Proton MR Spectroscopy in Solvent Abusers<sup>a</sup>

Noda, S.; Yamanouchi, Naoto; Okada, Shinichi; Kodama, Kazuhiro; Murakami, Atsuhiro; Sekine, Hiroshi; Sakamoto, Tadashi; Komatsu, Naoya; Sato, Toshio; Ikehira, Hiroo; Morita, Fuminori

doi:10.1111/j.1749-6632.1996.tb17466.x

Cited by 8 publications

(4 citation statements)

References 7 publications

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“…While the precise nature of toluene-induced neurotoxicity and its mechanism(s) of action remain to be elucidated, results from previous studies suggest that several systems in addition to the monoamines may be involved, including cholinergic, GABAergic and glutaminergictransmitters [3,4,5,15,33]. Dose-dependent effects of solvent abuse include cerebellar damage [16,17,31,34], white matter abnormalities, such as MRI hyperintensities in cerebrum, thalamus, basal ganglia and cerebellum, and neuronal atrophy of hippocampus, corpus callosum and cerebellar vermis [30,31,37,39,41,42,49,50]. MR imaging of chronic toluene abusers consistently reveals lesions including T-2 hypo-or hyper-intensities throughout brain, including atrophy and white matter changes [30,45,48,49].…”

Section: Discussionmentioning

confidence: 99%

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats

Bowen

Mohammadi

Batis

et al. 2007

Neurotoxicology and Teratology

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The abuse of volatile organic solvents (inhalants) continues to be a major health concern throughout the world. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. The neurobehavioral teratogenic sequelae of solvent abuse (i.e., repeated, brief inhalation exposures to very high concentrations of solvents) have not been examined thoroughly. In a preclinical model of inhalant abuse, timed-pregnant Sprague-Dawley rats were exposed to 0, 8,000, or 12,000 parts per million (ppm) for 15 min twice daily from gestation day 8 (GD8) through GD20. In the first experiment, separate groups of offspring were observed individually in an open-field on postnatal day 22 (PN22), PN42 or PN63. In the second experiment, other offspring given identical prenatal toluene exposures were observed in an "open-field" following an acute i.p. injection of amphetamine (0, 0.56, 1.78 mg/kg) on PN28. Automated measurements of distance traveled and ambulatory time were recorded. Prenatal toluene exposure resulted in small alterations in spontaneous activity compared to non-exposed rats. Prenatal exposure to 12,000 ppm toluene resulted in significant hyposensitivity to the locomotor stimulatory effects of the amphetamine challenge in male but not female rats on PN28. The results demonstrate that prenatal exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous and amphetamine-induced locomotor behavior in rats. The expression of these effects also appears to depend upon the postnatal age of testing. These results imply that abuse of organic solvents during pregnancy in humans may also produce long-lasting effects on biobehavioral development.

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Section: Discussionmentioning

confidence: 99%

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats

Bowen

Mohammadi

Batis

et al. 2007

Neurotoxicology and Teratology

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“…Dose-dependent effects of chronic solvent abuse include cerebellar damage [14,15,25,28], white matter abnormalities, (including MRI T2 hypo- or hyper-intensities in cerebrum, thalamus, basal ganglia and cerebellum) [22,44,48], and neuronal atrophy of hippocampus, corpus callosum and cerebellar vermis [11,35,36,40,48,49]. Long-term inhalation of solvents, particularly toluene, is also associated with a number of severe neurological signs in people, including cerebellar ataxia, peripheral neuropathy, convulsions, and encephalopathy [13,20,23,28].…”

Section: 0 Introductionmentioning

confidence: 99%

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

Bowen

McDonald

2009

Neurotoxicology and Teratology

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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...

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“…The majority of absorbed toluene is metabolized by cytochrome P-450 (CYP) enzymes in the liver, primarily to benzyl alcohol and is eventually eliminated in the urine as hippuric acid [44]. In humans, exposure to high concentrations of toluene can have numerous deleterious effects including cerebellar damage [18,19,41,42], wide-ranging neuronal atrophy, and white matter abnormalities [35,41,46,48,51,63] as well as neurological syndromes such as ataxia, myopathy, peripheral neuropathy, convulsions, and encephalopathy [17,19,29,36,42]. Children who have been exposed to toluene in utero may also suffer from deficits in later development [7,32].…”

Section: Introductionmentioning

confidence: 99%

Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure☆

Bowen¹,

Hannigan²,

Irtenkauf³

2007

Reproductive Toxicology

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Inhalation of organic solvents is a persistent form of drug abuse with particular concern being the abuse of inhalants by women of child-bearing age. While studies have begun assessing postnatal outcomes of offspring exposed prenatally to inhalants, relatively little is known about the distribution of toluene in blood and body tissues of pregnant, inhalant-abusing women, or in the fetuses. The present study assessed the tissue toluene levels attained following brief toluene exposures using a pre-clinical rat model of maternal inhalant abuse. Timed-pregnant Sprague-Dawley rats were exposed to toluene at 8,000 or 12,000 parts per million (ppm) for 15, 30 or 45 min/exposure. Exposures occurred twice each day from gestational day 8 (GD8) through GD20. Immediately following the second exposure on GD8, GD14 and GD20 blood was taken from the saphenous vein of the dams. Following saphenous vein blood collection on GD20, dams were sacrificed and trunk blood was collected along with maternal tissue specimens from cerebellum, heart, lung, kidney and liver. The placenta, amniotic fluid and fetal brain were also collected. Results demonstrated that maternal saphenous blood toluene levels increased as the inhaled concentration of toluene and duration of exposure increased. The maternal cerebellum, heart, kidney and liver appeared to be saturated after 30 min on GD20 such that toluene levels in those organs were equivalent across all ambient concentrations of inhaled toluene. Toluene levels also increased in fetal brain as the inhaled concentration of toluene increased and in placenta and amniotic fluid as the duration of exposure increased. Toluene levels in all tissues at GD20, except maternal lung and amniotic fluid, were higher than in maternal saphenous blood suggesting that toluene concentrated in those organs. Measurement of toluene levels in blood and other tissues following repeated toluene exposure demonstrated that toluene readily reaches a variety of potential sites of action throughout the maternal-placental-fetal unit.

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Proton MR Spectroscopy in Solvent Abusers^a

Cited by 8 publications

References 7 publications

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats

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

Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure☆

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Proton MR Spectroscopy in Solvent Abusersa

Cited by 8 publications

References 7 publications

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats

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

Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure☆

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About

Proton MR Spectroscopy in Solvent Abusers^a