Delivery of nicotine aerosol to mice via a modified electronic cigarette device.
Although both men and women use e-cigarettes, most preclinical nicotine research has focused on its effects in male rodents following injection. The goals of the present study were to develop an effective e-cigarette nicotine delivery system, to compare results to those obtained after subcutaneous (s.c.) injection, and to examine sex differences in the model.



Hypothermia and locomotor suppression were assessed following aerosol exposure or s.c. injection with nicotine in female and male mice. Subsequently, plasma and brain concentrations of nicotine and cotinine were measured.



Passive exposure to nicotine aerosol produced concentration-dependent and mecamylamine reversible hypothermic and locomotor suppressant effects in female and male mice, as did s.c. nicotine injection. In plasma and brain, nicotine and cotinine concentrations showed dose/concentration-dependent increases in both sexes following each route of administration. Sex differences in nicotine-induced hypothermia were dependent upon route of administration, with females showing greater hypothermia following aerosol exposure and males showing greater hypothermia following injection. In contrast, when they occurred, sex differences in nicotine and cotinine levels in brain and plasma consistently showed greater concentrations in females than males, regardless of route of administration.



In summary, the e-cigarette exposure device described herein was used successfully to deliver pharmacologically active doses of nicotine to female and male mice. Further, plasma nicotine concentrations following exposure were similar to those after s.c. injection with nicotine and within the range observed in human smokers. Future research on vaped products can be strengthened by inclusion of translationally relevant routes of administration.
RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States.
Timothy W
TW
Lefever
RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States.
Youn O K
YO
Lee
RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States.
Alexander L
AL
Kovach
RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States.
Melanie A R
MA
Silinski
RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States.
Julie A
JA
Marusich
RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States.
Brian F
BF
Thomas
RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, United States. Electronic address: jwiley@rti.org.
Jenny L
JL
Wiley
D000336:Aerosols; D000818:Animals; D001921:Brain / Q000378:metabolism; D003367:Cotinine / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D066300:Electronic Nicotine Delivery Systems; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity; D009538:Nicotine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018733:Nicotinic Antagonists / Q000494:pharmacology; D012727:Sex Characteristics
D000336:Aerosols; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine; D003367:Cotinine
Cotinine; Electronic cigarette; Metabolism; Nicotine; Sex differences