Abused inhalants and central reward pathways: Electrophysiological and behavioral studies in the rat

Arthur C. Riegel, Edward D French

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Inhalant abuse remains a significant health problem among the younger segment of society. In fact, the use of inhalants in this population trails only that of nicotine, alcohol, and marijuana. Toluene is a common ingredient in many of the substances sought out for inhalation abuse, apparently for its euphorigenic and hallucinogenic effects. Because drugs of abuse share the common property of altering the activity of mesolimbic dopamine neurons, it is reasonable to suspect that toluene-induced changes in this CNS pathway may underlie its abuse potential. Here we will provide in vivo and in vitro electrophysiological data and behavioral evidence linking toluene exposure in rats to activation of mesolimbic dopamine neurons. Exposure of rats to 11,000 ppm of inhaled toluene produced time-dependent activation of dopamine neurons within the midbrain ventral tegmental area (VTA). In the rat brain slice preparation, perfusion with toluene (23-822 μM) also evoked an increase in activity of both dopamine and nondopamine neurons within the VTA. These excitatory effects could not be found in adjacent non-VTA nuclei, nor were they sensitive to the glutamate antagonists CGS19755 or CNQX. In behavioral studies, systemic administration of toluene produced a dose-dependent locomotor hyperactivity that was attenuated by either pretreatment with the D2 dopamine receptor antagonist remoxipride or by 6-hydroxydopamine lesions of the nucleus accumbens. These findings show that toluene can activate dopamine neurons within the mesolimbic reward pathway, an effect that may underlie the abuse potential of inhaled substances containing toluene.

Original languageEnglish (US)
Pages (from-to)281-291
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume965
StatePublished - 2002

Fingerprint

Toluene
Reward
Rats
Dopaminergic Neurons
Neurons
Dopamine
Ventral Tegmental Area
Remoxipride
Inhalant Abuse
Chemical activation
6-Cyano-7-nitroquinoxaline-2,3-dione
Excitatory Amino Acid Antagonists
Rat
Pathway
Oxidopamine
Nucleus Accumbens
Street Drugs
Cannabis
Medical problems
Mesencephalon

Keywords

  • Dopamine
  • Inhalants
  • Reward
  • Toluene
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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abstract = "Inhalant abuse remains a significant health problem among the younger segment of society. In fact, the use of inhalants in this population trails only that of nicotine, alcohol, and marijuana. Toluene is a common ingredient in many of the substances sought out for inhalation abuse, apparently for its euphorigenic and hallucinogenic effects. Because drugs of abuse share the common property of altering the activity of mesolimbic dopamine neurons, it is reasonable to suspect that toluene-induced changes in this CNS pathway may underlie its abuse potential. Here we will provide in vivo and in vitro electrophysiological data and behavioral evidence linking toluene exposure in rats to activation of mesolimbic dopamine neurons. Exposure of rats to 11,000 ppm of inhaled toluene produced time-dependent activation of dopamine neurons within the midbrain ventral tegmental area (VTA). In the rat brain slice preparation, perfusion with toluene (23-822 μM) also evoked an increase in activity of both dopamine and nondopamine neurons within the VTA. These excitatory effects could not be found in adjacent non-VTA nuclei, nor were they sensitive to the glutamate antagonists CGS19755 or CNQX. In behavioral studies, systemic administration of toluene produced a dose-dependent locomotor hyperactivity that was attenuated by either pretreatment with the D2 dopamine receptor antagonist remoxipride or by 6-hydroxydopamine lesions of the nucleus accumbens. These findings show that toluene can activate dopamine neurons within the mesolimbic reward pathway, an effect that may underlie the abuse potential of inhaled substances containing toluene.",
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