Amphetamine metabolite p-hydroxyamphetamine (p-OHA) has been shown to have many pharmacological effects, including causing psychostimulant-induced behaviors such as hyperlocomotion and head-twitch response. We have previously reported that p-OHA induces prepulse inhibition (PPI) disruptions in mice, and the PPI disruptions are involved in the dopaminergic system. In this study, we investigated the involvement of the serotonin (5-HT) and noradrenaline (NA) neurotransmission in p-OHA-induced PPI disruptions in mice. As a result, p-OHA-induced PPI disruptions were attenuated by pretreatment with ketanserin (a 5-HT2A/2C receptor antagonist), MDL100,907 (a selective 5-HT2A receptor antagonist), 5,7-dihydroxytryptamine (a 5-HT neurotoxin), p-chlorophenylalanine (a 5-HT synthesis inhibitor) and prazosin (a selective α1 receptor antagonist), but were not attenuated by pretreatment with DSP-4 (a NA neurotoxin), fuzaric acid (a NA synthesis inhibitor). These results suggest that the 5-HT neurotransmission is strongly involved in p-OHA-induced PPI disruptions, with ancillary involved of α1 receptors.
