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Sex differences in yohimbine-induced increases in the reinforcing efficacy of nicotine in adolescent rats

Authors

  • Sophia Li,

    1. Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada
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  • Sheng Zou,

    1. Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada
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  • Kathleen Coen,

    1. Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada
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  • Douglas Funk,

    1. Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada
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  • Megan J. Shram,

    1. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
    2. INC Research Early Stage, Toronto, ON, Canada
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  • A.D. Lê

    Corresponding author
    1. Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
    3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada
    • Correspondence to: A.D. Lê, Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada. E-mail: Anh_Le@camh.net

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Abstract

Stress is an important factor in the initiation and maintenance of smoking in adolescents. Women are more vulnerable to the development of addiction to smoking and have more difficulty quitting than men. Women also showe enhanced responses to stress. Despite these differences, no work has been done examining the effects of stress on the reinforcing efficacy of self-administered nicotine in adolescent rats, or if there are sex differences. Male and female adolescent Long Evans rats were trained to self-administer one of three different intravenous doses of nicotine (7.5, 15, 30 μg/kg/infusion) first on fixed ratio, and then on a progressive ratio (PR) schedule beginning on postnatal day 33. The effect of the pharmacological stressor yohimbine (0.3, 0.6 mg/kg, i.p.) on the reinforcing efficacy of nicotine was then determined using the PR schedule. Yohimbine stimulated nicotine intake and increased PR breakpoints and numbers of infusions received in both male and female adolescent rats. The infusion dose of nicotine was positively associated with yohimbine-induced increases in responding. Female rats showed significantly increased breakpoints at yohimbine doses and nicotine infusion doses at which males did not. The effects of the pharmacological stressor, yohimbine on the reinforcing efficacy of nicotine are therefore linked to sex and nicotine infusion dose. Female rats are more sensitive to stress-induced potentiation of nicotine self-administration.

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