title: Repeated nicotine exposure in adolescent rats: Reduction of medial habenular activity and augmentation of nicotine preference.
abstract: 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.
authors.affiliation: Department of Science Education, Dankook University, 152 Jukjeon-ro, Suji-gu, Yongin-si, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: Hyunchan
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Brain and Cognitive Sciences, Brain Disease Research Institute, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Mi-Seon
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Department of Brain and Cognitive Sciences, Brain Disease Research Institute, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Chung
authors.affiliation: Department of Science Education, Dankook University, 152 Jukjeon-ro, Suji-gu, Yongin-si, Gyeonggi-do 448-701, Republic of Korea. Electronic address: jihyun2@dankook.ac.kr.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Noh
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects; D019262:Habenula / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D055697:Taste Perception / Q000187:drug effects; D046509:Tissue Culture Techniques
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine
keywords: Addiction; Aversion; Extracellular recording; Interpeduncular nucleus; Medial habenula; Nicotine consumption