要旨
The purposeful inhalation of volatile solvents, such as toluene, to
induce self-intoxication is prevalent, particularly within adolescent
populations. Chronic misuse results in cognitive and neurobiological
impairments, as well as an increased risk for addictive behaviours in
adulthood. Toluene-induced neuroadaptations within mesocorticolimbic
circuitry are thought, in part, to mediate some of the adverse outcomes
of toluene misuse, however our understanding of the neuroadaptive
processes remains equivocal. An understanding of these processes is
particularly important relative to exposure that occurs during
adolescence and at concentrations that reflect various patterns of use.
Therefore, we exposed male adolescent Wistar rats (postnatal day [PN]
27) to either air or low or high concentrations of inhaled toluene in a
chronic and intermittent fashion (CIT, 3,000 or 10,000 ppm) for 1 h/day,
3-5 times per week for 4 weeks to model different patterns of human
inhalant abuse. Brains were subsequently analysed using autoradiography,
qPCR and immunohistochemistry 3 days following the exposure period to
investigate toluene-induced neuroadaptations within mesocorticolimbic
circuitry. In CIT-exposed rats binding to N-methyl-D-aspartate (NMDA)
receptors containing the GluN2B subunit, as determined using
[H-3]-ifenprodil, was decreased in a concentration-related manner in the
caudal cingulate cortex, dorsal striatum and accumbens; however, this
was not associated with changes in GluN2B protein expression. There were
no differences in [H-3]-epibatidine binding to heteromeric neuronal
nicotinic acetylcholine (nACh) receptors. Relative expression of mRNA
transcripts encoding NMDA, nACh, gamma-aminobutyric acid type-A
(GABA(A)) and dopamine receptor subunits was unchanged in all regions
assessed following CIT. Our data suggest that adolescent CIT exposure
impacts NMDA receptors within regions of corticostriatal circuitry,
possibly via post-translational mechanisms. Dysfunctional glutamatergic
signalling within corticostriatal regions may contribute to the adverse
outcomes observed following adolescent toluene abuse. (C) 2015 Elsevier
B.V. All rights reserved.
