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.

Sex differences in response to nicotine in C57Bl/6:129SvEv mice

“…Studies examining nicotine-conditioned place preference in mice have been performed almost exclusively in males ( Agatsuma et al, 2006 ;Balerio, Aso, & Maldonado, 2005 ;Grabus, Martin, Brown, & Damaj, 2006 ;McGeehan & Olive, 2003 ;Nolley & Kelley, 2007 ;Rauhut, Hawrylak, & Mardekian, 2008 ;Sahraei et al, 2004 ) or in both males and females Walters, Brown, Changeux, Martin, & Damaj, 2006 ;Walters, Cleck, Kuo, & Blendy, 2005 ). Males and females of the ICR mouse strain have been characterized extensively but in separate studies ( Grabus et al, 2006 ;Kota, Martin, & Damaj, 2008 ;Kota, Martin, Robinson, & Damaj, 2007 ).…”

“…To examine sex differences in voluntary oral nicotine consumption, males and females were evaluated in the two-bottle choice paradigm across a range of nicotine concentrations for which reward or aversion has been reported ( Agatsuma et al, 2006 ;Lee et al, 2004 ;Zhu et al, 2005 ). Nicotine preference ratios revealed a reduced preference for nicotine (aversion) in males as nicotine concentration increased, whereas females consumed nicotine and water equally regardless of the nicotine concentration ( Figure 1 ).…”

“…This procedure measures directly the amount of nicotine consumed and enables investigators to distinguish direct nicotine effects from nicotineassociated cues, a prominent feature of the place-conditioning paradigm. Two-bottle choice has been reported to demonstrate both aversion and preference for nicotine in mice depending on nicotine concentration ( Adriani, Macri, Pacifi ci, & Laviola, 2002 ;Agatsuma et al, 2006 ;Klein, Stine, Pfaff, & Vandenbergh, 2003 ;Klein, Stine, Vandenbergh, Whetzel, & Kamens, 2004 ;Lee, Chen, Shih, & Hiroi, 2004 ;Meliska, Bartke, McGlacken, & Jensen, 1995 ;Robinson, Marks, & Collins, 1996 ;Zhu et al, 2005 ). In a twobottle choice paradigm, mice are exposed to two bottles: one containing water and the other nicotine, the locations of which are switched every few days to prevent conditioned place associations from masking drug effects ( Klein, 2001 ;Klein et al, 2004 ;Shaham, Alvares, Nespor, & Grunberg, 1992 ;Todte et al, 2001 ).…”

The Absence of Blocking Innicotine High-Responders as a Possible Factor in the Development of Nicotine Dependence?

“…Indeed, part of the motivation for this study was a resolution of the paradoxical finding that nicotine alone displays very little in the way of 1 st phase reinforcement effect and yet is one of the most commonly abused substances in the world. While a portion of this paradox may be explained by the enhancement of nicotine's 1st phasereinforcement value with the addition of monoamineoxidase-inhibitors and other chemicals commonly found in cigarette smoke [41][42][43][44][45][46] it seems likely that such effects require previous experience with nicotine [47,48]. However, when our analysis focused on nicotine, and food, highresponders, Redish's (2004) hypothesis was robustly supported with significant learning shown for a 2 nd phase CS among blocked nicotine-rewarded animals but not foodrewarded animals and no evidence of blocking using repeated-measures analysis.…”

Quantitative Trait Locus Analysis Identifies Rat Genomic Regions Related to Amphetamine-Induced Locomotion and Gαi3 Levels in Nucleus Accumbens

“…AIL differs from other types of locomotion, such as noveltyinduced locomotion (NIL), which has been associated with stress responses. A complex relationship exists between drug-induced behaviors and novelty responses in rodents (Hiroi and Agatsuma, 2005;Agatsuma et al, 2006). AIL is differentially regulated in rats with high or low levels of spontaneous exploratory behavior (Corda et al, 2005;Alttoa et al, 2007).…”