Distribution of c-Fos immunoreactivity in the rat brain following abuse-like toluene vapor inhalation

Perit, Kristina E.; Gmaz, Jimmie M.; Browne, James Donald Caleb; Matthews, Brittany A.; Dunn, M.B.; Yang, Linda; Raaphorst, Tanya; Mallet, Paul E.; McKay, Bruce E.

doi:10.1016/j.ntt.2011.10.007

Cited by 15 publications

(23 citation statements)

References 54 publications

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“…Together, this suggests that several neurotransmitter systems influence behaviours mediating rearing activity, many if not all of which are affected by toluene [68], [69]. However, due to the diversity of toluene's effects upon the brain [70], direct interpretation of the changes in rearing activity following CIT exposure is difficult.…”

Section: Discussionmentioning

confidence: 99%

Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

et al. 2012

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Inhalant misuse is common during adolescence, with ongoing chronic misuse associated with neurobiological and cognitive abnormalities. While human imaging studies consistently report white matter abnormalities among long-term inhalant users, longitudinal studies have been lacking with limited data available regarding the progressive nature of such abnormalities, including the potential for recovery following periods of sustained abstinence. We exposed adolescent male Wistar rats (postnatal day 27) to chronic intermittent inhaled toluene (3,000 ppm) for 1 hour/day, 3 times/week for 8 weeks to model abuse patterns observed in adolescent and young adult human users. This dosing regimen resulted in a significant retardation in weight gain during the exposure period (p<0.05). In parallel, we performed longitudinal magnetic resonance imaging (T2-weighted) and diffusion tensor imaging prior to exposure, and after 4 and 8 weeks, to examine the integrity of white matter tracts, including the anterior commissure and corpus callosum. We also conducted imaging after 8 weeks of abstinence to assess for potential recovery. Chronic intermittent toluene exposure during adolescence and early adulthood resulted in white matter abnormalities, including a decrease in axial (p<0.05) and radial (p<0.05) diffusivity. These abnormalities appeared region-specific, occurring in the anterior commissure but not the corpus callosum and were not present until after at least 4 weeks of exposure. Toluene-induced effects on both body weight and white matter parameters recovered following abstinence. Behaviourally, we observed a progressive decrease in rearing activity following toluene exposure but no difference in motor function, suggesting cognitive function may be more sensitive to the effects of toluene. Furthermore, deficits in rearing were present by 4 weeks suggesting that toluene may affect behaviour prior to detectable white matter abnormalities. Consequently, exposure to inhalants that contain toluene during adolescence and early adulthood appear to differentially affect white matter maturation and behavioural outcomes, although recovery can occur following abstinence.

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Section: Discussionmentioning

confidence: 99%

Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

et al. 2012

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“…Mimicking the route a drug is abused in humans has traditionally been thought to be of limited importance in preclinical studies, therefore the most convenient injection route is typically utilized. However, c-Fos expression in rats showed administration route-dependent differences in neuronal activation produced by toluene (Perit et al 2012). Among the important neuronal systems differentially affected by route were areas associated with reward and motor control, with inhaled toluene producing significant increases in c-Fos expression in the nucleus-accumbens core and caudate-putamen relative to the findings of a previous study using injected toluene (Lo and Chen 2005).…”

Section: Introductionmentioning

confidence: 99%

Assessment of reinforcement enhancing effects of toluene vapor and nitrous oxide in intracranial self-stimulation

