Prepulse inhibition (PPI) is a measure of sensorimotor gating that is deficient in schizophrenia. In rats, administration of the serotonin-1A (5-HT1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), causes a disruption of PPI. It is unclear whether this effect is due to the activation of pre- or post-synaptic 5-HT1A receptors, however pre-synaptic receptors located in the dorsal raphe nucleus (DRN) may play a role. Our previous research showed that castrated rats have a reduced sensitivity to 8-OH-DPAT-induced disruptions of PPI. Therefore, in , male Sprague-Dawley rats were sham-operated or castrated and micro-injected with 8-OH-DPAT directly into the DRN. In , male rats were sham-operated or received a selective serotonergic, 5,7-dihydroxytryptamine lesion of the DRN. 8-OH-DPAT was injected subcutaneously in these rats. In both sham-operated and castrated rats, a micro-injection of 8-OH-DPAT into the DRN did not disrupt PPI. Instead, in castrated rats, 8-OH-DPAT treatment tended to increase PPI. A DRN lesion caused a significant reduction in 5-HT content in the frontal cortex (70% reduction), striatum (69%) and ventral hippocampus (76%). In both sham-operated and DRN-lesioned rats, systemic 8-OH-DPAT significantly disrupted PPI. Taken together, these data suggest that the disruption of PPI observed in rats with systemic 8-OH-DPAT treatment is predominantly due to an activation of post-synaptic, rather than pre-synaptic, 5-HT1A receptors.