Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats

Psychopharmacology (Berl). 2020 Mar;237(3):613-625. doi: 10.1007/s00213-019-05400-2. Epub 2019 Nov 23.


Rationale: Non-contingent chronic nicotine exposure procedures have evolved rapidly in recent years, culminating in electronic nicotine delivery systems (ENDS or e-cigarettes) to deliver vaporized drugs to rodents in standard housing chambers.

Objectives: The aim of the current work was to use ENDS to test concentration-dependent effects of nicotine e-cigarette vapor inhalation on blood-nicotine concentrations, blood-cotinine concentrations, and somatic withdrawal signs over time in rats.

Methods: Male Wistar rats were exposed to vapor containing various concentrations of nicotine (20, 40, 80 mg/mL) for 11 days through ENDS, and blood concentrations of nicotine and cotinine, the major proximate metabolite of nicotine, as well as spontaneous and precipitated somatic withdrawal signs, were measured over time (across days of exposure and over hours after termination of vapor exposure).

Results: Exposing male Wistar rats to non-contingent nicotine vapor inhalation through ENDS produces somatic withdrawal symptoms and measurable blood-nicotine and blood-cotinine levels that change according to (1) concentration of nicotine in vape solution, (2) number of days of nicotine vapor exposure, (3) time since termination of nicotine vapor exposure, and (4) relative to the withdrawal signs, whether withdrawal was spontaneous or precipitated (by mecamylamine).

Conclusions: The data presented here provide parameters that can be used as a reasonable starting point for future work that employs ENDS to deliver non-contingent nicotine vapor in rats, although many parameters can and should be altered to match the specific goals of future work.

Keywords: Addiction; E-cigarette; ENDS; Nicotine; Vape; Withdrawal.

MeSH terms

  • Administration, Inhalation
  • Age Factors
  • Animals
  • Atmosphere Exposure Chambers / adverse effects
  • Cotinine / blood*
  • Dose-Response Relationship, Drug
  • Electronic Nicotine Delivery Systems*
  • Male
  • Medically Unexplained Symptoms
  • Nicotine / administration & dosage*
  • Nicotine / blood*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Substance Withdrawal Syndrome / blood*
  • Substance Withdrawal Syndrome / psychology
  • Vaping / adverse effects
  • Vaping / blood*
  • Vaping / psychology


  • Nicotine
  • Cotinine