Effect of toluene on memory: A focus on humans, experimental models and treatment approaches

Abstract

Inhalants remain an understudied class of drugs, despite their extensive usage in industrial settings and ease of access for misuse, particularly among children and adolescents. Toluene is a primary component of many volatile solvents. Memory impairment is frequently observed in individuals exposed to toluene in occupational settings and as recreational drug. Experimental data shows that toluene produces abnormalities in the key neurotransmitters and receptors in the hippocampus, cortex, striatum, brain regions related to memory. Acute exposure to toluene stimulates the release of glutamate, dopamine, and serotonin while inhibiting the release of acetylcholine. Toluene inhibits NMDA-type glutamate and nicotinic cholinergic receptors, while upregulating GABA-A receptors. During chronic exposure, increased expression of NR2B subunits of the NMDA receptor is a consistent finding. Toluene has been observed to decrease neurogenesis in developing and adult brains and is also involved in oxidative damage and apoptosis, both interrelated phenomena, thus contributing to alterations in memory. To reverse the cognitive impairments caused by toluene, novel non-pharmacological procedures, such as environmental enrichment, have shown potential in both humans and experimental animals. Pharmacological treatments have also been experimentally evaluated, mainly through the glycine co-agonist site, of the NMDA receptor. The study of the mechanisms by which toluene causes neurotoxicity is important for developing strategies for reverting damage to executive functions in occupationally exposed workers, as well as in individuals with substance abuse.