Sex-specific effects of psychedelics on prepulse inhibition of startle in 129S6SvEv mice.
Prepulse inhibition (PPI) of startle is a sensorimotor gating phenomenon perturbed in a variety of neuropsychiatric conditions. Psychedelics disrupt PPI in rats and humans, but their effects and involvement of the serotonin 5-HT We tested the effect of the psychedelic 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.5 mgkg, i.p.) on startle amplitude and %PPI in response to acoustic stimuli under up to four different experimental conditions that included changes in background and stimulus intensity, prepulse and pulse duration, and interstimulus interval in male and female 129S6SvEv mice. We also evaluated the effect of the 5-HT DOI altered startle amplitude with either pulse alone or prepulse pulse presentations in all PPI conditions, and increased %PPI in three out of four PPI conditions in male mice - an effect that was prevented by M100,907. In female mice, DOI increased %PPI without affecting startle amplitude. %PPI was positively correlated with startle amplitude in males while being negatively correlated in female mice. In male mice, LSD also increased %PPI, although it did not affect startle amplitude, whereas apomorphine and SKF-82,958 induced decreases in %PPI. Our findings highlight a distinct effect of the psychedelic DOI on PPI in 129S6SvEv mice, suggesting 5-HT