title: Peripherally administered oxytocin modulates latent inhibition in a manner consistent with antipsychotic drugs.
abstract: BACKGROUND
  Peripherally administered oxytocin (OT) has produced antipsychotic drug (APD)-like effects in animal tests that are predictive of APD efficacy. However, these effects have mainly been demonstrated using animal models of schizophrenia-like deficits in prepulse inhibition (PPI) of the startle reflex. Another schizophrenia-relevant abnormality that is the basis of a predictive animal test for APD efficacy is deficient latent inhibition (LI). LI is the normal suppression of a classically conditioned response when the subject is pre-exposed to the conditioned stimulus (CS) before it is paired with the unconditioned stimulus (UCS). Conditioned taste aversion (CTA), the normal avoidance of ingesting a food or liquid by animals when its taste is associated with an aversive experience, was used to test whether OT facilitates LI consistent with APDs.
  
  
  METHODS
  Brown Norway rats, known to naturally display attenuated LI, were aversively conditioned on two consecutive exposures to flavored drinking water (0.1% saccharin) by pairing it with malaise-inducing lithium chloride injections. Concurrent with conditioning, rats received subcutaneous OT (0.02, 0.1, 0.5mg/kg) or saline. Some rats were pre-exposed to the flavored water prior to its aversive conditioning (pre-exposed) while others were not (non pre-exposed). Two days after aversive conditioning the amount of flavored water consumed during a 20-min session was recorded.
  
  
  RESULTS
  As expected, LI, defined as greater consumption by pre-exposed vs. non pre-exposed rats was only weakly exhibited in Brown Norway rats and OT enhanced LI by reducing CTA in pre-exposed rats in a dose-dependent manner, with the 0.02 mg/kg dose producing the strongest effect.
  
  
  CONCLUSIONS
  The facilitation of LI by OT is consistent with the effects produced by APDs and provides further support for the notion that OT has therapeutic potential for schizophrenia.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, United States. Electronic address: dfeifel@ucsd.edu.
authors.forename: D
authors.initials: D
authors.lastname: Feifel
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: P D
authors.initials: PD
authors.lastname: Shilling
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: J
authors.initials: J
authors.lastname: Hillman
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: M
authors.initials: M
authors.lastname: Maisel
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: J
authors.initials: J
authors.lastname: Winfield
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, United States.
authors.forename: G
authors.initials: G
authors.lastname: Melendez
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001362:Avoidance Learning / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005508:Food Deprivation; D007266:Inhibition, Psychological; D018021:Lithium Chloride / Q000494:pharmacology; D010121:Oxytocin / Q000008:administration & dosage*; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D010121:Oxytocin; D018021:Lithium Chloride
keywords: Animal models; Antipsychotic drugs; Latent inhibition; Oxytocin; Schizophrenia