Dopamine agonists disrupt visual latent inhibition in normal males using a within-subject paradigm

Latent inhibition (LI) is the delayed learning of an association when the conditioned stimulus has previously been experienced out of the context of that association. LI can be measured across species and has been used to understand the neurobiology of schizophrenia, since some reports suggest that schizophrenia patients exhibit LI deficits. One challenge of LI studies in humans has resulted from the fact that LI paradigms have almost uniformly involved between-subject comparisons. We now report a new within-subject paradigm that detected LI in normal adult male subjects after ingestion of a placebo. After amphetamine (20 mg p.o.) or bromocriptine (1.25 mg p.o.), LI was not evident, suggesting that the LI detected by this paradigm is sensitive to disruption by dopamine agonists. The apparent advantages and limitations of this paradigm are discussed with regard to its future use in understanding the neural basis of reported LI deficits in schizophrenia.

[1]  C. Bradshaw,et al.  Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man , 1998, Journal of psychopharmacology.

[2]  R. Lubow Latent inhibition. , 1973, Psychological bulletin.

[3]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[4]  I. Weiner,et al.  The latent inhibition model of schizophrenia: Further validation using the atypical neuroleptic, clozapine , 1996, Biological Psychiatry.

[5]  David L. Braff,et al.  Latent inhibition in schizophrenia , 1996, Schizophrenia Research.

[6]  N. Swerdlow,et al.  Dopamine agonist effects on startle and sensorimotor gating in normal male subjects: time course studies , 2002, Psychopharmacology.

[7]  R. Lubow,et al.  Latent inhibition as a function of schizotypality and gender: implications for schizophrenia , 2002, Biological Psychology.

[8]  R. Lubow,et al.  Latent inhibition: the effect of nonreinforced pre-exposure to the conditional stimulus. , 1959, Journal of comparative and physiological psychology.

[9]  H. Norris The action of sedatives on brain stem oculomotor systems in man. , 1971, Neuropharmacology.

[10]  R. Lubow,et al.  Latent inhibition with a response time measure from a within-subject design: effects of number of preexposures, masking task, context change, and delay. , 2001, Neuropsychology.

[11]  D. Braff,et al.  51 ENDOPHENOTYPES IN STUDIES OF THE GENETICS OF SCHIZOPHRENIA , 2002 .

[12]  R. Lubow,et al.  Disruption of latent inhibition by acute administration of low doses of amphetamine , 1988, Pharmacology Biochemistry and Behavior.

[13]  N. Gray Abolition of latent inhibition in acute, but not chronic, schizophrenics , 1992 .

[14]  An empirical analysis of the super-latent inhibition effect , 2002, Animal learning & behavior.

[15]  N. Swerdlow,et al.  Effects of caffeine on sensorimotor gating of the startle reflex in normal control subjects: impact of caffeine intake and withdrawal , 2000, Psychopharmacology.

[16]  K. Hutchison,et al.  Personality factors moderate subjective and psychophysiological responses to d-amphetamine in humans. , 1999, Experimental and clinical psychopharmacology.

[17]  R. Lubow,et al.  Latent inhibition and schizophrenia , 1987 .

[18]  J. Gray,et al.  Differential Performance of Acute and Chronic Schizophrenics in a Latent Inhibition Task , 1988, The Journal of nervous and mental disease.

[19]  A. Bond,et al.  The use of analogue scales in rating subjective feelings , 1974 .

[20]  J. Servais,et al.  Étude des effets subjectifs de l'amphétamine chez l'homme en fonction de la personnalité , 2004, Psychopharmacologia.

[21]  J. Gray,et al.  Latent inhibition and “psychotic proneness” in normal subjects , 1988 .

[22]  J. Gray,et al.  Integrating schizophrenia. , 1998, Schizophrenia bulletin.

[23]  N. Swerdlow,et al.  Effects of amantadine and bromocriptine on startle and sensorimotor gating: parametric studies and cross-species comparisons , 2002, Psychopharmacology.

[24]  S. Potkin,et al.  Structured Interview for Assessing Perceptual Anomalies (SIAPA). , 1999, Schizophrenia bulletin.

[25]  J. Rawlins,et al.  Reduced latent inhibition in people with schizophrenia: an effect of psychosis or of its treatment , 1998, British Journal of Psychiatry.

[26]  J. Gray,et al.  Abolition of latent inhibition by a single 5 mg dose ofd-amphetamine in man , 1992, Psychopharmacology.

[27]  Dragan M. Svrakic,et al.  The Tridimensional Personality Questionnaire: U.S. Normative Data , 1991, Psychological reports.

[28]  N. Swerdlow,et al.  Enhanced visual latent inhibition in obsessive–compulsive disorder , 1999, Biological Psychiatry.