Functional behavioral homology between rat 5-HT1B and guinea pig 5-HT1D receptors in the modulation of prepulse inhibition of startle.

Abstract

The serotonin (5-HT) 1B receptor in rats and mice appears to be homologous to the 5-HT1D receptor found in other mammals, such as guinea pigs and humans. The present series of experiments explored the functional similarity between the rat 5-HT1B receptor and the guinea pig 5-HT1D receptor on two behavioral measures known to be influenced by 5-HT1B receptor manipulations in rats: prepulse inhibition of the startle response (PPI) and locomotor activity. Because the 5-HT1B agonist RU 24969 disrupts PPI and stimulates locomotor behavior in rats, it was predicted that the 5-HT1D agonist, SDZ 219-964, would demonstrate a similar behavioral profile in guinea pigs. In support of this hypothesis, SDZ 219-964 was found to disrupt PPI dose-dependently (1.0 and 2.0 mg/kg) without significantly affecting startle amplitude and to increase locomotor activity (0.5-2.0 mg/kg) in guinea pigs. In guinea pigs, RU 24969 failed to affect PPI, although it did increase locomotor activity, indicating that RU 24969 may have activity at the 5-HT1D receptor. As expected, RU 24969 in rats disrupted PPI (2.5 and 5.0 mg/kg) and significantly increased locomotor activity (1.25-5.0 mg/kg). In rats, however, SDZ 219-964 had generalized, stimulatory effects on startle reactivity, without independent effects on PPI or locomotor activity. The spatial patterns of locomotion exhibited by guinea pigs treated with SDZ 219-964 versus those of rats treated with RU 24969 demonstrate important qualitative differences in structure, indicating that the neural substrates subserving these effects may be different. It is concluded that a functional similarity exists between 5-HT1D and 5-HT1B receptors with regard to the modulation of sensorimotor inhibition and, to a lesser extent, locomotor activity.