FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability

Abstract

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are mutations causing the loss of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) leading to Fragile X syndrome (FXS), a common form of inherited intellectual disability and the leading monogenic cause of ASD. Being a pivotal regulator of motor activity, motivation, attention, and reward processing, dopaminergic neurotransmission has a key role in several neuropsychiatric disorders, including ASD. Fmr1Δexon 8 rats have been validated as a genetic model of ASD based on FMR1 deletion, and they are also a rat model of FXS. Here, we performed behavioral, biochemical and in vivo SPECT neuroimaging experiments to investigate whether Fmr1Δexon 8 rats display ASD-like repetitive behaviors associated with changes in striatal dopamine transporter (DAT) availability assessed through in vivo SPECT neuroimaging. At the behavioral level, Fmr1Δexon 8 rats displayed hyperactivity in the open field test in the absence of repetitive behaviors in the hole board test. However, these behavioral alterations were not associated with changes in striatal DAT availability as assessed by non-invasive in vivo SPECT and Western blot analyses.

Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function

“…Noteworthy, both WT and KO rats demonstrated reduced levels of motor activity due to the longer exposure and subsequent familiarity with the open-field apparatus. In agreement with our results, increased motor activity as deduced by the total time spent in the open-field apparatus was observed for Fmr1 KO compared to WT rats [ 38 , 39 ]. Another study [ 40 ] reported that KO rats were hyperactive, only during the first recording interval.…”

Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function

“…Noteworthy, both genotypes demonstrated reduced levels of motor activity due to the longer exposure and subsequent familiarity to the open eld apparatus. In agreement with our results, increased motor activity as deduced by the total time spent in the open eld apparatus was observed for Fmr1 KO compared to WT rats [ 35,36 ].In another study [ 37 ],reported that KO rats were hyperactive, only during the rst recording interval. On the other hand, previous studies have shown either no change [ [38][39][40] or a reduction in spontaneous motor activity compared to the WT counterparts [ 8,41 ].…”

Outcomes of early social experiences on glucocorticoid and endocannabinoid systems in the prefrontal cortex of male and female adolescent rats

“…The elevated plus maze (EPM) apparatus comprised two open (50 × 10 × 40 cm; l × w × h) and two closed arms (50 × 10 × 40 cm; l × w × h) that extended from a common central platform (10 × 10 cm). The test was performed as previously reported ( Manduca et al, 2015 ; D’Elia et al, 2022 ). At PND 35, rats were individually placed on the central platform of the maze for 5 min.…”