Addiction Research & Therapy

Nowadays, it is quite acknowledged that inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing signifi cant morbidity and mortality particularly in school-aged and older children. Solvent inhalants are not illegal, easily accessible and inexpensive; which makes young people at an increased risk for their abuse and consequences, including death. Several studies were undertaken to elucidate the possible mechanisms(s) of inhalant abuse and toxicity. Some studies revealed that deaths associated with their abuse were traumatic and capable of killing directly probably via cardiac mechanisms. Other studies showed that inhalants can lead to severe damage to bone marrow, liver, kidney, brain, and heart. Various reports ascribed the neurotoxicity of inhalants to their eff ects on brain neurotransmitters. Inhalants were found to increase GABAA, glycine and 5-HT3 receptor activation. Toluene, TCE, benzene and diethyl ether produce anxiolytic eff ects, suggesting that they act as positive modulators of GABAA receptors. Toluene acutely inhibit nicotinic ACh receptors; whereas acute toluene exposure was shown to regulate hippocampal muscarinic receptor binding and could disrupt the activity of numerous voltage-gated ion channels, calcium signaling, ATPases and G-proteins. other studies reported that toluene, benzene, , diethyl ether, TCE, and xylene may block the NMDA receptors resulting in

CNS depression . Prolonged exposure to toluene increased levels of brain NMDA receptors. Toluene was reported to inhibit two types of potassium channels in brain cells. Exposure to toluene increased dopamine levels in the rat prefrontal cortex and striatum and increased neuronal fi ring in the ventral tegmental area (VTA) in a manner similar to other drugs of abuse which

could be integral to the rewarding Toluene caused alterations in catecholamines synthesis and utilization in a number of studies. Th e neurobiological effects of toluene may be mediated by GABA and glutamate receptors.

In a recent study in our laboratory, single and daily repeated Toluene inhalation signifi cantly altered levels of brain neurotransmitters. Toluene increased levels of glutamate and decreased levels of GABA. Toluene single and repeated daily inhalation increased 5-HT and dopamine levels in rat’s brain.

In this presentation, a trial is undertaken to throw some light on the role of brain neurotransmitters in solvent inhalant abuse and neurotoxicity. Th is might help in fi nding more adequate methods to treat and overcome the deleterious hazards of abusing these toxic substances.