1. ¹ORYGEN Research Centre, Department of Psychiatry, The University of Melbourne, Melbourne, Australia
2. ²Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne, Melbourne, Victoria, Australia
3. ³Howard Florey Institute, Centre for Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia

Correspondence: Associate Professor DI Lubman, ORYGEN Research Centre, 35 Poplar Road (Locked Bag 10), Parkville, Victoria 3052, Australia. E-mail: dan.lubman@mh.org.au

Received 21 November 2007; Revised 31 January 2008; Accepted 12 February 2008; Published online 10 March 2008.

Abstract

Experimentation with volatile substances (inhalants) is common during early adolescence, yet limited work has been conducted examining the neurobiological impact of regular binge use during this key stage of development. Human studies consistently demonstrate that chronic use is associated with significant toxic effects, including neurological and neuropsychological impairment, as well as diffuse and subtle changes in white matter. However, most preclinical research has tended to focus on acute exposure, with limited work examining the neuropharmacological or toxicological mechanisms underpinning these changes or their potential reversibility with abstinence. Nevertheless, there is growing evidence that commonly abused inhalants share common cellular mechanisms, and have similar actions to other drugs of abuse. Indeed, the majority of acute behavioural effects appear to be underpinned by changes in receptor and/or ion channel activity (for example, GABA_A, glycine and 5HT₃ receptor activation, NMDA receptor inhibition), although nonspecific interactions can also arise at high concentrations. Recent studies examining the effects of toluene exposure during the early postnatal period are suggestive of long-term alterations in the function of NMDA and GABA_A receptors, although limited work has been conducted investigating exposure during adolescence. Given the critical role of neurotransmitter systems in cognitive, emotional and brain development, future studies will need to take account of the substantial neuromaturational changes that are known to occur in the brain during childhood and adolescence, and to specifically investigate the neuropharmacological and toxicological profile of inhalant exposure during this period of development.