Chronic intermittent toluene inhalation in adolescent rats results in metabolic dysfunction with altered glucose homeostasis.
OBJECTIVE
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.


METHODS
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.


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.


CONCLUSIONS
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.
Division of Behavioural Neuroscience, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
A L W
AL
Dick
Division of Behavioural Neuroscience, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia.
A
A
Simpson
Division of Behavioural Neuroscience, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia.
A
A
Qama
Department of Physiology, Monash University, Clayton, Vic., Australia.
Z
Z
Andrews
Division of Behavioural Neuroscience, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia.
A J
AJ
Lawrence
Division of Behavioural Neuroscience, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia.|Department Anatomy and Neuroscience, University of Melbourne, Melbourne, Vic., Australia.
J R
JR
Duncan
D000280:Administration, Inhalation; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D014050:Toluene / Q000008:administration & dosage / Q000633:toxicity*
D014050:Toluene; D005947:Glucose