Effects of nicotine conditioning history on alcohol and methamphetamine self-administration in rats

Abstract

Background.-Smoking constitutes a significant public health risk. Alcohol and methamphetamine use disorders are also highly co-morbid with smoking, further increasing negative health outcomes. An important question in determining the underlying neurobiology of nicotine poly-drug use is understanding whether having a positive history with nicotine effects alters later drug-taking behavior. Methods.-The current experiments sought to elucidate whether having an appetitive nicotine conditioning history would affect later alcohol or methamphetamine self-administration. Adult male and female Long-Evans rats were first trained on a discriminated goal-tracking task in which the interoceptive effects of nicotine predicted sucrose reinforcement. As a control, pseudoconditioned groups were included that had equated nicotine and sucrose experience. Rats were then shifted to either alcohol self-administration or methamphetamine self-administration. Results.-Nicotine conditioning history had no effect on acquisition or maintenance of alcohol self-administration in males or females. In contrast, an appetitive nicotine conditioning history decreased methamphetamine self-administration in female rats, but not males. Conclusions.-In female, but not male rats, an appetitive conditioning history with nicotine decreases methamphetamine, but not alcohol, self-administration. This dissociation suggests that the effects may be due to a specific increase in the reinforcing value of methamphetamine. This Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Age- and Sex-Dependent Nicotine Pretreatment Effects on the Enhancement of Methamphetamine Self-administration in Sprague-Dawley Rats

“…5,6,19,43 For adults, clinical and preclinical studies show that female adults are more sensitive to nicotine, than males. 44,45 While studies have shown nicotine conditioning decreases METH self-administration in female rats, 45 we observe nicotine-induced discrimination between reinforced and nonreinforced responding after day 3 of selfadministration and overall METH intake (mg/kg) in female adults. Conversely, low-dose nicotine exposure had no effect on METH selfadministration in male adults.…”

Considering Drug-Associated Contexts in Substance Use Disorders and Treatment Development

“…Supporting the latter idea, animal models such as the "discriminated goal-tracking task" show that drug interoceptive stimuli can readily guide reward-seeking behavior [22,[96][97][98][99]. In these studies, the experimenter administers either a drug (e.g., nicotine) or vehicle (e.g., saline) prior to daily conditioning sessions.…”