Early adolescent subchronic low-dose nicotine exposure increases subsequent cocaine and fentanyl self-administration in Sprague–Dawley rats

Abstract

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.

Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the CHRNA6 Gene

“…In addition, baseline and nicotine-induced DA release and nicotine-induced subsequent drug reinforcement (i.e., gateway hypothesis) and acquisition of other drugs of abuse should be assessed in the humanized CHRNA6 3′-UTR SNP rats. Using the 4-day nicotine exposure paradigm, studies have shown nicotine enhances subsequent cocaine [ 36 , 56 , 57 , 58 ], methamphetamine [ 56 , 59 ], ethanol [ 56 ], and fentanyl intake [ 58 , 60 , 61 ]. Furthermore, nicotine potency and efficacy may be shifted in the humanized CHRNA6 3′-UTR SNP rodents, and future studies should implement a dose–response curve.…”

Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice

“…Previous literature has investigated rodent models of opioid dependence, including morphine (47)(48)(49), oxycodone (10,12,50,51), heroin (6,(52)(53)(54), remifentanil (34,(55)(56)(57)(58), and fentanyl (24,33,36,38,(59)(60)(61)(62)(63)(64)(65)(66), using various routes of administration, with the majority of studies done in rats. IVSA of fentanyl has been widely studied in rats (24,25,(59)(60)(61)(62)(67)(68)(69)(70)(71), with findings demonstrating mixed results on the development of dependence and withdrawal signs. One previous study reported that rats undergoing 14 days IVSA of fentanyl for 6 hours per day maintained a consistent rate of self-administration (62).…”

Facilitation of the mental health of adolescents abusing substances: A concept analysis

“…Some effort towards intervening in this challenge, focussing on mental health promotion and substance abuse prevention was made, yet it appears it was not enough (Steel et al 2020 ; World Health Organization [WHO] 2020 ). There are some shortfalls in these interventions as there is no satisfying improvement related to this phenomenon; instead, the prevalence of substance abuse is becoming worse each day (Cardenas et al 2021 ; Setlalentoa, Ryke & Strydom 2016 ) Findings from the researcher’s minor dissertation (Rikhotso 2008 ) indicate that adolescents who abuse substances experience a range of emotional, physical, academic, and social setbacks and challenges.…”

“…These called for holistic, multi-level and multi-sectoral interventions for all role-players, such as government departments, non-governmental organisations, the community, and faith-based organisations (Setlalentoa et al 2016 ). Moreover, (Gallop et al 2020 ) recommendations to reduce adolescent substance abuse included (Rikhotso 2008 ) health promotion activities, programmes, and services; (WHO 2020 ) constructive media-based public education campaigns; (Steel et al 2020 ) development and implementation of school-based substance abuse programmes; and (Cardenas et al 2021 ) provision of recreational facilities.…”