Effects of nicotine-containing and “nicotine-free” e-cigarette refill liquids on intracranial self-stimulation in rats

Harris, Andrew C.; Muelken, Peter; Smethells, John R.; Yershova, Katrina; Stepanov, Irina; Olson, Thao T.; Kellar, Kenneth J.; LeSage, Mark

doi:10.1016/j.drugalcdep.2017.11.032

Cited by 19 publications

(25 citation statements)

References 60 publications

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“…Because nicotine's aversive effects can limit its abuse liability (e.g., [16,55,56]), this effect could potentially increase the primary reinforcing effects of this extract. While the current data do not support this account, they parallel our prior findings of the similar SA of EC liquids and nicotine alone, despite EC liquids producing attenuated aversive/anhedonic effects in an ICSS model [9,10,12]. There are numerous methodological factors that could account for this discrepancy across models, including nicotine dose, route and contingency.…”

Section: Discussioncontrasting

confidence: 67%

“…We previously found attenuated aversive/anhedonic effects of three different EC liquids compared to nicotine alone at a high dose of nicotine in an intracranial self-stimulation (ICSS) model [10,12]. The primary EC constituent propylene glycol (PG) also attenuated nicotine's acute ICSS threshold-elevating effects at PG concentrations similar to those in EC liquid doses used in our previous studies [15].…”

Section: Introductionmentioning

confidence: 65%

“…Animal models provide a critical tool for informing the FDA regulation of tobacco products, including ECs [7,8]. To this end, our lab has evaluated the effects of several EC liquids that contain nicotine and a range of EC constituents in preclinical addiction models [9][10][11][12]. This approach allows evaluation of the aggregate effects of these constituents on EC abuse liability.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of the Relative Abuse Liability of Electronic Cigarette Aerosol Extracts and Nicotine Alone in Adolescent Rats: A Behavioral Economic Analysis

Harris

Smethells

Palumbo

et al. 2020

IJERPH

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Background: Characterizing the determinants of the abuse liability of electronic cigarettes (ECs) in adolescents is needed to inform product regulation by the United States Food and Drug Administration (FDA). We recently reported that Vuse Menthol EC aerosol extract containing nicotine and a range of non-nicotine constituents (e.g., menthol, propylene glycol) had reduced aversive effects compared to nicotine alone in adolescent rats, whereas Aroma E-Juice EC aerosol extract did not. The current study used a behavioral economic approach to compare the relative abuse liability of these EC extracts and nicotine alone in an i.v. self-administration (SA) model in adolescents. Methods: Adolescents were tested for the SA of EC extracts prepared using an ethanol (ETOH) solvent or nicotine and saline, with and without 4% ETOH (i.e., the same concentration in the EC extracts) in 23 h/day sessions. Results. Although acquisition of SA was faster for nicotine + ETOH compared to all other formulations, the elasticity of demand for all nicotine-containing formulations was similar. Conclusions: EC aerosol extracts did not have greater abuse liability than nicotine alone in adolescents. These data suggest that nicotine may be the primary determinant of the abuse liability of these ECs in youth, at least in terms of the primary reinforcing effects of ECs mediated within the central nervous system.

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Section: Discussioncontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

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Comparison of the Relative Abuse Liability of Electronic Cigarette Aerosol Extracts and Nicotine Alone in Adolescent Rats: A Behavioral Economic Analysis

Harris

Smethells

Palumbo

et al. 2020

IJERPH

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“…Whatever the interpretation of these results, they show at least that the e-cigarette liquid contains active ingredients of constituents other than nicotine (according to ICSS measure). In order to understand the relative contribution of the central nervous system effects of nicotine components and nonnicotine components in the risk of the e-cigarette misuse, a study on a rat population showed the acute effects of electronic cigarette liquid on ICSS [19].…”

Section: Introductionmentioning

confidence: 99%

E-Cigarette Quality Control: Impurity and Nicotine Level Analysis in Electronic Cigarette Refill Liquids

