Adolescence is a vulnerable developmental period in regards to drug initiation and use. The gateway hypothesis suggests that adolescent cigarette smoking may result in a heightened risk for methamphetamine use. However, little is understood about the role of nicotine on adolescent methamphetamine addiction. The aim of the present study was to determine whether early, late, or continuous adolescent nicotine exposure would alter oral methamphetamine self-administration, extinction, or reinstatement. A total of 164 male and female Sprague-Dawley rats were pretreated with saline or nicotine (0.16, or 0.64 mg/kg, sc) beginning on postnatal day (PD) 25 for 10 consecutive days. On PD 35, rats in the 0.16 and 0.64 mg/kg 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 were divided into three equal groups, where they received 0.16 or 0.64 mg/kg nicotine or continued to receive saline injections. Drug treatments starting on PD 35 continued until the end of the experiment. Thus, there were a total of 7 groups: SAL–SAL, 0.16–0.16, 0.16–SAL, SAL-0.16, 0.64–0.64, 0.64–SAL, SAL-0.64. On PD 35, all rats began nose poke training. Rats were exposed to a methamphetamine fade in, sucrose fade out procedure across 5 different methamphetamine-sucrose combinations. This procedure resulted in exposure to a 40 mg/l methamphetamine solution for 3 consecutive days on a FR2 schedule. Following the last day of methamphetamine self-administration, rats were exposed to extinction training. Once the extinction criteria were met, rats were given a priming injection of methamphetamine (1.0 mg/kg, ip). Data from the present investigation revealed two main important findings: a) acquisition of oral methamphetamine self-administration can be attained in adolescent rats; and b) adolescent nicotine exposure differentially alters oral methamphetamine self-administration. Exposure to a low dose of nicotine (0.16 mg/kg), but not a high dose of nicotine (0.64 mg/kg), attenuated consumption and responding for methamphetamine during self-administration. During the extinction and reinstatement periods, we found that nicotine (0.16 or 0.64 mg/kg) exposure did not alter consumption or responding for methamphetamine. Female rats showed augmented total active nose pokes and active nose pokes within the reinforcement period compared to male rats. Conversely, male rats showed augmented sucrose and methamphetamine solution consumption across methamphetamine acquisition sessions 1–6. These data suggest that for adolescents who already present moderate cigarette smoking behavior at the time of methamphetamine cessation treatment, total abstinence from both nicotine and methamphetamine may be a less effective form of treatment. It may be clinically beneficial to first treat the methamphetamine addiction, and subsequently treat the nicotine addiction. Regardless of the method of treatment for adolescent methamphetamine addiction, nicotine exposure should be closely monitored.
Identifer | oai:union.ndltd.org:csusb.edu/oai:scholarworks.lib.csusb.edu:etd-1676 |
Date | 01 December 2017 |
Creators | Harmony, Zachary Robert |
Publisher | CSUSB ScholarWorks |
Source Sets | California State University San Bernardino |
Detected Language | English |
Type | text |
Format | application/pdf |
Source | Electronic Theses, Projects, and Dissertations |
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