Neural sensorimotor gating mechanisms prevent the interruption of ongoing information
processing routines by ensuing stimuli to permit mental integration and adaptive behavior.
Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is now being
investigated using murine models to exploit transgenic and "knockout" technology.
The present studies were undertaken to evaluate potential murine strain differences
in the effects of serotonergic drugs on PPI and habituation. Two strains used most
often as a genetic background for transgenic or knockout manipulations, C57BL/6 and
129Sv, and the outbred ICR strain were used. We assessed the effects of the 5-HT(1A/1B)
agonist 5-methoxy-3(1,2,3,6)tetrahydropyridin-4-yl-1H-indole (RU24969), the 5-HT(1A)
agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT(2A/2C) agonist
(+/-)2,5-dimethoxy-4-methylamphetamine (DOM), and the serotonin releaser (+)3, 4-methylenedioxy-N-methylamphetamine
(MDMA) on PPI and habituation of acoustic startle in the three strains. C57BL/6 mice
exhibited lower baseline PPI levels than 129Sv and ICR mice, and 129Sv mice habituated
less than C57BL/6 and ICR mice. MDMA decreased PPI in C57BL/6 and ICR, but not 129Sv
mice, and RU24969 disrupted habituation in C57BL/6 and 129Sv, but not ICR mice. Lastly,
RU24969 decreased and 8-OH-DPAT increased PPI across all strains, although qualitative
differences were observed. Thus, both baseline and serotonergic drug-induced effects
on murine PPI and habituation are strain-dependent.