Early adolescent subchronic low-dose nicotine exposure increases subsequent cocaine and fentanyl self-administration in Sprague–Dawley rats
Open accessAbstract
An exponential rise in nicotine-containing electronic-cigarette use has been observed during the period of adolescence. Preclinical studies have shown that nicotine exposure during early adolescence, but not adulthood, increases subsequent drug intake and reward. Although growing clinical trends highlight that stimulant use disorders are associated with the opioid epidemic, very few studies have assessed the effects of adolescent nicotine exposure on opioid intake. The objective of our current study is to develop a new animal model to assess the causal relationship of adolescent nicotine exposure on subsequent opioid intake. In this effort, we first replicate previous studies using a well-established 4-day nicotine paradigm. Rats are pretreated with a low dose of nicotine (2 × , 30 μg/kg/0.1 mL, intravenous) or saline during early adolescence (postnatal days 28-31) or adulthood (postnatal days 86-89). Following nicotine pretreatment on postnatal day 32 or postnatal day 90, animals underwent operant intravenous self-administration for the psychostimulant, cocaine [500 μg/kg/infusion (inf)] or the opioid, fentanyl (2.5 μg/kg/inf). We successfully show that adolescent but not adult, nicotine exposure enhances cocaine self-administration in male rats. Furthermore, we illustrate early adolescent but not adult nicotine exposure enhances fentanyl self-administration, independent of sex. Overall, our findings highlight that adolescence is a unique period of development that is vulnerable to nicotine-induced enhancement for cocaine and fentanyl self-administration in rats.
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Brief pretreatment of early adolescent rats (P28-31) with a low dose of nicotine that models smoking initiation significantly increases self-administration of cocaine, ethanol, fentanyl, and methamphetamine when compared to adults.
“Brief pretreatment of early adolescent rats (postnatal days (P) 28–31) with a low dose of nicotine that models smoking initiation significantly increases self-administration of cocaine, ethanol, fentanyl, and methamphetamine when compared to adults [146–151].”
From Nicotine on the developing brain. (2023) · cites this paper as [150]
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- Authors
- Cardenas, A., Martinez, M., Saenz Mejia, A., & Lotfipour, S.
- Affiliations
- Department of Pharmaceutical Sciences
- Department of Psychological Sciences
- Department of Biological Sciences
- University of California, Irvine (US)
- Corresponding author
- Lotfipour, Shahrdad
- Venue
- Behavioural Pharmacology
- Published
- 2020-09-21
- Volume
- 32
- Issue
- 1
- Pages
- 86-91
- ISSN
- 0955-8810 (ISSN-L)
- PMC
- PMC7790845
- OpenAlex
- W3089067637
- Cited by
- 21
- References
- 48
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 2
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR001414)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- adolescent nicotine exposure, cocaine self-administration, fentanyl self-administration, stimulant use disorder, opioid epidemic, electronic cigarettes, nicotine sensitization, sex differences
- MeSH terms
- Age Factors, Animals, Cocaine, Dose-Response Relationship, Drug, Female, Fentanyl, Male, Nicotine, Self Administration, Sex Factors, Rats, Sprague-Dawley, Rats
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