title: Monoamine oxidase A knockout mice exhibit impaired nicotine preference but normal responses to novel stimuli.
abstract: Nicotine is thought to act on brain monoamine systems that normally mediate diverse motivational behaviors. How monoamine-related genes contribute to behavioral traits (e.g. responses to novel stimuli) comorbid with the susceptibility to nicotine addiction is still poorly understood. We examined the impact of constitutive monoamine oxidase A (MAOA) deficiency in mice on nicotine reward and responses to novel stimuli. Age-matched, male Maoa-knockout (KO) mice and wild-type (WT) littermates were tested for nicotine-induced conditioned place preference (CPP); voluntary oral nicotine preference/intake; spontaneous locomotor activity in a novel, inescapable open field; and novelty place preference. Nicotine preference in WT mice was reduced in Maoa-KO mice in the CPP and oral preference/intake tests. Control experiments showed that these phenotypes were not due to abnormalities in nicotine metabolism, fluid intake or response to taste. In contrast, Maoa-KO mice were normal in their behavioral response to a novel, inescapable open field and in their preference for a novel place. The observed phenotypes suggest that a constitutive deficiency of MAOA reduces the rewarding effects of nicotine without altering behavioral responses to novel stimuli in mice. Constitutive MAOA activity levels are likely to contribute to the vulnerability or resiliency to nicotine addiction by altering the rewarding effects of nicotine.
authors.affiliation: Laboratory of Molecular Psychobiology, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Soh
authors.initials: S
authors.lastname: Agatsuma
authors.forename: Moonsook
authors.initials: M
authors.lastname: Lee
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhu
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.forename: Jean C
authors.initials: JC
authors.lastname: Shih
authors.forename: Isabelle
authors.initials: I
authors.lastname: Seif
authors.forename: Noboru
authors.initials: N
authors.lastname: Hiroi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal; D003213:Conditioning, Psychological; D005106:Exploratory Behavior; D006185:Habituation, Psychophysiologic; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000172:deficiency* / Q000235:genetics; D009043:Motor Activity; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011803:Quinine / Q000008:administration & dosage; D012201:Reward; D012439:Saccharin / Q000008:administration & dosage; D012646:Self Administration
chemical_list: D009538:Nicotine; D011803:Quinine; D008995:Monoamine Oxidase; D012439:Saccharin