Repeated nicotine exposure in adolescent rats: Reduction of medial habenular activity and augmentation of nicotine preference

Hyunchan Lee, Mi Seon Kang, Jun mo Chung, Jihyun Noh

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Adolescence is a critical period for the initiation of tobacco use. Nicotine not only stimulates brain reward circuits to establish and maintain the tobacco smoking habit, but also produces aversive reactions to nicotine after initial exposure, due to its noxious properties. Although new insights into the mechanisms that regulate nicotine avoidance could result in an advantageous treatment strategy for addiction, little is known about the mechanism of nicotine aversion in adolescence. Because growing evidences suggest that the habenula to interpeduncular nucleus circuitry plays a critical role in nicotine aversion, we investigated the effects of repeated nicotine exposure on the electrical activity of medial habenular neurons in adolescent rats, using extracellular recordings. Nicotine strongly increased the frequency of spontaneous spike activity in the medial habenula of naïve rats. In repeated nicotine-injected rats, we found a reduction in nicotine-induced spontaneous spike frequency, such that these neurons displayed a significantly lower basal activity and reduced spontaneous activity upon re-exposure to nicotine. Moreover, nicotine intake preference in repeated nicotine-injected rats is significantly more increased than that in saline-injected rats. These results demonstrate that repeated phases of nicotine exposure induce a functional switch in the activity of medial habenular neurons in adolescent rats and suggest that medial habenular activity is one of mediators for an inhibitory motivational signal that limits nicotine consumption.

Original languageEnglish
Pages (from-to)345-350
Number of pages6
JournalPhysiology and Behavior
StatePublished - 1 Jan 2015

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2011-0013573 ) to JN and in part by the GT5 grant funded by Ewha W. University ( EWHA-GT5 ) to JMC.

Publisher Copyright:
© 2014 Elsevier Inc.


  • Addiction
  • Aversion
  • Extracellular recording
  • Interpeduncular nucleus
  • Medial habenula
  • Nicotine consumption


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