Mehrak Javadi-Paydar1, Tony M Kerr1, Eric L Harvey1, Maury Cole2, Michael A Taffe3. 1. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA. 2. La Jolla Alcohol Research, Inc., La Jolla, CA, USA. 3. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: mtaffe@scripps.edu.
Abstract
BACKGROUND: Electronic nicotine delivery systems (ENDS, e-cigarettes) are increasingly used for the self-administration of nicotine by various human populations, including previously nonsmoking adolescents. Studies in preclinical models are necessary to evaluate health impacts of ENDS including the development of nicotine addiction, effects of ENDS vehicles, flavorants and co-administered psychoactive substances such as Δ9-tetrahydrocannabinol (THC). This study was conducted to validate a rat model useful for the study of nicotine effects delivered by inhalation of vapor created by ENDS. METHODS: Male Sprague-Dawley rats (N = 8) were prepared with radio telemetry devices for the reporting of temperature and activity. Experiments subjected rats to inhalation of vapor generated by an electronic nicotine delivery system (ENDS) adapted for rodents. Inhalation conditions included vapor generated by the propylene glycol (PG) vehicle, Nicotine (1, 10, 30 mg/mL in the PG) and THC (12.5, 25 mg/mL). RESULTS: Nicotine inhalation increased spontaneous locomotion and decreased body temperature of rats. Pretreatment with the nicotinic cholinergic receptor antagonist mecamylamine (2 mg/kg, i.p.) prevented stimulant effects of nicotine vapor inhalation and attenuated the hypothermic response. Combined inhalation of nicotine and THC resulted in apparently independent effects which were either additive (hypothermia) or opposed (activity). CONCLUSIONS: These studies provide evidence that ENDS delivery of nicotine via inhalation results in nicotine-typical effects on spontaneous locomotion and thermoregulation in male rats. Effects were blocked by a nicotinic antagonist, demonstrating mechanistic specificity. This system will therefore support additional studies of the contribution of atomizer/wick design, vehicle constituents and/or flavorants to the effects of nicotine administered by ENDS.
BACKGROUND: Electronic nicotine delivery systems (ENDS, e-cigarettes) are increasingly used for the self-administration of nicotine by various human populations, including previously nonsmoking adolescents. Studies in preclinical models are necessary to evaluate health impacts of ENDS including the development of nicotine addiction, effects of ENDS vehicles, flavorants and co-administered psychoactive substances such as Δ9-tetrahydrocannabinol (THC). This study was conducted to validate a rat model useful for the study of nicotine effects delivered by inhalation of vapor created by ENDS. METHODS: Male Sprague-Dawley rats (N = 8) were prepared with radio telemetry devices for the reporting of temperature and activity. Experiments subjected rats to inhalation of vapor generated by an electronic nicotine delivery system (ENDS) adapted for rodents. Inhalation conditions included vapor generated by the propylene glycol (PG) vehicle, Nicotine (1, 10, 30 mg/mL in the PG) and THC (12.5, 25 mg/mL). RESULTS:Nicotine inhalation increased spontaneous locomotion and decreased body temperature of rats. Pretreatment with the nicotinic cholinergic receptor antagonist mecamylamine (2 mg/kg, i.p.) prevented stimulant effects of nicotine vapor inhalation and attenuated the hypothermic response. Combined inhalation of nicotine and THC resulted in apparently independent effects which were either additive (hypothermia) or opposed (activity). CONCLUSIONS: These studies provide evidence that ENDS delivery of nicotine via inhalation results in nicotine-typical effects on spontaneous locomotion and thermoregulation in male rats. Effects were blocked by a nicotinic antagonist, demonstrating mechanistic specificity. This system will therefore support additional studies of the contribution of atomizer/wick design, vehicle constituents and/or flavorants to the effects of nicotine administered by ENDS.
Authors: Claire Adams Spears; Dina M Jones; Scott R Weaver; Terry F Pechacek; Michael P Eriksen Journal: Addict Behav Date: 2018-01-16 Impact factor: 3.913
Authors: Matthew E Eggers; Youn O Lee; Kyle Jackson; Jenny L Wiley; Lauren Porter; James M Nonnemaker Journal: Addict Behav Date: 2017-02-10 Impact factor: 3.913
Authors: Janaina C M Vendruscolo; Brendan J Tunstall; Stephanie A Carmack; Brooke E Schmeichel; Emily G Lowery-Gionta; Maury Cole; Olivier George; Sophia A Vandewater; Michael A Taffe; George F Koob; Leandro F Vendruscolo Journal: Neuropsychopharmacology Date: 2017-08-16 Impact factor: 7.853
Authors: J D Nguyen; P T Bremer; C S Hwang; S A Vandewater; K C Collins; K M Creehan; K D Janda; M A Taffe Journal: Drug Alcohol Depend Date: 2017-04-14 Impact factor: 4.492
Authors: Kim A G J Romijnders; Liesbeth van Osch; Hein de Vries; Reinskje Talhout Journal: Int J Environ Res Public Health Date: 2018-06-06 Impact factor: 3.390
Authors: Christian Montanari; Leslie K Kelley; Tony M Kerr; Maury Cole; Nicholas W Gilpin Journal: Psychopharmacology (Berl) Date: 2019-11-23 Impact factor: 4.530
Authors: Cristina Miliano; E Reilly Scott; Laura B Murdaugh; Emma R Gnatowski; Christine L Faunce; Megan S Anderson; Malissa M Reyes; Ann M Gregus; Matthew W Buczynski Journal: J Neurosci Methods Date: 2019-10-12 Impact factor: 2.390
Authors: Jacques D Nguyen; Yanabel Grant; Kevin M Creehan; Candy S Hwang; Sophia A Vandewater; Kim D Janda; Maury Cole; Michael A Taffe Journal: Neuropharmacology Date: 2019-04-11 Impact factor: 5.250