SEROTONIN(1B) RECEPTOR MODULATION OF STARTLE REACTIVITY, HABITUATION,AND PREPULSE INHIBITION IN WILD-TYPE AND SEROTONIN(1B) KNOCKOUT MICE

Two operational measures of central information processing mechanisms are habituation and prepulse inhibition (PPI) of the startle response. Both measures can be assessed reliably in humans and other animals, a nd have been shown to be deficient in patients with schizophrenia. The three present experiments assessed the involvement of the serotonin(1 B) (5-HT1B) receptor in modulating startle reactivity, habituation, an d PPI by comparing 5-HT1B receptor gene knockout (5-HT1B knockout) wit h wild-type 129/Sv mice. In experiment 1, female mice received saline, 2.0 mg/kg methoxy-3(1,2,3,6)tetrahydropyridin-4-yl-1H-indole (RU24969 ), a 5-HT1A/1B agonist, and 1.0 mg/kg 8-hydroxy-2(di-n-propylamino)tet ralin (8-OH-DPAT), a selective 5-HT1A agonist. Female mice received sa line, 10.0 mg/kg RU24969, and 5.0 mg/kg 8-OH-DPAT in experiment 2, and male mice received saline, 10.0 mg/kg RU24969, and 5.0 mg/kg 8-OH-DPA T in experiment 3. All three studies used identical within-subjects de signs. Two phenotypic differences were observed following saline treat ment: 5-HT1B knockout mice consistently exhibited a small increase in PPI that achieved significance in experiment 1; and 5-HT1B knockout ma le mice exhibited robust decreases in startle reactivity. Habituation was disrupted consistently by RU24969 in wild-type but not in 5-HT1B k nockout mice, while 8-OH-DPAT had no effect on habituation. Consistent with the phenotypic difference in PPI, the high dose of RU24969 signi ficantly and consistently reduced PPI in wild-type but not in 5-HT1B k nockout mice. 8-OH-DPAT increased PPI in both wild-type and 5-HT1B kno ckout mice in every experiment. These findings suggest that 5-HT1B rec eptors modulate startle reactivity, habituation, and PPI in mice. Addi tionally, a potential species difference may exist in the behavioral e ffects of 5-HT1A receptor activation on PPI.