Self-Administration of Toluene Vapor in Rats

Abstract

Inhalants, including volatile organic solvents such as toluene, continue to be one of the most prevalent, and often first substances abused by adolescents. Like other drugs of abuse, toluene affects the function of neurons within key brain reward circuits including the prefrontal cortex, ventral tegmental area, and nucleus accumbens. However, preclinical models used to study these toluene-induced adaptations generally employ passive exposure paradigms that do not mirror voluntary patterns of solvent exposure observed in humans. To address this shortcoming, we developed an inhalation chamber containing active and inactive nose pokes, cue lights, flow-through vaporizers, and software-controlled valves to test the hypothesis that rats will voluntarily selfadminister toluene vapor. Following habituation and self-administration (SA) training rats achieve vapor concentrations associated with rewarding effects of toluene, and maintain responding for toluene vapor, but not for air. During extinction trials, rats showed an initial burst of drug-seeking behavior similar to that of other addictive drugs and then reduced responding to Air SA levels. Responding on the active nose poke recovered during cueinduced reinstatement but not following a single passive exposure to toluene vapor. The results from these studies establish a viable toluene SA protocol that will be useful in assessing toluene-induced changes in addiction neurocircuitry.

A brief exposure to toluene vapor alters the intrinsic excitability of D2 medium spiny neurons in the rat ventral striatum

“…For example, a brief exposure of adolescent rats to toluene vapor induced an increase in the AMPA/NMDA ratio of dopamine neurons in the ventral tegmental area (VTA) that project to the nucleus accumbens (NAc) but no change in those projecting to the medial prefrontal cortex (mPFC) similar to that reported for other abused drugs ( Lammel et al, 2011 ; Beckley et al, 2013 ). Repeated exposures to toluene vapor induces a conditioned place preference (CPP) in rodents ( Funada et al, 2002 ; Wayman and Woodward, 2018a ) while rats, mice and monkeys can learn to self-administer toluene vapor ( Wood et al, 1977 ; Blokhina et al, 2004 ; Braunscheidel et al, 2020 ). In the CPP study from our laboratory, toluene exposure produced selective effects on the excitability of mPFC neurons projecting to different areas of the NAc and the expression of conditioned place preference was blocked by chemogenetic excitation of mPFC neurons that project to the NAc shell ( Wayman and Woodward, 2018a ).…”