title: Secretin effects on cerebellar-dependent motor learning in schizophrenia.
abstract: OBJECTIVE
  Pervasive cognitive deficits in schizophrenia are a major cause of disability among individuals with the disorder. One such deficit is the loss of effective associative learning, which is readily assessed via eye-blink conditioning procedures. The authors examined the efficacy of secretin, a hormonal agonist for the prototype group B G-protein-coupled receptors, in ameliorating eye-blink conditioning deficits in schizophrenia patients.
  
  
  METHODS
  Immediately following a pretreatment delay eye-blink conditioning recording session, 25 individuals with schizophrenia received either secretin (RG1068; 20 microg/kg [N=15]) or a saline placebo (20 microg/kg [N=10]) subcutaneously in a double-blind fashion. Comparison groups were formed by yoking pairs of subjects on the basis of performance during the pretreatment baseline eye-blink conditioning recording session, and thus 20 subjects underwent further analysis. Secretin was selected because eye-blink conditioning depends on the release of Purkinje cell inhibition on deep nuclei of the cerebellum and recent findings indicate that secretin is endogenously released in the cerebellum, where it acts as a retrograde messenger and neuromodulator on basket and Purkinje cells.
  
  
  RESULTS
  Eye-blink conditioning was significantly improved at 2 and 24 hours after secretin administration but not after treatment with placebo. These results are consistent with evidence of intracellular signaling abnormalities in the pathophysiology of schizophrenia and indicate a possible role for secretin in modulating cerebellar-mediated classically conditioned learning.
  
  
  CONCLUSIONS
  If cerebellar abnormalities in individuals with schizophrenia are associated with fundamental mechanisms and symptoms of the disorder, as suggested by the cognitive dysmetria model, then cerebellar-targeted treatments may provide a novel approach to treatment for schizophrenia.
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, 1101 E. Tenth St., Bloomington, IN 47405, USA.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Bolbecker
authors.forename: William P
authors.initials: WP
authors.lastname: Hetrick
authors.forename: Jason K
authors.initials: JK
authors.lastname: Johannesen
authors.forename: Brian F
authors.initials: BF
authors.lastname: O'Donnell
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Steinmetz
authors.forename: Anantha S
authors.initials: AS
authors.lastname: Shekhar
mesh_terms: D000328:Adult; D001245:Association Learning / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology; D003215:Conditioning, Eyelid / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012633:Secretin / Q000627:therapeutic use*
chemical_list: D012633:Secretin