403. Oxytocin produces novel antipsychotic-like effects on prepulse inhibition

Abstract

Oxytocinacts as a neurotransmitterin the central nervoussystemand playsan importantrole in the regulationof a numberof processeswhich are dismptedin schizophreniaincludingmemoryand social bonding. Schizophreniapatients have been found to have altered oxytoeinergic functionrelative to normalcontrols.This studyexaminedthe possible role of oxytocin in schizophrenia-relevant brain processes using an animal model of an informationprocessing deficit associated with schizophrenia.Prepulse inhibition (PPI), an operationalmeasure of sensorimotorgating,is the normrdsuppressionof the startfereflexwhen the intensestartlingstimulus(“pulse”)is precededby weakprestimulus (“repulse”). PPIis decreasedin schizophreniapatientsandis thoughtto represent a deficit in their ability to filter irrelevant environmental stimuli.PPI can be reducedin rats treatedwithpsychornimeticsuchas the dopamineagonistsamphetamineand apomorphineor the NMDA antagonistsPCP and dizocilpine(MK801).Antipsychoticscan restore psychomimetic-reduced PPI. In this study,subcntaneoudyadministered oxytoeinhad no effect on baseline PPI or on the underlyingstartle responseamplitude.Oxytoeindose-deperrdentJy restoredPPI decreased by dizocilpineand amphetaminebut not by apomorpfrirre. Theseresults suggest that oxytocincan modulatedoparninergicand glutamatergic regulationof PPI. Oxytocineffeetssuggestan antipsychotic-likeprofile that is highly novel and not characteristicof known arrtipsychotics belongingto eitherthe “typicaf”or “atypical”antipsychoticfamiliesand which does not appear to involve doparninereceptor antagonism. Oxytocin,therefore,mayact asanendogenousantipsychoticandchanges in the endogenousoxytocinsystemmay play a role in the pathophysiologyof schizophreniaor the therapeuticactionof arrtipsychotics. Drugs baseduponoxytocin’sactionmaybe novelrmtipsychotics.