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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    817—Amphetamine and Related Drugs: Neural Mechanisms of Addiction

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    817.11: Effect of adolescent and adult nicotine exposure on methamphetamine self-administration in male rats

    Location: Halls B-H

    1Dept. of Psychology, California State Univ., San Bernardino, CA; 2Psychology, California State Long Beach, Long Beach, CA

    Abstract Body: Nicotine is a commonly abused substance among adolescents and is believed to be a “gateway” to other drugs of abuse. In support of the gateway hypothesis, cigarette smoking during adolescence is related to increased methamphetamine (METH) use in adulthood. However, it is difficult to understand the exact relationship between early use of nicotine and later METH use because the majority of juvenile smokers continue to smoke cigarettes as adults. Thus, the present investigation sought to determine the individual and combined contribution of adolescent and adult nicotine exposure on METH self-administration and METH-seeking behavior in male rats. A total of 43 male rats of Sprague-Dawley descent were pretreated with saline or nicotine (0.16 or 0.64 mg/kg, sc) from postnatal day (PD) 35-50. On PD 51, rats in in the 0.16 and 0.64 pretreatment groups were evenly divided and assigned to a group that either continued to receive the same nicotine dose they received as adolescents or saline. Rats that had received saline as adolescents continued to receive saline injections. Thus, there were five groups in this experiment based on adolescent/adult nicotine exposure (SAL/SAL, 0.16/0.16, 0.16/SAL, 0.64/0.64, and 0.64/SAL). On PD 60, rats were trained to press a lever reinforced with sucrose and then implanted with a jugular catheter. After a five day recovery period, rats were trained to self-administer METH (0.05 mg/kg) on a FR1 schedule, followed by an additional seven days on a FR3 schedule. Rats then underwent a 14-day extinction period, during which lever presses had no scheduled consequences. Subsequently, METH-seeking behavior (i.e., lever presses without METH reinforcement) was assessed after a METH-priming injection METH (1 mg/kg, ip). Rats given the low dose of nicotine during both the adolescent pretreatment phase and during adulthood (e.g., 0.16/0.16 group) obtained more METH infusions and had more active lever presses than rats in the SAL/SAL group. In contrast, the group receiving 0.16 nicotine and saline as adults (0.16/SAL) or the groups that received the higher dose of nicotine (0.64/0.64; 0.64/SAL) did not show this enhancement. Interestingly neither nicotine pretreatment nor nicotine during adulthood had a significant effect on the extinction or drug-primed reinstatement of METH-seeking behavior. Taken together these data suggest that extended causal use of nicotine enhances the reinforcing effects of METH while heavier exposure has no effect on METH use.

    Lay Language Summary: Using an animal model, the present
    preliminary investigation found that repeated exposure to low amounts of
    nicotine during adolescence and adulthood significantly increased
    methamphetamine intake. Interestingly,
    exposure to a higher dose of nicotine did not affect methamphetamine use.
    Our results are consistent with
    previous human and animal studies showing that nicotine exposure during
    adolescence is associated with increased methamphetamine use in adulthood. Importantly, our results extend past findings
    by demonstrating that continued use of nicotine after adolescence increases
    methamphetamine intake more than adolescent exposure alone. These finding are potentially relevant to
    the human condition because: (1) the majority of juvenile smokers continue to
    smoke as adults, and (2) methamphetamine users have very high rates of smoking
    (87-92% vs. 22% for the general population).
    To determine the effects of
    adolescent and adult nicotine exposure on methamphetamine intake, we injected 43
    male albino rats with distilled water or nicotine (0.16 or 0.64 mg/kg) from
    postnatal day 35-50 (an age period roughly analogous to human adolescence). On postnatal
    day 51, rats previously receiving nicotine were assigned to
    groups that either continued to receive the same nicotine dose or distilled
    water throughout the experiment. Rats that received water as adolescents
    continued to receive water injections. On postnatal day 60 (early adulthood),
    all rats were trained to press a lever for an intravenous methamphetamine infusion.
    After the rats learned to reliably press the lever for methamphetamine, we assessed how long it would
    take the rats to stop pressing the lever if no drug reinforcement was given
    (i.e., extinction training). Afterwards,
    we measured what effect re-exposure to methamphetamine (also called priming)
    would have on lever pressing. Extinction
    training was used to measure the overall motivation to use methamphetamine,
    while methamphetamine re-exposure was used as a measure of relapse.
    Our study revealed that rats given 0.16
    mg/kg nicotine during both adolescence and adulthood earned a greater numbers
    of methamphetamine infusions and pressed the lever more than rats that received
    (1) a higher dose (0.64 mg/kg) of nicotine, (2) 0.16 mg/kg nicotine during
    adolescence only, or (3) water during adolescence and adulthood. Interestingly,
    we found that nicotine exposure did not affect the number of days to extinguish
    lever pressing or the number of lever presses made after methamphetamine
    Taken together, our data show that
    extended casual (i.e., low dose) use of nicotine enhances the reinforcing
    effects of methamphetamine, while heavier exposure has no effect on methamphetamine
    intake. The next step in this
    investigation will be to more precisely determine how age interacts with the
    amount of nicotine exposure to affect methamphetamine intake. In this regard, sex differences will be of
    particular interest because previous studies found that females are more
    vulnerable to the reinforcing effects of both nicotine and
    methamphetamine. It is possible, therefore,
    that nicotine exposure will have a greater effect on methamphetamine intake in
    female rats.
    Importantly, these data suggest that nicotine
    use is a critical factor to consider when treating methamphetamine addiction. Obtaining detailed information about a
    patient’s past and present nicotine usage may be a key component when designing
    a successful treatment plan for methamphetamine abusers.