Abstract
BackgroundAttention deficit hyperactivity disorder (ADHD) is a complex neuropsychiatric disorder with a substantial genetic component. The Spontaneously Hypertensive Rats (SHR), considered as a good animal model of ADHD, also show less anxiety-like behaviors than Lewis (LEW) rats. The use of these inbred rat strains led us to the mapping of two quantitative trait loci (QTL), named Ofil1 (on chromosome 4) and Ofil2 (on chromosome 7), related to locomotion in the central and aversive area of an open field. Herein, we examined whether LEW and SHR rats differ in the acoustic startle reflex, a test used to study the neurobiology of anxiety, and in the prepulse inhibition of the startle response, which is known to be impaired in ADHD patients. The effect of the two aforementioned loci on these behavioral responses was also studied.MethodsFor this latter purpose, rats deriving from an F2 intercross between the LEW and SHR strains were selected according to their genotype at markers flanking the QTLs and bred to obtain lines of rats homozygous LEW/LEW or SHR/SHR for each of the two loci, thus generating 4 genotypic combinations.ResultsThe SHR rats displayed decreased startle and prepulse inhibition levels when compared to LEW rats. Ofil2 affected prepulse inhibition in female rats only.ConclusionThe results suggest that the LEW and SHR strains are appropriate for studying mechanisms of sensorimotor gating and indicate that the locus Ofil2 on rat chromosome 7 contain genes controlling prepulse inhibition, a neuro-behavioral trait of ADHD.
Highlights
Attention deficit hyperactivity disorder (ADHD) is a complex neuropsychiatric disorder that includes behavioral and cognitive features such as inattention and impulsivity/hyperactivity
The objective of the present study was to compare for the first time, LEW and Spontaneously Hypertensive Rats (SHR) rats of both sexes in the acoustic startle test, a paradigm used to study the neurobiology of fear and anxiety [22] and in the prepulse inhibition (PPI) test
The two-way ANCOVA for repeated measures revealed an overall strain effect (F(1,13) = 4.68; p < 0.05) with LEW rats showing increased startle amplitude when compared with SHR rats
Summary
Attention deficit hyperactivity disorder (ADHD) is a complex neuropsychiatric disorder that includes behavioral and cognitive features such as inattention and impulsivity/hyperactivity. Compared to the Lewis (LEW) strain, SHR rats show higher levels of approach towards aversive areas in several behavioral paradigms such as the elevated plus-maze, open-field and black/white box, without differing in general locomotion [8,9,10]. The Spontaneously Hypertensive Rats (SHR), considered as a good animal model of ADHD, show less anxiety-like behaviors than Lewis (LEW) rats The use of these inbred rat strains led us to the mapping of two quantitative trait loci (QTL), named Ofil (on chromosome 4) and Ofil (on chromosome 7), related to locomotion in the central and aversive area of an open field. The effect of the two aforementioned loci on these behavioral responses was studied
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