2013

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Rationale Despite widespread abuse there are few validated methods to study the rewarding effects of inhalants. One model that that may have utility for this purpose is intracranial self-stimulation (ICSS). Objectives We wished to compare and contrast the ICSS reward-facilitating effects of abused inhalants to other classes of abused drugs. Compounds were examined using two different ICSS procedures in mice to determine the generality of each drug's effects on ICSS and the sensitivity of the procedures. Methods Male C57BL/6J mice with electrodes implanted in the medial forebrain bundle were trained under a three component rate-frequency as well as a progressive ratio (PR) ICSS procedure. The effects of nitrous oxide, toluene vapor, cocaine and diazepam on ICSS were then examined. Results Concentrations of 1360-2900 ppm inhaled toluene vapor significantly facilitated ICSS in the rate frequency procedure and 1360 ppm increased PR breakpoint. A concentration of 40% nitrous oxide facilitated ICSS in the rate-frequency procedure but reduced PR breakpoint. Doses of 3-18 mg/kg cocaine facilitated ICSS in the rate frequency procedure and 10 and 18 mg/kg increased PR breakpoint. Doses of 1 and 3 mg/kg diazepam facilitated ICSS in the rate frequency procedure and 3 mg/kg increased PR breakpoint. Conclusions The reinforcement facilitating effect of toluene in ICSS is at least as great as diazepam. In contrast, nitrous oxide weakly enhances ICSS in only the rate frequency procedure. The data suggest that the rate frequency procedure may be more sensitive than the PR schedule to the reward facilitating effects of abused inhalants.

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“…Experiments were completed with 5,000 ppm toluene vapor because this concentration is produced by spontaneously vaporizing toluene at room temperature, which therefore parallels the concentration of toluene vapors that can be inhaled by humans in acute abuse-like binge inhalation situations (5,000-15,000 ppm) (Cavender, 1994;Wilkins-Haug, 1997). Our own research has shown that 30 min of exposure to $5,000 ppm toluene vapor results in robust changes in the activity of numerous brain regions Perit et al, 2012). Duration of binge inhalation in human users is highly variable, and duration of exposure to abuse-like concentrations of toluene in animal studies is also highly variable, in both cases ranging from a few minutes to several hours, with toluene vapor exposure occurring either continuously or in an intermittent fashion.…”

Section: Introductionmentioning

confidence: 90%

“…Vapor exposure occurred in identical custom-constructed chambers as previously described in detail (Perit et al, 2012). Briefly, each chamber contained two fluid-filled reservoirs.…”

Section: Toluene Vapor Exposurementioning

confidence: 99%

“…In this study rats were exposed to 0, 8,000, or 16,000 ppm toluene over 12 days; rats received either two 15-min exposures separated by 105 min, two 15-min exposures separated by 15 min, or six 5-min exposures each separated by 25 min (Batis et al, 2010). Importantly, differences between these studies, in particular with respect to the different routes of administration used, different environmental concentrations of toluene, and different patterns of toluene exposure, may have produced dissimilar patterns of neural activation and/or resulting brain concentrations of toluene due to the markedly different "doses" received by the rats in different studies (Bushnell, Oshiro, Samsam, & Klinger, 2007;Kenyon et al, 2008;Lo & Chen, 2005;Perit et al, 2012). These authors found that male adolescent rats were less sensitive to the initial effects of toluene early in the 10 days of the exposure paradigm compared to the young adult rats.…”

Section: Open Field and Neurological Assessmentmentioning

confidence: 99%

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Age‐dependent time courses of recovery for motor functions following acute toluene intoxication in rats

Samuel-Herter

Slaght

McKay

2013

Developmental Psychobiology

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Toluene is a psychoactive chemical found in many household products including adhesives and thinners. Inhalation of these vapors can cause euphoria and impairments in motor control and neurological functioning. Misuse and abuse of toluene is most common in children, which may in part be due to an age-dependent neurobehavioral sensitivity to toluene. Here we assessed the effects of acute binge-like toluene inhalations (15 or 30 min; ∼5,000 ppm) on tasks that examine locomotion, exploration, balance, gait, and neurological functioning for adolescent (1 month), young adult (2-3 months), adult (5-6 months), and older adult (10-12 months) rats. Both motor and neurological functions were impaired following acute toluene inhalation at all ages. However, only the duration to recover from deficits in motor functions differed among age groups, with adolescent and young adult rats requiring notably longer recovery times than older rats. Our results are suggestive of an age-dependent vulnerability to the intoxicating effects of toluene.

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Distribution of c-Fos immunoreactivity in the rat brain following abuse-like toluene vapor inhalation

Cited by 15 publications

References 54 publications

Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

Assessment of reinforcement enhancing effects of toluene vapor and nitrous oxide in intracranial self-stimulation

Age‐dependent time courses of recovery for motor functions following acute toluene intoxication in rats

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