Andrew C Harris1, Peter Muelken2, Zach Haave3, Yayi Swain4, John R Smethells5, Mark G LeSage6. 1. Hennepin Healthcare Research Institute, 701 Park Avenue, Minneapolis, MN USA; Departments of Medicine, University of Minnesota Medical School, Variety Club Research Center (VCRC), 401 East River Parkway, 1(st) Floor - Suite 131, Minneapolis, MN 55455, USA; Departments of Psychology, University of Minnesota Medical School, N218 Elliott Hall, 75 E River Rd, Minneapolis, MN 55455, USA. Electronic address: harr0547@umn.edu. 2. Hennepin Healthcare Research Institute, 701 Park Avenue, Minneapolis, MN USA. 3. Hennepin Healthcare Research Institute, 701 Park Avenue, Minneapolis, MN USA; Departments of Neuroscience, University of Minnesota Medical School, 6-145 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA. 4. Hennepin Healthcare Research Institute, 701 Park Avenue, Minneapolis, MN USA; Departments of Psychology, University of Minnesota Medical School, N218 Elliott Hall, 75 E River Rd, Minneapolis, MN 55455, USA. 5. Hennepin Healthcare Research Institute, 701 Park Avenue, Minneapolis, MN USA; Departments of Psychiatry, University of Minnesota Medical School, Fairview Riverside West Building, 2312 S. 6th St., Floor 2, Suite F-275, Minneapolis, MN 55454, USA. 6. Hennepin Healthcare Research Institute, 701 Park Avenue, Minneapolis, MN USA; Departments of Medicine, University of Minnesota Medical School, Variety Club Research Center (VCRC), 401 East River Parkway, 1(st) Floor - Suite 131, Minneapolis, MN 55455, USA; Departments of Psychology, University of Minnesota Medical School, N218 Elliott Hall, 75 E River Rd, Minneapolis, MN 55455, USA.
Abstract
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.
BACKGROUND: Non-nicotinetobacco 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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