Multiple serotonin receptor subtypes modulate prepulse inhibition of the startle response in rats

The phenomenon of prepulse inhibition (PPI) of the acoustic startle reflex is widely used as an operational measure of sensorimotor gating mechanisms. Because sensorimotor gating abnormalities have been identified in schizophrenic patients, the exploration of the neural substrates involved in PPI may provide insight into the neural dysfunctions underlying this disorder. Both dopaminergic and glutamatergic systems are involved in the modulation of PPI in rats. In addition, the present studies demonstrate complex serotonergic influences in this phenomenon. Specifically, both the 5-HT2 agonist, DOI, (2,5-dimethoxy-4-iodoamphetamine), and the 5-HT1B agonist, RU 24969, [5-methoxy-3(1,2,3,6)tetrahydropyridin-4- yl]-1H-indole, potently and reversibly disrupted PPI. The 5-HT2C agonist mCPP, [1-(m)-chlorophenyl-piperazine], was ineffective. Furthermore, ketanserin (2.0 mg/kg) and haloperidol (0.1 mg/kg) but not (+/-)propranolol (20.0 mg/kg) blocked the effect of DOI. In addition, the same doses of haloperidol, and, to a lesser extent, (+/-)propranolol, prevented the disruption of PPI induced by RU 24969. Together with previous reports of 5-HT1A involvement in PPI, these results argue for multiple serotonergic mechanisms in the modulation of PPI.