Knockout mice reveal opposite roles for serotonin 1A and 1B receptors in prepulse inhibition

The serotonergic system is involved in the modulation of prepulse inhibitio n (PPI) and habituation of startle, which are deficient in schizophrenia pa tients. PPI is the reduction in startle amplitude that occurs when a weak " prepulse" precedes a startling stimulus by 30-500 msec. The roles of 5-HT1A and 5-HT1B receptors in modulating PPI and habituation were examined using wild-type (WT), 5-HT1A knockout (1AKO), and 5-HT1B knockout (1BKO) mice. T he 5-HT1A/1B agonist RU24969 reduced PPI and habituation in WT and 1AKO, bu t not 1BKO mice, whereas the 5-HT1A agonist 8-OH-DPAT increased PPI in WT a nd 1BKO, but not in 1AKO mice. Similarly, the selective 5-HT1B agonist anpi rtoline reduced PPI in WT, but not in 1BKO mice. In experiments using intac t 129Sv mice, the 5-HT1A agonist flesinoxan increased PPI while anpirtoline decreased PPI and habituation. Findings suggest that 5-HT1B receptor activ ation decreases PPI and habituation, and 5-HT1A receptor activation increas es PPI in mice.