Abuse pattern of toluene exposure alters mouse behavior in a waiting-for-reward operant task

Abstract

Inhaling solvents for recreational purposes continues to be a world-wide public health concern. Toluene, a volatile solvent in many abused products, adversely affects the central nervous system. However, the long-term neurobehavioral effects of exposure to high-concentration, binge patterns typical of toluene abuse remain understudied. We studied the behavioral effects of repeated toluene exposure on cognitive function following binge toluene exposure on behavioral impulse control in Swiss Webster mice using a "wait-for-reward" operant task. Mice were trained on a fixed-ratio (FR) schedule using sweetened milk as a reward. Upon achieving FR15, a wait component was added which delivered free rewards in the absence of responses at increasing time intervals (2 sec, 4 sec, 6 sec, etc…). Mice continued to receive free rewards until they pressed a lever that reinstated the FR component (FR Reset). Once proficient in the FR-Wait task, mice were exposed to either 1,000 ppm, 3,600 ppm or 6,000 ppm toluene, or 0 ppm (air controls) for 30 min per day for 40 days. To avoid acute effects of toluene exposure, behavior was assessed 23 hours later. Repeated toluene exposure decreased response rates, the number of FR resets, and increased mean wait time, resulting in a higher response-to-reinforcer ratio than exhibited by controls. Mice receiving the higher exposure level (6,000 ppm) showed a dramatic decrease in the number of rewards received, which was reversed when toluene exposure ceased. Mice receiving the lower exposure level (1,000 ppm) showed little change in the number of rewards. These results indicate that repeated binge exposures to high concentrations of toluene can significantly interfere with performance as measured by a waiting-forreward task, suggesting a significant impact on cognitive and/or psychomotor function. IntroductionIntentionally inhaling chemical fumes to achieve euphoric effects continues to be a popular method of drug abuse throughout the world [34] in part because of the ready availability of many products to "huff" and the uncomplicated methods of administration. Paint thinners, gasoline, nail polish remover and many commonly used household cleaning products are potential sources of abused chemicals. Exposure levels during episodes of abuse are much higher than concentrations present during typical occupational or incidental exposures to these same chemicals. For example, in contrast to an 8-hr exposure to ~100 ppm of toluene in a workplace, abuse typically can involve >20 deep inhalations of very high solvent concentrations (likely more than 5,000 ppm) over a very short period of time (10-15 min) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be dis...

Developmental Exposure to Concentrated Ambient Particles and Preference for Immediate Reward in Mice

“…The increase in FR resets demonstrated with postnatal CAPS suggests a preference for shorter rather than long delays, even if it requires the added response cost of the completion of an additional FR of 25 responses. Similar alterations in waiting behavior were seen in lead-treated rats (Brockel and Cory-Slechta 1998, 1999) and toluene-treated mice (Bowen and McDonald 2009). …”

“…Given the epidemiological evidence suggesting that ambient air pollution is associated with cognitive dysfunctions and other behavioral impairments, as well as with adverse impacts in regions and neurotransmitters within the frontostriatal CNS circuitry, we sought to determine if CAPS exposure during early postnatal life in mice would alter responding to delayed reward assessed using a fixed-ratio waiting-for-reward (FR wait) paradigm previously shown to be sensitive to other toxicants (Bowen and McDonald 2009; Brockel and Cory-Slechta 1998, 1999). In addition, we examined whether any observed effects on the FR wait schedule might be enhanced by subsequent additional adult exposures or influenced by changes in activity levels.…”

Differential effects of inhaled toluene on locomotor activity in adolescent and adult rats

“…While the 16,000-ppm concentration of toluene is higher than what has been examined previously in rodents, these results are in general agreement with previous studies using adult rats (Himnan, 1984, Hinman, 1987, Yavick et al, 1994) and adult mice (Bowen and Balster, 1998a, Bushnell et al, 1985, Wood and Colotla, 1990) in which the acute locomotor effects of inhaled toluene were shown to be biphasic, with excitation at concentrations below 4,000 ppm and sedation with motor impairment at concentrations above 6,000 ppm. However, to our knowledge, this is the first study to study shorter 5-min repeated binge toluene exposures, perhaps more faithfully modeling some abuse patterns in teens (including “cuffing”), in comparison to the longer exposure patterns used in previous investigations (Balster et al, 1997, Bowen, 2009, Bowen and Balster, 1996, 1997, 1998a, b, Bowen and McDonald, 2009, Bowen et al, 1996a, Bowen et al, 1996b, Himnan, 1984, Hinman, 1987). …”

Comparison of toluene-induced locomotor activity in four mouse strains

“…(This “acute” or “Pre Chronic” exposure phase of the study was completed before the repeated, i.e., so-called “Post Chronic” exposure phase). The concentrations of toluene selected for acute administration were based on previous investigations of toluene in our laboratory (Bowen and Balster, 1998, Bowen and McDonald, 2009). …”