaking on Day 7 after the second exposure (6.1-fold) and the fourth exposure (3.7-fold), respectively. Next-generation sequencing analysis using total RNA extracted from the hippocampus of mice revealed that the expression of dopaminergic receptor D2 mRNA was downregulated in all groups exposed to LPG (-39.6 ± 0.0-fold at 30 min after the first exposure), and this decrease was confirmed by qRT-PCR analysis. Therefore, we suggest that inhalation of LPG may impair pulmonary defense functions by damaging the membranes of alveolar macrophages and could lead to addiction by downregulating the dopamine D2 receptor expression in the hippocampus. We propose that stringent control of volatile household chemical products is necessary worldwide to prevent diseases caused by misuse or abuse, particularly among young people.