Effects of volatile solvents on recombinant <i>N</i>‐methyl‐<scp>D</scp>‐aspartate receptors expressed in <i>Xenopus</i> oocytes

Cruz, Silvia L.; Balster, Robert L.; Woodward, John J.

doi:10.1038/sj.bjp.0703666

Cited by 109 publications

(95 citation statements)

References 27 publications

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“…For example, Cruz et al [13] showed that toluene nearly eliminated NMDA-stimulated but not kainate-induced currents in Xenopus laevis oocytes with low millimolar potency suggesting that NMDA inhibition may be a common mechanism of action for abused inhalants. Toluene also produced dose-dependent and reversible increases in GABA A and glycine receptor functioning in both Xenopus oocytes and rat hippocampal slices [7].…”

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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“…Typically inactive, mGluRs function as autoreceptors during elevated neuronal activity to attenuate DA, GABA, glutamate, and acetylcholine release (Cartmell and Schoepp, 2000). Given the widespread influence of mGluRs and the list of ion channel and G-protein coupled receptors affected by toluene, further research is necessary to clarify the cellular sequence of events underlying any toluene-induced behavior (Bale et al, 2002;Cruz et al, 1988;Beckstead et al, 2000;Tsuga et al, 1999Tsuga et al, , 2002. Nevertheless, the above observations at the systems level are consistent with the fact that LY379268 similarly reduces the DA-dependent behavioral effects of PCP and to a lesser extent those of amphetamine (Moghaddam and Adams, 1998;Cartmell et al, 1999Cartmell et al, , 2000aClark et al, 2002).…”

Section: Ly379268 Studies and Toluenementioning

confidence: 99%

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

Riegel

Ali

French

2003

Neuropsychopharmacol

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The abuse of volatile inhalants remains a prominent, yet poorly understood, form of substance abuse among youth. Nevertheless, the identification of a mechanism underlying the reinforcing properties of inhalants has been hampered by the lack of a clearly identifiable neural substrate upon which these chemicals act. One ingredient that is common to many abused inhalants is toluene, an organic solvent that is self-administered by nonhuman primates and rodents. Most drugs of abuse have been found to elicit forward locomotion in rats, an effect owing to the activation of mesoaccumbal dopamine (DA) pathways. Thus, the present study was undertaken using two different approaches to determine whether toluene-induced locomotor hyperactivity is also ultimately dependent upon DA neurotransmission in the mesolimbic nucleus accumbens (NAC). Here we report on the effects of 6-hydroxydopamine (6-OHDA) lesions of the NAC or pretreatment with the metabotropic mGlu2/3 receptor agonist LY379268 on toluene-induced locomotor activity. Both procedures, which are known to alter neurotransmission within the NAC, significantly attenuated toluene's locomotor stimulatory effects. These results provide strong support for a central mechanism of action of inhalants, which in the past has been more typically attributed to general nonspecific mechanisms throughout the brain. Moreover, as with other drugs of abuse, the NAC may be the final common pathway subserving toluene's abuse liability.

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“…In addition overall membrane integrity was maintained even though these receptors are sensitive to ethanol (27). These findings also suggest that toluene does not act as a competitive inhibitor of glutamate and the inhibitory effects are not due to it being a direct channel blocker (27). The authors suggest that toluene may affect the transmembrane domain of the receptor thus influencing channel state.…”

Section: Ionotropic Receptor Expressionmentioning

confidence: 59%

“…However toluene had little effect on currents induced in other ionotropic glutamate receptors including 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) GluA1 or GluA1/2 subunits or kainate GluK2 (old nomenclature GluR6 presented in paper) subunits. In addition overall membrane integrity was maintained even though these receptors are sensitive to ethanol (27). These findings also suggest that toluene does not act as a competitive inhibitor of glutamate and the inhibitory effects are not due to it being a direct channel blocker (27).…”

Section: Ionotropic Receptor Expressionmentioning

confidence: 80%

“…Using transfected Xenopus oocytes initial studies by Cruz et al, 1998, which were subsequently replicated by Beckley and Woodward in 2011 using whole-cell patch clamping of rodent medial prefrontal cortex neurons, found that exposure to toluene dose-dependently affects ligandgated ion channels that regulate neuronal excitation, inhibiting NMDA-mediated currents in a rapid and reversible manner (27,28). This effect was subunit dependent with combinations of GluN1/2B being more sensitive than GluN1/2A or GluN1/2C.…”

Section: Ionotropic Receptor Expressionmentioning

confidence: 99%

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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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Effects of volatile solvents on recombinant N‐methyl‐D‐aspartate receptors expressed in Xenopus oocytes

Cited by 109 publications

References 27 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

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

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

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