Alterations in glutamatergic and gabaergic ion channel activity in hippocampal neurons following exposure to the abused inhalant toluene

Bale, Ambuja S.; Tu, Y.; Carpenter-Hyland, Ezekiel P.; Chandler, L. Judson; Woodward, John J.

doi:10.1016/j.neuroscience.2004.08.040

Cited by 106 publications

(63 citation statements)

References 33 publications

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“…Mechanistic studies have suggested that these behavioral differences may co-occur with developmental changes in underlying neural systems [for review [55]], including alterations in GABA A receptor binding [33]. Similar to ethanol, toluene interacts with GABA A receptors [1,2], suggesting that this mechanism may also contribute to the age differences observed in the present study. In addition, younger animals have been shown to develop less locomotor sensitization than adult animals following repeated exposure to other drugs of abuse such as alcohol [12], [39], cocaine [14], [29], amphetamine [28], and methylphenidate [9,10].…”

Section: Discussionmentioning

confidence: 70%

Decreased sensitivity in adolescent vs. adult rats to the locomotor activating effects of toluene

Bowen¹,

Charlesworth²,

Tokarz³

et al. 2007

Neurotoxicology and Teratology

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Volatile organic solvent (inhalant) abuse continues to be a major health concern throughout the world. Of particular concern is the abuse of inhalants by adolescents because of its toxicity and link to illicit drug use. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. While studies have assessed outcomes of exposure to inhalants in adult male animals, there is little research on the neurobehavioral effects of inhalants in female or younger animals. In attempt to address these shortcomings, we exposed male and female Long-Evans rats to 20 min of 0, 2,000, 4,000, or 8,000 parts per million (ppm) inhaled toluene for 10 days in rats aged postnatal (PN) day 28-39 (adolescent), PN44-PN55, or >PN70 (adult). Animals were observed individually in 29-l transparent glass cylindrical jars equipped with standard photocells that were used to measure locomotor activity. Toluene significantly increased activity as compared to air exposure in all groups of male and female rats with the magnitude of locomotor stimulation produced by 4000 ppm toluene being significantly greater for female adults than during any age of adolescence. The results demonstrate that exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous locomotor behavior in rats and that the expression of these effects appears to depend upon the postnatal age of testing and sex of the animal.

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Section: Discussionmentioning

confidence: 70%

Decreased sensitivity in adolescent vs. adult rats to the locomotor activating effects of toluene

Bowen¹,

Charlesworth²,

Tokarz³

et al. 2007

Neurotoxicology and Teratology

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“…Interestingly, the amphetamine challenge at PN28 appears to reveal a small functional impact of toluene on maturation of monoaminergic systems supporting locomotor activity that is not evident in spontaneous behavior. 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].…”

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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“…Toluene-induced changes to NMDA-mediated currents were also associated with increased expression of GluN1 (at the cellular level), GluN2A and GluN2B (at the protein level) subunits (30); increased GluN1 and GluN2B levels in the prefrontal cortex being associated with increased AMPA GluA2/3 subunits (31). The authors suggest that toluene induces compensatory functional changes to ion channels regulating neuronal excitability and this may lead to glutamatergic driven hyperexcitability during withdrawal thus predisposing individuals to relapse vulnerability (30). In support of tolueneinduced changes to NMDA receptor sensitivity/function, our own studies have reported long-term effects on NMDA receptor mediated behaviours that were sustained into adulthood up to 20 days after the last exposure following chronic intermittent toluene inhalation experienced during adolescence in rats (32).…”

Section: Ionotropic Receptor Expressionmentioning

confidence: 80%

“…Specific effects of toluene on NMDA receptors have been further highlighted using rat hippocampal primary cultures, where toluene can dose-dependently and reversibly inhibit NMDA-mediated currents with no effects on currents mediated by the non-NMDA glutamate receptor agonist AMPA and only at high doses were effects on kainateinduced currents observed (30). However, in neurons that had been chronically treated with toluene (1 mM for 4 days) there were enhanced NMDA-mediated responses.…”

Section: Ionotropic Receptor Expressionmentioning

confidence: 99%

“…While toluene exposure has region-and subunitdependent effects on ionotropic glutamate receptors (primarily NMDA receptors) (27,28,30,31), to date only one paper has reported altered gene expression for metabotropic glutamate receptors (mGluRs) (namely, mGlu 1 and mGlu 7 ) following a single acute toluene exposure (33). There are data, however, to support that investigation into the role of mGluRs in mediating behaviors perpetuating inhalant abuse warrant further investigation as these receptors are believed to play a key role addiction (see ref.…”

Section: Metabotropic Receptor Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Conventional Concepts and New Perspectives for Understanding the Addictive Properties of Inhalants

Duncan

Lawrence

2013

J Pharmacol Sci

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Abstract. The abuse of inhaled chemical vapors is a growing problem especially among adolescent populations. This is partly driven by the fact that inhaled products are cheap, accessible, and provide a rapid 'high'. In the brain inhalants have multiple effects. They are neurotoxic, targeting primarily white matter pathways, which is believed to underlie the long-term neurological consequences associated with repeated use. Inhalants are also addictive, resulting in adaptive responses in pathways mediating reward and reinforcement. This includes an ability to alter dopaminergic cell firing and result in long-term mesocorticolimbic dopaminergic dysfunction. However, growing evidence suggests that the reinforcing properties of inhalants may also be driven by their ability to affect neurotransmitter systems other than the dopaminergic system. Both glutamatergic and g-aminobutyric acid (GABA)ergic systems are emerging as key targets of inhalants with differential responses observed following either acute or chronic exposures. These responses appear particularly important in circuits which appear vulnerable to inhalants and which can also modulate dopaminergic function such as the corticostriatal pathway. Thus in combination with the effects of inhalants on dopaminergic systems, our increased understanding of the role(s) of glutamatergic and GABAergic systems provide new and exciting targets to consider for intervention strategies to limit inhalant use.

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Alterations in glutamatergic and gabaergic ion channel activity in hippocampal neurons following exposure to the abused inhalant toluene

Cited by 106 publications

References 33 publications

Decreased sensitivity in adolescent vs. adult rats to the locomotor activating effects of toluene

Decreased sensitivity in adolescent vs. adult rats to the locomotor activating effects of toluene

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

Conventional Concepts and New Perspectives for Understanding the Addictive Properties of Inhalants

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