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Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction

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Abstract

Rationale

Enhanced reinforcing effects of nicotine during adolescence appear to contribute to the rapid development of dependence in this age group. However, the contribution of nicotine withdrawal to dependence in adolescents is unclear.

Objective

We compared motivational and somatic signs of nicotine withdrawal in adolescent and adult rats.

Materials and methods

In experiment 1, motivational signs of nicotine withdrawal were compared using intracranial self-stimulation procedures after administration of mecamylamine (1.5 mg/kg, i.p.) in adolescent and adult rats made dependent on nicotine (9 mg/kg/day). Somatic signs of withdrawal were compared in two experiments using various doses of nicotine (adolescent doses: 0, 1.6, 3.2, 4.7 mg/kg/day; adult doses: 0, 1, 2.1, 3.2 mg/kg/day, expressed as nicotine base) to produce dependence and one dose of mecamylamine (1.5 mg/kg, i.p.) to precipitate withdrawal (experiment 2) and in a subsequent experiment, using various doses of mecamylamine (0, 0.75, 1.5, 3.0 mg/kg, i.p.) to precipitate withdrawal and a dose of nicotine (adolescent dose: 4.7 mg/kg/day; adult dose: 3.2 mg/kg/day) that produced equivalent nicotine blood levels in these age groups (experiment 3).

Results

Adolescents did not display the decreases in brain reward function observed in adults experiencing withdrawal, and displayed fewer somatic signs of nicotine withdrawal relative to adults regardless of the dosing procedure used.

Conclusion

The negative effects of nicotine withdrawal are lower during adolescence relative to later periods of development. Both the enhanced rewarding effects and the diminished nicotine withdrawal likely contribute to the rapid development of nicotine use during adolescence.

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Acknowledgements

This research was supported by the Robert Wood Johnson Foundation Tobacco Etiology Research Network, the California Tobacco-Related Disease Research Program (11FT-0112 to AWB, 12RT-0099 to GFK, and 12RT-0231 to AM), and the National Institute on Drug Abuse (DA11946 to AM). The authors thank Mr. Michael Arrends for his excellent editorial assistance and Yanabel Grant for her technical assistance. This is publication number 16665-NP from The Scripps Research Institute.

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Authors and Affiliations

  1. Molecular and Integrative Neuroscience Department, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Laura E. O’Dell, Adie W. Bruijnzeel, Ron T. Smith, Loren H. Parsons, Heather N. Richardson, George F. Koob & Athina Markou

  2. Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainsville, FL, 32608, USA

    Michele L. Merves & Bruce A. Goldberger

  3. Department of Psychology, The University of Texas at El Paso, El Paso, TX, 79968, USA

    Laura E. O’Dell

  4. Department of Psychiatry, University of Florida, Gainsville, FL, 32608, USA

    Adie W. Bruijnzeel

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  1. Laura E. O’Dell
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  2. Adie W. Bruijnzeel
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  3. Ron T. Smith
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  4. Loren H. Parsons
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  5. Michele L. Merves
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  6. Bruce A. Goldberger
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  7. Heather N. Richardson
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  8. George F. Koob
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  9. Athina Markou
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Correspondence to George F. Koob.

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O’Dell, L.E., Bruijnzeel, A.W., Smith, R.T. et al. Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction. Psychopharmacology 186, 612–619 (2006). https://doi.org/10.1007/s00213-006-0383-6

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  • DOI: https://doi.org/10.1007/s00213-006-0383-6

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