title: Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats.
abstract: A wider diversity of drug treatments to aid smoking cessation is needed to help tailor the most efficacious treatment for different types of smokers. This study was conducted to determine whether amitifadine, which inhibits re-uptake of dopamine, norepinephrine and serotonin, would decrease nicotine self-administration at doses that do not cause adverse side effects. Adult female Sprague-Dawley rats were trained to self-administer nicotine intravenous (IV) and were given acute doses of amitifadine in a repeated measures counterbalanced design. Effects of amitifadine on locomotor activity and food motivated responding were also evaluated. Chronic amitifadine effects were also examined. The 30 mg/kg amitifadine dose significantly reduced nicotine self-administration. The 5 and 10 mg/kg doses reduced nicotine self-administration during the first 15 min of the session when the greatest amount of nicotine was self-administered. The 30 mg/kg amitifadine dose, but not the lower doses caused a significant reduction in locomotor activity averaged over the one-hour session and reduced food motivated responding. The 10 mg/kg dose caused hypoactivity at the beginning of the session, but 5 mg/kg did not cause any hypoactivity. The effects of chronic amitifadine treatment (10 mg/kg) over the course of 15 sessions was also determined. Amitifadine caused a significant reduction in nicotine self-administration, which was not seen to diminish over two consecutive weeks of treatment and a week after enforced abstinence. Amitifadine significantly reduced nicotine self-administration. This prompts further research to determine if amitifadine might be an effective treatment for smoking cessation.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: edlevin@duke.educ.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Wells
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Rezvani
authors.affiliation: Euthymics Bioscience Inc., USA.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Bymaster
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jed E
authors.initials: JE
authors.lastname: Rose
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D005260:Female; D005502:Food; D009042:Motivation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D016540:Smoking Cessation; D013997:Time Factors
chemical_list: C474071:1-(3,4-dichlorophenyl)-3-azabicyclo-(3.1.0)hexane hydrochloride; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014179:Neurotransmitter Uptake Inhibitors; D009538:Nicotine
keywords: Amitifadine; Dopamine; Nicotine; Norepinephrine; Self-administration; Serotonin; Treatment