A QTL on rat chromosome 7 modulates prepulse inhibition, a neuro-behavioral trait of ADHD, in a Lewis x SHR intercross.

BACKGROUND

Attention 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.

METHODS

For 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.

RESULTS

The SHR rats displayed decreased startle and prepulse inhibition levels when compared to LEW rats. Ofil2 affected prepulse inhibition in female rats only.

CONCLUSION

The 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.