Alpha-asarone attenuates depression-like behavior in nicotine-withdrawn mice: Evidence for the modulation of hippocampal pCREB levels during nicotine-withdrawal

Eur J Pharmacol. 2018 Jan 5:818:10-16. doi: 10.1016/j.ejphar.2017.10.025. Epub 2017 Oct 16.

Abstract

In the present study, the effect α-asarone on nicotine withdrawal-induced depression-like behavior in mice was investigated. In this study, mice were exposed to drinking water or nicotine solution (10-200µg/ml) as a source of drinking for forty days. During this period, daily fluid consumption, food intake and body weight were recorded. The serum cotinine level was estimated before nicotine withdrawal. Naïve mice or nicotine-withdrawn mice were treated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) for eight consecutive days and the forced swim test (FST) or locomotor activity test was conducted. In addition, the effect of α-asarone or bupropion on the hippocampal pCREB, CREB and BDNF levels during nicotine-withdrawal were measured. Results indicated that α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment did not significantly alter the immobility time in the FST or spontaneous locomotor activity in naïve mice. However, the immobility time of nicotine-withdrawn mice was significantly attenuated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment in the FST. Besides, α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment significantly attenuated the hippocampal pCREB levels in nicotine-withdrawn mice. Overall, the present results indicate that α-asarone treatment attenuated the depression-like behavior through the modulation of hippocampal pCREB levels during nicotine-withdrawal in mice.

Keywords: (-)-nicotine hydrogen tartrate (PubChem CID: 24867513); Alpha-asarone (PubChem CID: 636822); Bupropion hydrochloride (PubChem CID: 62844); Depression; Mouse; Nicotine; Tween 80 (PubChem CID: 443315); Withdrawal; α-asarone, bupropion.

MeSH terms

  • Allylbenzene Derivatives
  • Animals
  • Anisoles / pharmacology*
  • Anisoles / therapeutic use
  • Behavior, Animal / drug effects*
  • Body Weight / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Depression / drug therapy*
  • Depression / metabolism
  • Depression / physiopathology
  • Drinking / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Locomotion / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nicotine / pharmacology*
  • Phosphoproteins / metabolism
  • Substance Withdrawal Syndrome / psychology*

Substances

  • Allylbenzene Derivatives
  • Anisoles
  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Phosphoproteins
  • asarone
  • Nicotine