Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice

Eur J Pharmacol. 2015 May 5;754:190-8. doi: 10.1016/j.ejphar.2015.02.033. Epub 2015 Mar 3.


Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal.

Keywords: Agmatine; Anxiety; Depression; Nicotine withdrawal; Somatic behavior.

MeSH terms

  • Agmatine / administration & dosage
  • Agmatine / pharmacokinetics
  • Agmatine / pharmacology
  • Agmatine / therapeutic use*
  • Animals
  • Anxiety / chemically induced
  • Anxiety / drug therapy*
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Depression / chemically induced
  • Depression / drug therapy*
  • Infusions, Intraventricular
  • Male
  • Mice
  • Nicotine / adverse effects*
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / prevention & control
  • Tobacco Use Disorder / drug therapy


  • Nicotine
  • Agmatine