Anatomy and Neuroscience - Research Publications
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ItemToluene inhalation in adolescent rats reduces flexible behaviour in adulthood and alters glutamatergic and GABAergic signalling(WILEY-BLACKWELL, 2016-12)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 GABAergic 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 GABAergic 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 GABAergic systems and in adaptive behaviour that may underlie the deficits observed following adolescent inhalant abuse, including susceptibility to further drug-use.
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ItemThe effect of adolescent inhalant abuse on energy balance and growth(JOHN WILEY & SONS LTD, 2019-08)The abuse of volatile solvents such as toluene is a significant public health concern, predominantly affecting adolescents. To date, inhalant abuse research has primarily focused on the central nervous system; however, inhalants also exert effects on other organ systems and processes, including metabolic function and energy balance. Adolescent inhalant abuse is characterized by a negative energy balance phenotype, with the peak period of abuse overlapping with the adolescent growth spurt. There are multiple components within the central and peripheral regulation of energy balance that may be affected by adolescent inhalant abuse, such as impaired metabolic signaling, decreased food intake, altered dietary preferences, disrupted glucose tolerance and insulin release, reduced adiposity and skeletal density, and adrenal hypertrophy. These effects may persist into abstinence and adulthood, and the long-term consequences of inhalant-induced metabolic dysfunction are currently unknown. The signs and symptoms resulting from chronic adolescent inhalant abuse may result in a propensity for the development of adult-onset metabolic disorders such as type 2 diabetes, however, further research investigating the long-term effects of inhalant abuse upon energy balance and metabolism are needed. This review addresses several aspects of the short- and long-term effects of inhalant abuse relating to energy and metabolic processes, including energy balance, intake and expenditure; dietary preferences and glycemic control; and the dysfunction of metabolic homeostasis through altered adipose tissue, bone, and hypothalamic-pituitary-adrenal axis function.
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ItemNo Preview AvailableAdolescent inhalant abuse leads to other drug use and impaired growth; implications for diagnosis(WILEY, 2017-02)OBJECTIVE: Abuse of inhalants containing the volatile solvent toluene is a significant public health issue, especially for adolescent and Indigenous communities. Adolescent inhalant abuse can lead to chronic health issues and may initiate a trajectory towards further drug use. Identification of at-risk individuals is difficult and diagnostic tools are limited primarily to measurement of serum toluene. Our objective was to identify the effects of adolescent inhalant abuse on subsequent drug use and growth parameters, and to test the predictive power of growth parameters as a diagnostic measure for inhalant abuse. METHODS: We retrospectively analysed drug use and growth data from 118 Indigenous males; 86 chronically sniffed petrol as adolescents. RESULTS: Petrol sniffing was the earliest drug used (mean 13 years) and increased the likelihood and earlier use of other drugs. Petrol sniffing significantly impaired height and weight and was associated with meeting 'failure to thrive' criteria; growth diagnostically out-performed serum toluene. CONCLUSIONS: Adolescent inhalant abuse increases the risk for subsequent and earlier drug use. It also impairs growth such that individuals meet 'failure to thrive' criteria, representing an improved diagnostic model for inhalant abuse. Implications for Public Health: Improved diagnosis of adolescent inhalant abuse may lead to earlier detection and enhanced health outcomes.
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ItemNo Preview AvailableChronic intermittent toluene inhalation in adolescent rats results in metabolic dysfunction with altered glucose homeostasis(WILEY, 2015-11)BACKGROUND AND PURPOSE: Abuse of toluene-containing inhalants is an increasing public health problem, especially among adolescents. Abuse during adolescence is associated with emaciation, while industrial exposure leads to altered glycaemic control suggesting metabolic instability. However, the relationship between adolescent inhalant abuse and metabolic dysfunction remains unknown. EXPERIMENTAL APPROACH: To model human abuse patterns, we exposed male adolescent Wistar rats [postnatal day (PND) 27] to chronic intermittent inhaled toluene (CIT, 10,000 ppm) or air (control) for 1 h·day(-1) , three times a week for 4 weeks. Feeding and body composition were monitored. After 4 weeks, circulating metabolic hormone concentrations and responses to a glucose tolerance test (GTT) were measured. Dietary preference was measured by giving animals access to either a 'western diet' plus standard chow (WC + SC) or standard chow alone during 4 weeks of abstinence. Metabolic hormones and GTT were subsequently measured. KEY RESULTS: Adolescent CIT exposure significantly retarded weight gain, altered body composition, circulating metabolic hormones and responses to a GTT. While reduced body weight persisted, responses to a GTT and circulating hormones appeared to normalize for animals on standard chow following abstinence. In CIT-exposed WC + SC rats, we observed impaired glucose tolerance associated with altered metabolic hormones. Analysis of hypothalamic genes revealed differential expression profiles in CIT-exposed rats following both the exposure period and abstinence, suggesting a central contribution to inhalant-induced metabolic dysfunction. CONCLUSION AND IMPLICATIONS: CIT exposure during adolescence has long-term effects on metabolic function, which may increase the risk of disorders related to energy balance and glycaemic control.