Toluene exposure during the brain growth spurt reduces behavioral responses to noncompetitive N-methyl-d-aspartate receptor antagonists in adult rats

Chien, Te-Hsiung; Chan, Ming‐Huan; Tang, Yu-Chi; Chen, Hwei-Hsien

doi:10.1007/s00213-005-0137-x

Cited by 13 publications

(7 citation statements)

References 30 publications

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“…during the early postnatal period (postnatal day 4 (PN4) to PN9). These studies reported altered responses related to the glutamatergic system, with reduced hyperlocomotion induced by NMDA agonists ( Chien et al ., 2005 ), an increase in NR2A subunits in the hippocampus and cerebellum ( Lee et al ., 2005 ) and a decrease in NR2B levels (200–100 mg kg −1 i.p. from PN4 to PN7; Chen et al ., 2004 ).…”

Section: Developmental Issuesmentioning

confidence: 99%

Inhalant abuse among adolescents: neurobiological considerations

Lubman

Yücel

Lawrence

2008

British J Pharmacology

144

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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 5HT 3 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.

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Section: Developmental Issuesmentioning

confidence: 99%

Inhalant abuse among adolescents: neurobiological considerations

Lubman

Yücel

Lawrence

2008

British J Pharmacology

144

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“…The oxidative stress hypothesis is supported by studies showing that the administration of antioxidants such as melatonin can counter the neurotoxic effects of toluene (Baydas et al, 2003; Pascual et al, 2010). In addition, because glutamatergic NMDA receptors play an important role in neural development and plasticity (Cull‐Candy et al, 2001) and because toluene administered during the preweaning period significantly altered NMDA receptor expression and function (Chen et al, 2005; Chien et al, 2005; Lee et al, 2005), it is possible that NMDA dysfunction may significantly contribute to the structural cell impairments observed in this and previous developmental studies. Moreover, considering that GABAergic transmission is significantly altered by the inhalation of volatile solvents such as toluene (MacIver, 2009), and that GABA plays an important role in neuronal development (Takesian et al, 2010), it is likely that this is an additional mechanism by which the abuse of inhalants can alter neuronal development and function.…”

Section: Methodsmentioning

confidence: 84%

“…The solvent‐induced reduction in brain weight and size is consistent with a previous study in which rat pups exposed to toluene between P4 and P10 displayed a dose‐dependent decrease in brain weight and astrocytic markers (Burry et al, 2003). Similarly, intraperitoneal toluene administration to rat pups at P4–P7 significantly reduced brain weight and caused glutamatergic dysfunction and neurobehavioral abnormalities (Chen et al, 2005; Chien et al, 2005). The data obtained in previous studies and in the present study are consistent with “fetal solvent syndrome”, which is found in human infants whose mothers were exposed to solvents during pregnancy.…”

Section: Methodsmentioning

confidence: 99%

“…For example, in animals exposed the toluene fumes between P21 and P31, the mean number of dendritic branches/neuron was reduced ∼30% (Pascual et al, 2010); in the present study, however, dendritic branching was reduced ∼50% relative to age‐matched control rats. Although the studies are not entirely comparable, the increased neurotoxic effect of solvent inhalation in weanling rats could be partially explained by the higher rate of dendritic outgrowth that occurs during this critical ontogenetic stage (Chien et al, 2005; Miller, 1981; Takashima et al, 1980). It is also possible that the solvents (75% toluene and 18% n ‐hexane) may interact synergistically to impair neuronal maturation.…”

Section: Methodsmentioning

confidence: 99%

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Solvent inhalation (toluene and n‐hexane) during the brain growth spurt impairs the maturation of frontal, parietal and occipital cerebrocortical neurons in rats

Pascual

Aedo

Meneses

et al. 2010

Intl J of Devlp Neuroscience

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Solvent abuse during pregnancy may cause "fetal solvent syndrome", which is characterized by mild brain atrophy and associated with behavioral, cognitive, and emotional abnormalities. The present study investigated whether solvent inhalation during the preweaning period (P2-P21) alters the morphological maturation of frontal, parietal, and occipital cortical neurons. Twelve hours after delivery (postnatal day 0, P0), litters were cross-fostered, culled to 8 pups/dam and housed together with a dam in standard laboratory cages. Litters were randomly assigned to the "air-only" group (n=64, 8 litters) and to the "solvent-sniffer" group (n=72, 9 litters). During P2-P21, each animal was exposed daily to either organic solvent vapors (75% toluene and 18% n-hexane, a solvent mixture commonly found in glues and adhesives) or clean air. To determine the impact of early solvent inhalation on cortical neuronal differentiation, brains were stained using the Golgi-Cox-Sholl procedure to quantitatively assess neocortical pyramidal cell dendrogenesis. Preweaning, solvent-exposed animals displayed dramatic impairments in dendritic growth as well as significant reductions in brain weight and size.

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“…Animal studies support the notion that toluene is damaging to the developing brain, with one study in rats demonstrating a permanent reduction in forebrain myelination after prenatal exposure to toluene (Gospe & Zhou, 1998), while another found behavioral abnormalities in rats exposed to 95 96 M. TAKAGI ET AL. toluene postnatally during periods of high synaptogenesis (Bowen, Batis, Paez-Martinez, & Cruz, 2006;Chien, Chan, Tang, & Chen, 2005;Lubman, Yücel, & Lawrence, 2008; also see Cruz, in this issue).…”

Section: Introductionmentioning

confidence: 90%

Solvent-Induced Leukoencephalopathy: A Disorder of Adolescence?

Takagi

Lubman

Yücel

2011

Substance Use & Misuse

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Volatile substance misuse is common during early adolescence; however, limited work has been conducted investigating the neurobiological effects of such use on the developing brain. While both animal and human studies report cognitive and neurobiological harm associated with volatile substance misuse during adolescence (particularly involving white matter structures), the complex psychosocial characteristics of volatile substance misusers confound the specificity of reported volatile substance-related pathology in human subjects. In addition, few studies have examined whether cognitive and neurobiological recovery occurs with abstinence, although there is some literature indicating that neurological and cognitive improvement is possible, but relates to the frequency and duration of previous use. Longitudinal studies utilizing well-matched control samples are required to fully delineate the short- and long-term impact of volatile substance misuse on adolescent brain development.

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Toluene exposure during the brain growth spurt reduces behavioral responses to noncompetitive N-methyl-d-aspartate receptor antagonists in adult rats

Cited by 13 publications

References 30 publications

Inhalant abuse among adolescents: neurobiological considerations

Inhalant abuse among adolescents: neurobiological considerations

Solvent inhalation (toluene and n‐hexane) during the brain growth spurt impairs the maturation of frontal, parietal and occipital cerebrocortical neurons in rats

Solvent-Induced Leukoencephalopathy: A Disorder of Adolescence?

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