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Toluene inhalation in adolescent rats reduces flexible behaviour in adulthood and alters glutamatergic and GABAergic signalling
Author(s) -
Furlong Teri M.,
Duncan Jhodie R.,
Corbit Laura H.,
Rae Caroline D.,
Rowlands Benjamin D.,
Maher Anthony D.,
Nasrallah Fatima A.,
Milligan Carol J.,
Petrou Steven,
Lawrence Andrew J.,
Balleine Bernard W.
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13858
Subject(s) - glutamatergic , gabaergic , nmda receptor , prefrontal cortex , neuroscience , prepulse inhibition , glutamate receptor , hippocampus , psychology , medicine , receptor , endocrinology , biology , inhibitory postsynaptic potential , psychiatry , cognition , schizophrenia (object oriented programming)
Toluene is a commonly abused inhalant that is easily accessible to adolescents. Despite the increasing incidence of use, our understanding of its long‐term impact remains limited. Here, we used a range of techniques to examine the acute and chronic effects of toluene exposure on glutameteric and GABA ergic function, and on indices of psychological function in adult rats after adolescent exposure. Metabolomics conducted on cortical tissue established that acute exposure to toluene produces alterations in cellular metabolism indicative of a glutamatergic and GABA ergic profile. Similarly, in vitro electrophysiology in Xenopus oocytes found that acute toluene exposure reduced NMDA receptor signalling. Finally, in an adolescent rodent model of chronic intermittent exposure to toluene (10 000 ppm), we found that, while toluene exposure did not affect initial learning, it induced a deficit in updating that learning when response‐outcome relationships were reversed or degraded in an instrumental conditioning paradigm. There were also group differences when more effort was required to obtain the reward; toluene‐exposed animals were less sensitive to progressive ratio schedules and to delayed discounting. These behavioural deficits were accompanied by changes in subunit expression of both NMDA and GABA receptors in adulthood, up to 10 weeks after the final exposure to toluene in the hippocampus, prefrontal cortex and ventromedial striatum; regions with recognized roles in behavioural flexibility and decision‐making. Collectively, our data suggest that exposure to toluene is sufficient to induce adaptive changes in glutamatergic and GABA ergic systems and in adaptive behaviour that may underlie the deficits observed following adolescent inhalant abuse, including susceptibility to further drug‐use.