Toluene-induced locomotor activity is blocked by 6-hydroxydopamine lesions of the nucleus accumbens and the mGluR2/3 agonist LY379268

A. C. Riegel, S. F. Ali, Edward D French

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1440-1447
Number of pages8
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume28
Issue number8
DOIs
StatePublished - Aug 2003

Fingerprint

LY 379268
Oxidopamine
Nucleus Accumbens
Toluene
Locomotion
Street Drugs
Synaptic Transmission
Dopamine
Inhalant Abuse
Primates
Substance-Related Disorders
Rodentia
metabotropic glutamate receptor 2
Brain

Keywords

  • 6-hydroxydopamine
  • Dopamine
  • Inhalant abuse
  • Metabotropic glutamate receptors
  • Nucleus accumbens
  • Toluene

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Toluene-induced locomotor activity is blocked by 6-hydroxydopamine lesions of the nucleus accumbens and the mGluR2/3 agonist LY379268",
abstract = "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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