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ItemChronic intermittent toluene inhalation initiated during adolescence in rats does not alter voluntary consumption of ethanol in adulthoodDick, ALW ; Lawrence, AJ ; Duncan, JR (ELSEVIER SCIENCE INC, 2014-09-01)Voluntary inhalation of organic solvents, such as toluene, is particularly prevalent in adolescent populations and is considered to be a contributing factor to substance use and dependence later in life. While inhalants are often the initial "drug" experienced during this period, alcohol is another substance readily abused by adolescent populations. Although both substances are thought to have similar actions within the brain, our understanding of the implications of adolescent inhalant abuse upon subsequent exposure to alcohol remains to be investigated. Thus, this study aimed to assess locomotor responses to acute ethanol and voluntary ethanol consumption following a period of toluene inhalation throughout adolescence/early adulthood. Adolescent male Wistar rats (postnatal day [PN] 27) inhaled air or toluene (3000 ppm) for 1 h/day, 3 days/week for 4 (PN 27-52) or 8 weeks (PN 27-80) to mimic the patterns observed in human inhalant abusers. Following the exposure period, cross-sensitization to acute ethanol challenge (0.5 g/kg, intra-peritoneally [i.p.]), and voluntary consumption of 20% ethanol in a chronic intermittent 2-bottle choice paradigm, were assessed. Hepatic ethanol and acetaldehyde metabolism and liver histopathology were also investigated. Chronic intermittent toluene (CIT) exposure throughout adolescence for up to 8 weeks did not alter the behavioral response to acute ethanol or voluntary consumption of ethanol in adulthood, although an age-dependent effect on ethanol consumption was observed (p<0.05). Both liver function and pathology did not differ between treatment groups. Thus, in the paradigm employed, CIT exposure throughout adolescence and early adulthood did not predispose rats to subsequent locomotor sensitivity or voluntary consumption of ethanol in adulthood.
ItemSpecific impairments in instrumental learning following chronic intermittent toluene inhalation in adolescent ratsDick, ALW ; Axelsson, M ; Lawrence, AJ ; Duncan, JR (SPRINGER, 2014-04-01)RATIONALE: Inhalant abuse is prevalent in adolescent populations, with chronic use resulting in neurobiological and cognitive abnormalities in adulthood. However, the nature and persistence of cognitive dysfunction, particularly following adolescent inhalant abuse, remain equivocal. OBJECTIVE: The present study assessed specific cognitive processes beginning in late adolescence and adulthood following adolescent inhalation of toluene, a main component of many compounds readily abused. METHODS: Adolescent male Wistar rats (postnatal day (PN) 27) were exposed to chronic intermittent inhaled toluene (10,000 ppm) for 1 h/day, 3 days/week for 4 weeks (PN 27-52) to mimic the patterns observed in human adolescent inhalant abusers. Following toluene exposure, motor and cognitive function was assessed. RESULTS: Adolescent toluene exposure did not alter motor learning in the Rotarod task (PN 58) or acquisition, reversal, or retention of spatial learning in the Morris water maze (PN 55-64). In contrast, it delayed acquisition of instrumental responding for sucrose (5 % w/v) and impaired operant reversal learning and cue-induced reinstatement of sucrose seeking in adulthood (PN 57-100). CONCLUSION: This study demonstrates that exposure to toluene at an abuse concentration during adolescence results in specific impairments in aspects of instrumental learning, without altering motor function and spatial learning in late adolescence/early adulthood. Our data imply that persistent alterations in reward processing may occur following adolescent inhalant misuse.