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

The serotonergic system is involved in the modulation of prepulse inhibition (PPI) and habituation of startle, which are deficient in schizophrenia patients. 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-HT(1A) and 5-HT(1B) receptors in modulating PPI and habituation were examined using wild-type (WT), 5-HT(1A) knockout (1AKO), and 5-HT(1B) knockout (1BKO) mice. The 5-HT(1A/1B) agonist RU24969 reduced PPI and habituation in WT and 1AKO, but not 1BKO mice, whereas the 5-HT(1A) agonist 8-OH-DPAT increased PPI in WT and 1BKO, but not in 1AKO mice. Similarly, the selective 5-HT(1B) agonist anpirtoline reduced PPI in WT, but not in 1BKO mice. In experiments using intact 129Sv mice, the 5-HT(1A) agonist flesinoxan increased PPI while anpirtoline decreased PPI and habituation. Findings suggest that 5-HT(1B) receptor activation decreases PPI and habituation, and 5-HT(1A) receptor activation increases PPI in mice.