Nicotine reinforcement in never-smokers.
BACKGROUND
Global tobacco-related mortality dwarfs that of all other drugs. Nicotine is believed to be the primary agent responsible for tobacco use and addiction. However, nicotine is a relatively weak and inconsistent reinforcer in nonhumans and nicotine reinforcement has not been demonstrated in never-smokers.


OBJECTIVE
This study investigated the discriminative, subjective, and reinforcing effects of nicotine in never-smokers.


METHODS
Eighteen never-smokers (< 50 lifetime nicotine exposures) participated in a double-blind study. During a drug discrimination phase, volunteers ingested oral nicotine and placebo capsules (quasi-random order) at least 2 h apart and rated subjective effects repeatedly for 2 h after ingestion in daily sessions. Blocks of 10 sessions were continued until significant discrimination was achieved (p ≤ 0.05, binomial test; ≥ 8 of 10). Following discrimination, nicotine choice was tested by having volunteers choose which capsule set to ingest on each daily session. Successive blocks of 10 sessions were conducted until choice for nicotine or placebo met significance within each volunteer (≥ 8 of 10 sessions).


RESULTS
All 18 volunteers significantly discriminated nicotine from placebo; the lowest dose discriminated ranged from 1.0 to 4.0 mg/70 kg. Nine volunteers significantly chose nicotine (choosers) and nine significantly chose placebo (nicotine avoiders). The choosers reported predominately positive nicotine subjective effects (e.g., alert/attentive, good effects, liking), while avoiders tended to report negative effects (e.g., dizzy, upset stomach, disliking). Both choosers and avoiders attributed their choice to the qualitative nature of drug effects.


CONCLUSIONS
These results provide the first evidence that nicotine can function as a reinforcer in some never-smokers.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224-6823, USA.
Angela N
AN
Duke
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224-6823, USA.
Matthew W
MW
Johnson
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224-6823, USA.
Chad J
CJ
Reissig
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224-6823, USA. rgriff@jhmi.edu.|Department of Neuroscience, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224-6823, USA. rgriff@jhmi.edu.
Roland R
RR
Griffiths
D000284:Administration, Oral; D000328:Adult; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage*; D012054:Reinforcement, Psychology; D012907:Smoking / Q000523:psychology; D011795:Surveys and Questionnaires; D055815:Young Adult
D009538:Nicotine
Drug discrimination; Never-smoker; Nicotine; Oral; Reinforcement; Self-administration; Subjective effects