Journal
DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES
Volume 1139, Issue -, Pages 390-401Publisher
WILEY-BLACKWELL
DOI: 10.1196/annals.1432.031
Keywords
Inhalants; abused solvents; benzodiazepines; NMDA; mu-opioid receptors; autoradiography; receptor binding; pain; analgesia; hot plate
Categories
Funding
- Conacyt [43604-M, 138625, 45943-M]
- Ministerio de Educacion y Ciencia [SAF2004_08148]
- Red de trastornos adictivos, Fondo de Investigaciones Sanitarias [603/05]
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In vitro and in vivo studies have shown that abused solvents affect different neurotransmitter systems, including the GABAergic, glutamatergic, and opioidergic. The first purpose of this study was to determine in mice whether an acute exposure to 4,000 ppm toluene or 12,000 ppm 1,1,1-trichloroethane (TCE) modifies receptor binding levels to: (a) DAMGO, a mu-opioid receptor selective agonist; (b) MK-801, a noncompetitive selective NMDA-receptor antagonist; and (c) flunitrazepam, a benzodiazepine binding site selective agonist. In addition, in separate groups of animals, nociceptive effects of toluene alone or co-administered with morphine were evaluated in the hot-plate test. Mice were exposed to toluene or TCE in static exposure chambers for 30 min, and their brains were removed 24 h later for autoradiography. Acute toluene inhalation produced a significant decrease in mu-opioid receptor binding levels in cingulate and piriform cortices, caudate putamen, thalamus, amygdala, and periaqueductal gray, whereas TCE significantly decreased mu-opioid receptor levels, but only in thalamus and periaqueductal gray. Both toluene and TCE decreased benzodiazepine receptor binding levels in discrete brain areas, but had no effect on NMDA receptor levels. In the hot-plate test, a single toluene exposure counteracted morphine antinociceptive response when the solvent exposure time was immediately followed by morphine treatment, but not when morphine was administered 24, 48, 72, and 96 h later. However, co-administration of morphine and toluene 24, 48, 72, and 96 h after the single solvent exposure resulted in morphine-induced analgesia blockade. Present results suggest that mu-opioid receptors are an important molecular target for organic solvents, and that the inhalation of these compounds may affect the analgesic properties of opioids.
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