Abstract
Nicotine is one of the most addictive drugs of abuse. Tobacco smoking is a major cause of many health problems, and is the first preventable cause of death worldwide. Several findings show that nicotine exerts significant aversive as well as the well-known rewarding motivational effects. Less certain is the anatomical substrate that mediates or enables nicotine aversion. Here, we show that acute nicotine induces anxiogenic-like effects in rats at the doses investigated (0.1, 0.5, and 1.0 mg/kg, i.p.), as measured by the hole-board apparatus and manifested in behaviors such as decreased rearing and head-dipping and increased grooming. No changes in locomotor behavior were observed at any of the nicotine doses given. T-pattern analysis of the behavioral outcomes revealed a drastic reduction and disruption of complex behavioral patterns induced by all three nicotine doses, with the maximum effect for 1 mg/kg. Lesion of the lateral habenula (LHb) induced hyperlocomotion and, strikingly, reversed the nicotine-induced anxiety obtained at 1 mg/kg to an anxiolytic-like effect, as shown by T-pattern analysis. We suggest that the LHb is critically involved in emotional behavior states and in nicotine-induced anxiety, most likely through modulation of monoaminergic nuclei.
Highlights
Tobacco smoking is a serious health problem worldwide and is well known to be one of the major causes of death in developed countries (Vella and Di Giovanni, 2013)
The first aim of the current study was to resolve the seemingly conflicting observations in the literature regarding the link between nicotine and anxiety, by directly comparing the effects of different doses of nicotine on anxiety-like animal behavior using hole-board apparatus and quantitative and qualitative analysis
We demonstrated that acute administration of medium-high doses of nicotine (0.1–1 mg/kg, i.p.) induced clear anxiogeniclike effects in normal rats
Summary
Tobacco smoking is a serious health problem worldwide and is well known to be one of the major causes of death in developed countries (Vella and Di Giovanni, 2013). Initial aversion to nicotine experienced by first-time smokers, including anxiety, is a common experience (Newhouse et al, 1990) which subsequently can be a very important factor since it can decrease the likelihood of developing a tobacco addiction (Sartor et al, 2010). The rewarding and aversive nicotine effects are likely mediated by a heterogeneous population of nAChR subtypes in different neuronal circuits. The aversive nicotine effects, including anxiety, might be mediated by the lateral habenula (LHb; Fowler and Kenny, 2014), a small epithalamic structure that has been shown to convey negative motivational signals (Bianco and Wilson, 2009)
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