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Specific impairments in instrumental learning following chronic intermittent toluene inhalation in adolescent rats

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Abstract

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.

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Acknowledgments

The authors would like to thank Ms. Zakia Haque for assistance with running animals through the inhalant exposure paradigm. This study was supported by The National Health and Medical Research Council of Australia of which AJL is a Principal Research Fellow (1020737), the Australian Research Council (DP 110100379) of which JRD is a Future Fellow (100100235) and the Victorian Government's Operational Infrastructure Support Scheme.

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Authors and Affiliations

  1. Florey Institute of Neuroscience and Mental Health, University of Melbourne, L3, Kenneth Myer Building, Cnr Genetics Lane on Royal Parade, Parkville, Melbourne, Victoria, 3010, Australia

    Alec L. W. Dick, Martin Axelsson, Andrew J. Lawrence & Jhodie R. Duncan

  2. Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Melbourne, Victoria, 3010, Australia

    Alec L. W. Dick & Andrew J. Lawrence

  3. Department Anatomy and Neuroscience, University of Melbourne, Parkville, Melbourne, Victoria, 3010, Australia

    Jhodie R. Duncan

  4. Department of Applied Psychology, Royal Melbourne University of Technology, Melbourne, Victoria, 3000, Australia

    Martin Axelsson

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  1. Alec L. W. Dick
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  2. Martin Axelsson
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  4. Jhodie R. Duncan
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Correspondence to Andrew J. Lawrence or Jhodie R. Duncan.

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Dick, A.L.W., Axelsson, M., Lawrence, A.J. et al. Specific impairments in instrumental learning following chronic intermittent toluene inhalation in adolescent rats. Psychopharmacology 231, 1531–1542 (2014). https://doi.org/10.1007/s00213-013-3363-7

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  • DOI: https://doi.org/10.1007/s00213-013-3363-7

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