title: Acute nicotine induces anxiety and disrupts temporal pattern organization of rat exploratory behavior in hole-board: a potential role for the lateral habenula.
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.
authors.affiliation: Laboratory of Behavioral Physiology, Department of Experimental Biomedicine and Clinical Neurosciences, Human Physiology Section "Giuseppe Pagano", University of Palermo Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Casarrubea
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta ; School of Biosciences, Cardiff University Cardiff, UK.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Davies
authors.affiliation: Laboratory of Behavioral Physiology, Department of Experimental Biomedicine and Clinical Neurosciences, Human Physiology Section "Giuseppe Pagano", University of Palermo Palermo, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Faulisi
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pierucci
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta.
authors.forename: Roberto
authors.initials: R
authors.lastname: Colangeli
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta ; School of Biosciences, Cardiff University Cardiff, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Partridge
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chambers
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cassar
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta.
authors.forename: Mario
authors.initials: M
authors.lastname: Valentino
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta.
authors.forename: Richard
authors.initials: R
authors.lastname: Muscat
authors.affiliation: Laboratory of Behavioral Physiology, Department of Experimental Biomedicine and Clinical Neurosciences, Human Physiology Section "Giuseppe Pagano", University of Palermo Palermo, Italy.
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Benigno
authors.affiliation: Laboratory of Behavioral Physiology, Department of Experimental Biomedicine and Clinical Neurosciences, Human Physiology Section "Giuseppe Pagano", University of Palermo Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Crescimanno
authors.affiliation: Faculty of Medicine and Surgery, Department of Physiology and Biochemistry, University of Malta Msida, Malta ; School of Biosciences, Cardiff University Cardiff, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
keywords: T-pattern analysis; anxiety; dopamine; lateral habenula; nicotine; serotonin