Serotonin1B receptor modulation of startle reactivity, habituation, and prepulse inhibition in wild-type and serotonin1B knockout mice

Abstract

 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, and have been shown to be deficient in patients with schizophrenia. The three present experiments assessed the involvement of the serotonin_1B (5-HT_1B) receptor in modulating startle reactivity, habituation, and PPI by comparing 5-HT_1B receptor gene knockout (5-HT_1B knockout) with wild-type 129/Sv mice. In experiment 1, female mice received saline, 2.0 mg/kg 5-methoxy-3(1,2,3,6)tetrahydropyridin-4-yl-1H-indole (RU24969), a 5-HT_1A/1B agonist, and 1.0 mg/kg 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT_1A agonist. Female mice received saline, 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-DPAT in experiment 3. All three studies used identical within-subjects designs. Two phenotypic differences were observed following saline treatment: 5-HT_1B knockout mice consistently exhibited a small increase in PPI that achieved significance in experiment 1; and 5-HT_1B knockout male mice exhibited robust decreases in startle reactivity. Habituation was disrupted consistently by RU24969 in wild-type but not in 5-HT_1B knockout mice, while 8-OH-DPAT had no effect on habituation. Consistent with the phenotypic difference in PPI, the high dose of RU24969 significantly and consistently reduced PPI in wild-type but not in 5-HT_1B knockout mice. 8-OH-DPAT increased PPI in both wild-type and 5-HT_1B knockout mice in every experiment. These findings suggest that 5-HT_1B receptors modulate startle reactivity, habituation, and PPI in mice. Additionally, a potential species difference may exist in the behavioral effects of 5-HT_1A receptor activation on PPI.