Bennani¹,

Chentoufi²,

Karbane³

et al. 2020

The Scientific World Journal

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This work targets mainly the quality control of electronic cigarette liquids. It relies on an analytical control of a “32-product” sample made of several types of e-cigarette liquids taken from various supermarkets and tobacconist’s offices in Morocco. All along this study, we made sure to check both the conformity of the nicotine level indicated in the packaging of each product and the existence of any other components inside the product, especially toxic or unknown impurities. The method used for this study is known under the name of high-performance liquid chromatography. For statistical analysis, we used Student’s t-test for a single sample in order to analyze the relative differences between nicotine quantity reported in the product and the one measured during our experiment. Finally, we used linear regression test to determine the relationship between the nicotine level accuracy on the packaging and the level of toxic impurities in the products. The differences between the nicotine concentrations reported in the packages and the measured ones varied from −100% to +3.3%. The study showed that 31% of analyzed products have an accurate indication of the level of nicotine on the packaging. However, 47% of the studied products showed more than 20% difference between measure and packaging indication. In all analyzed samples, the level of impurities altered from 0 to 32.6%. Furthermore, the level of the nicotine breakdown products did not exceed 2% of the nicotine content in pretty much all of the samples. The actual nicotine content of electronic cigarette refill liquids is not always as precise as what is stated on the packaging; in addition to the level of impurities detected in several brands and that exceeds the European Pharmacopoeia standards, some may even present a risk of causing toxicological damage.

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“…A drug’s ICSS threshold-lowering and threshold-elevating effects may reflect its ability to enhance the reinforcing effects of non-drug stimuli and to produce aversion/anhedonia, respectively, two behavioral mechanisms mediating addiction (Caggiula et al, 2009; Chaudhri et al, 2006; Fowler and Kenny, 2014). We have suggested that nicotine’s ICSS threshold-elevating effects may also be related to nicotine toxicity (Harris et al, 2018; LeSage et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Propylene glycol, a major electronic cigarette constituent, attenuates the adverse effects of high-dose nicotine as measured by intracranial self-stimulation in rats

Harris

Muelken

Haave

et al. 2018

Drug and Alcohol Dependence

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Background: Non-nicotine tobacco constituents may contribute to the abuse liability of tobacco products. We previously reported that electronic cigarette (EC) refill liquids containing nicotine and a range of non-nicotine constituents attenuated the anhedonic/aversive effects of nicotine in an intracranial self-stimulation (ICSS) model. The alcohol propylene glycol (PG) is a primary ingredient in these and other EC liquids, yet its abuse potential has not been established. The goal of this study was to evaluate the effects of parenteral administration of PG alone and PG combined with nicotine on ICSS in rats. Methods and Results: PG alone did not affect ICSS at concentrations up to 100%. PG (25% or 60%) did not affect nicotine’s reinforcement-enhancing (ICSS threshold-decreasing) effects at low to moderate nicotine doses, but attenuated nicotine’s reinforcement-attenuating/aversive (ICSS threshold-increasing) effects at a high nicotine dose. PG concentrations similar to those in EC liquid doses used in our previous studies (1% or 3%) modestly attenuated the ICSS threshold-elevating effects of a high nicotine dose. Conclusions: PG attenuated elevations in ICSS thresholds induced by high-dose nicotine, which may reflect an attenuation of nicotine’s acute aversive/anhedonic and/or toxic effects. PG may have contributed to the attenuated ICSS threshold-elevating effects of EC liquids reported previously. Further examination of PG in models of addiction and toxicity is needed to understand the consequences of EC use and to inform the development of EC product standards by the FDA.

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Effects of nicotine-containing and “nicotine-free” e-cigarette refill liquids on intracranial self-stimulation in rats

Abstract: These findings suggest that non-nicotine constituents in these EC liquids do not contribute to their reinforcement-enhancing effects. However, they may attenuate nicotine's acute aversive/anhedonic and/or toxic effects, which may moderate the abuse liability and/or toxicity of ECs.

Cited by 19 publications

References 60 publications

Comparison of the Relative Abuse Liability of Electronic Cigarette Aerosol Extracts and Nicotine Alone in Adolescent Rats: A Behavioral Economic Analysis

Comparison of the Relative Abuse Liability of Electronic Cigarette Aerosol Extracts and Nicotine Alone in Adolescent Rats: A Behavioral Economic Analysis

E-Cigarette Quality Control: Impurity and Nicotine Level Analysis in Electronic Cigarette Refill Liquids

Propylene glycol, a major electronic cigarette constituent, attenuates the adverse effects of high-dose nicotine as measured by intracranial self-stimulation in rats

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