Reversal of dizocilpine-induced disruption of prepulse inhibition of an acoustic startle response by the 5-HT2 receptor antagonist ketanserin.

Prepulse inhibition can be reliably disrupted by non-competitive NMDA receptor antagonists such as dizocilpine. In recent study, we found that the potent D2/5-HT2 receptor antagonist, risperidone, but not the selective dopamine D2 receptor antagonist, raclopride, could reverse this disruption. The present study was therefore designed to examine the effect of the 5-HT2 receptor antagonist, ketanserin, against a dizocilpine-induced disruption of prepulse inhibition, as well as the behavioural stereotypy produced by this drug. Ketanserin (2 mg/kg) reversed the prepulse inhibition disruption produced by dizocilpine (0.15 mg/kg), as did the non-selective 5-HT1/5-HT2 receptor antagonist metergoline (1 mg/kg). Both drugs also attenuated some components of the behavioural stereotypy syndrome produced by dizocilpine (0.15 mg/kg). The present studies therefore suggest an interaction between 5-HT2 receptors and glutamatergic systems. This may be important for the antipsychotic profile of drugs having antagonist activity at 5-HT2 receptors.