Abstract
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-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. The 5-HT1A/1B agonist RU24969 reduced PPI and habituation in WT and 1AKO, but not 1BKO mice, whereas the 5-HT1A agonist 8-OH-DPAT increased PPI in WT and 1BKO, but not in 1AKO mice. Similarly, the selective 5-HT1B agonist anpirtoline reduced PPI in WT, but not in 1BKO mice. In experiments using intact 129Sv mice, the 5-HT1A agonist flesinoxan increased PPI while anpirtoline decreased PPI and habituation. Findings suggest that 5-HT1B receptor activation decreases PPI and habituation, and 5-HT1A receptor activation increases PPI in mice.
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Acknowledgements
The authors acknowledge the generous gifts of flesinoxan from Solvay Pharma, and RU24969 from Roussel UCLAF. This work was supported by grants from the National Institute on Drug Abuse (R02DA02925 & R01DA09862–01), the National Institute of Mental Health (NIMH) P01MH48126–06, the National Alliance for Research on Schizophrenia and Depression (NARSAD), and the U.S. Veterans Affairs VISN22 Mental Illness Research, Education, and Clinical Center. S.C. Dulawa was supported by a predoctoral NRSA from NIMH (F31-MH12249–01). C. Gross was supported by a grant from NIMH (F32MH12364–01). M.A. Geyer holds equity interest in San Diego Instruments, Inc.
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Dulawa, S., Gross, C., Stark, K. et al. Knockout Mice Reveal Opposite Roles for Serotonin 1A and 1B Receptors in Prepulse Inhibition. Neuropsychopharmacol 22, 650–659 (2000). https://doi.org/10.1016/S0893-133X(99)00164-5
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DOI: https://doi.org/10.1016/S0893-133X(99)00164-5
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