The Abused Inhalant Toluene Increases Dopamine Release in the Nucleus Accumbens by Directly Stimulating Ventral Tegmental Area Neurons

Riegel, Arthur C.; Zapata, Agustín; Shippenberg, Toni S.; French, Edward D.

doi:10.1038/sj.npp.1301273

Cited by 90 publications

(66 citation statements)

References 89 publications

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“…In line with this idea, it has been demonstrated that toluene exposure increases dopamine release and dopaminergic neuron activity in the mesolimbic system [24,45]. The sensitization theory of addiction [46,47] suggests that an increase in locomotor activity can predict reinforcing drug effects and addiction liability.…”

Section: Locomotor Effectsmentioning

confidence: 89%

Long-Term Behavioral Consequences of Prenatal Binge Toluene Exposure in Adolescent Rats

López‐Rubalcava¹,

Chávez-Alvarez²,

Huerta-Rivas³

et al. 2014

Journal of Drug and Alcohol Research

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The continued abuse of inhaled organic solvents, especially among women of childbearing age, raises the risk of long-term behavioral effects of maternal toluene abuse. In this study, the effects of short-term exposures to high toluene concentrations (i.e., "binges") were tested in independent groups of adolescent rats with different toluene treatments: (a) acute: 30-day-old animals exposed for 30 min to air (A) or 6,000 ppm toluene (T); (b) prenatal and postnatal: rats exposed to T or A from gestation days 8-20 and re-exposed to T or A from postnatal day (PN) 22 to PN30 (A/A, T/A, A/T, and T/T, resp.). On PN30, animals were evaluated in different tests. Postnatal toluene exposure produced anxiolytic-like effects in the burying behavior test, and the T/T group received the highest number of electrical shocks. Antinociception was observed in the T, A/T, and T/T groups in the hotplate test. All toluene treatments impaired short-term memory in the object recognition test, but only postnatal exposure impaired long-term memory in the passive avoidance test. Sensitization occurred in the T/T group in locomotor activity. These results indicate that prenatal exposure to a concentration of toluene that does not produce evident malformations can modify behavioral toluene's effects in adolescent rats.

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Section: Locomotor Effectsmentioning

confidence: 89%

Long-Term Behavioral Consequences of Prenatal Binge Toluene Exposure in Adolescent Rats

López‐Rubalcava¹,

Chávez-Alvarez²,

Huerta-Rivas³

et al. 2014

Journal of Drug and Alcohol Research

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Section: Neuropharmacological Bases Of Toluene Abusementioning

confidence: 99%

“…For example, brief (1-15 min) exposures to 11,500 ppm toluene produce a transient increase in neuronal firing in the ventral tegmental area (VTA) [Riegel and French 1999a;1999b;Riegel et al 2007]. Like cocaine, toluene increases extracellular dopamine levels in the prefrontal neocortex [Gerasimov et al 2002b] and nucleus accumbens [Riegel et al 2007]. Another study found that toluene alone did not increase dopamine levels in the nucleus accumbens, but did greatly exacerbate the increase caused by cocaine [Beyer et al 2001;Gerasimov et al 2002a;Riegel et al 2003].…”

Section: Neuropharmacological Bases Of Toluene Abusementioning

confidence: 99%

Reproductive Toxicology and Teratology of Abused Toluene

Hannigan

Bowen

2010

Systems Biology in Reproductive Medicine

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Reproductive Toxicology and Teratology of Abused TolueneToluene is an organic solvent that is widely used by industry and is ubiquitous in our environment. As a result, exposure to solvents like toluene in workrelated settings (i.e., relatively constant, low-level exposures) or through inhalant abuse (i.e., relatively intermittent, high-level exposures) is increasing for many women of reproductive age. Evidence suggests that the risk for pregnancy problems, as well as developmental delays and neurobehavioral difficulties, is higher for the children of women who have been exposed to high concentrations of organic solvents during pregnancy than for those who have not. These risks appear to be higher in cases of abuse exposure to solvents such as toluene, particularly in comparison to the risk for teratogenic outcomes with occupational solvent exposure. Despite this, the reproductive toxicology and teratology following abuse of toluene and other inhalants remains under-investigated. This brief review describes the current state of our understanding of the reproductive and teratogenic risk of gestational toluene abuse. The data to date suggest that the high levels of toluene exposure typical with inhalant abuse are more detrimental to fetal development than typical occupational exposure, and preclinical paradigms can be beneficial for investigating the processes and risks of prenatal solvent exposure. While substantial research has been done on the reproductive effects of occupational exposures to organic solvents, more research is needed on the outcomes and mechanisms of exposures typical of inhalant abuse.

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“…Increased toluene-induced locomotor activity can be attenuated by pre-treatment with remoxipride, a dopamine D 2 receptor antagonist (19) suggesting that this hyperactivity is mediated via dopamine-dependent mechanisms. These observations have been refined illustrating that toluene's effects can be attributed to time dependent increases in the action potential drive of VTA neurons which enhances dopamine release at projection sites (20). Furthermore the magnitude of firing does not decline following prolonged exposure (20), leading to persistent dopaminergic dysfunction.…”

Section: The Effects Of Inhalants On the Dopaminergic Systemmentioning

confidence: 96%

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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The Abused Inhalant Toluene Increases Dopamine Release in the Nucleus Accumbens by Directly Stimulating Ventral Tegmental Area Neurons

Cited by 90 publications

References 89 publications

Long-Term Behavioral Consequences of Prenatal Binge Toluene Exposure in Adolescent Rats

Long-Term Behavioral Consequences of Prenatal Binge Toluene Exposure in Adolescent Rats

Reproductive Toxicology and Teratology of Abused Toluene

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

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