Psychology 2010. Vol.1, No.5, 367-369 Copyright © 2010 SciRes. DOI:10.4236/psych.2010.15045 Acquisition of Avoidance Responding in the Fmr1 Knockout Mouse Maria G. Valdovinos 1 , Kelly Ippolito 1 , Lauren Nawrocki 2 , Greg Woods 2 , Craige C. Wrenn 3 1 Department of Psychology, Drake University, Des Moines, USA; 2 Neuroscience Program, Drake University, Des Moines, USA; 3 Department of Pharmaceutical, Biomedical, and Administrative Sciences, Drake University, Des Moines, USA. Email: maria.valdovinos@drake.edu Received August 26 th , 2010; revised November 1 st , 2010; accepted November 19 th , 2010. Fragile X Syndrome (FXS) is the most common inherited cause of mental retardation. Much work has been done characterizing the behavioral phenotype of the animal model of FXS, the Fmr1 knockout mouse. However, very little literature exists on knockout performance in the active avoidance task. This study evaluated if Fmr1 knockouts differed from wild type littermates in avoidance acquisition. Data revealed no difference in acquisi- tion between knockouts and wild types. Keywords: Fragile X Syndrome, Fmr1 Knockout, Active Avoidance In fragile X syndrome (FXS), the most common inherited cause of intellectual disability, a repeat of the trinucleotide sequence CGG (> 200) in the promoter region of the FMR1 gene (located on the X chromosome) leads to a silencing of the gene. FMR1 silencing results in a lack of fragile X mental re- tardation protein (FMRP) production (Brown, 2002) and, in the absence of FMRP, abnormal dendritic development occurs involving an overgrowth of immature spines (Beckel-Mitchener & Greenough, 2004; Irwin, Galvez, & Greenough, 2000). The mechanism by which this occurs is unknown, but is hypothe- sized to be attributed to enhanced mGluR activity (Bear, Huber, & Warren, 2004). Since FXS is an X-linked disorder, it is more common in males than females (Sherman, 2002). Males with FXS present with specific physical and behavioral phenotypes. Physically, males with FXS have long narrow faces, prominent ears, macroorchidism, ophthalmologic problems, and unusual growth patterns (initial rapid growth followed by a decline in adolescence) (Hagerman, 2002). Behaviorally, males with FXS present with hyperarousal and hyperactivity which is some- times manifested in tantrums (Hagerman, 2002). Additionally, individuals with FXS are also commonly diagnosed with aut- ism (Dölen & Bear, 2009). Research has also demonstrated that individuals with FXS engage in a high degree of avoidance behavior. One proposed explanation of this behavior has been the high degree of social anxiety experienced by those with FXS which appears to mani- fests itself in the form of social avoidance (e.g., withdrawal, eye-gaze avoidance, self-injurious behavior (SIB), and aggres- sion) (Kau, Reider, Payne, Meyer, & Freund, 2000). Indeed, in a survey of psychotropic medication use among those diag- nosed with FXS, Valdovinos and colleagues (2009) found that approximately 36% of their sample were reported to engage in aggressive behavior, 42% in refusals or opposition, 43% in SIB, and 25% in withdrawal. These findings are significant as re- search has demonstrated that in a majority of cases problem behaviors such as aggression and SIB are maintained by nega- tive reinforcement or escape from some noxious stimulus (e.g., demands, social interactions) (Iwata et al., 1994). Case in point, in a survey of families with boys diagnosed with FXS, Symons and colleagues (2003) found that a majority of their sample was reported to engage or have engaged in self-injurious behavior and that SIB was more likely to have occurred after the presen- tation of a difficult demand suggesting an escape function. Another possible explanation for avoidance behavior in those diagnosed with FXS is that perhaps those with FXS experience hyperarousal of the sympathetic nervous system in response to stimuli (auditory, visual, and tactile) (Hagerman, 2002) as evi- dence by increased cortisol reactivity (Hessl, Glaser, Dyer- Friedman, & Reiss, 2006) and increased magnitude of electro- dermal activity (Miller et al., 1999). The Fmr1 knockout mouse has been demonstrated to be an appropriate model for the human condition as similarities have been observed in both physical and behavioral characteristics (The Dutch Belgium Consortium, 1994). In assessments of avoidance behavior in the knockout, data published have been on the knockout’s performance on the passive avoidance test, an assessment of learning and memory. Results of have not revealed any differences between wild type and knockout per- formance (The Dutch Belgium Consortium, 1994; Qin, Kang, & Smith, 2005). However, limited data on the performance of the Fmr1 knockout on the active avoidance test exist. The dif- ference between these two tasks is that in one test, the ability to associate one side of a cage (i.e., the dark side as opposed to bright side) with shock is measured whereas with the other test, the ability to associate a cue with the shock and subsequent avoidance of the shock is measured. Thus, with the human condition in mind, we assessed nega- tively reinforced behavior in Fmr1 knockout (KO) and wild type (WT) littermates using an active avoidance test. Given the research on avoidance behavior in individuals with FXS, we