The present experiments investigated clozapine (2.5, 5 and 10 mg/kg) and haloperidol (0.1 mg/kg) administration on latent inhibition (LI) in rats. Clozapine's ability to antagonize amphetamine-induced disruption of LI was also assessed. A conditioned emotional response procedure was employed. In the pre-exposure stage, 'pre- exposed' rats received 10 (Experiment 1) or 40 (Experiment 2) presentations of a flashing light stimulus without reinforcement. During the conditioning phase, the light stimulus was paired with a footshock. At test, LI was expressed by the extent of suppression of water licking during flashing light presentation. Both clozapine (10 mg/kg) and haloperidol (0.1 mg/kg) significantly facilitated LI. In addition, clozapine significantly reversed the disruption of LI induced by amphetamine (1.0 mg/kg). These results with clozapine illustrate that LI is sensitive to antipsychotics which differ in their mode of action and furthermore emphasize the value of LI as a test model for detecting the antipsychotic potential of novel drugs.
Baruch I., Hemsley D.R., Gray JA ( 1988) Differential performance of acute and chronic schizophrenics in a latent inhibition task. J Nerv Ment Dis176: 598-605
2.
Bruhwyler J., Chleide E., Mercier M. (1990) Clozapine: an atypical neuroleptic. Neurosci Biobehav Rev14: 357-363
3.
Cassaday H.J., Hodges H., Gray JA ( 1993) The effects of ritanserin. RU 24969 and 8-OH-PAT on latent inhibition in the ratJ Psychopharmac7: 63-67
4.
Christison E.G., Atwater G.E., Dunn L.A., Kitts C.D. (1988) Haloperidol enhancement of talent inhibition: Relation to therapeutic action? Biol Psychiat23: 746-749
5.
Christison G.W., Le AT, Baton R., Matheson D. (1991) Latent inhibition-based animal models—implications of effects of phencyclidine and clozapine. Schizophr Res4: 331-332
6.
Coward D.M., Imperato A., Urwyler S., White T.G. (1989) Biochemical and behavioural properties of clozapine . Psychopharmacology99: S6-S12
7.
Dunn L.A., Atwater G.E., Kilts C.D. (1993) Effects of antipsychotic drugs on latent inhibition: sensitivity and specificity of an animal behavioral model of clinical drug action. Psychopharmacology112: 315-323
8.
Farde L., Wiesel F.A., Nordström A.L., Sedvall G. (1989) D1 and D2 dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology99: 28-31
9.
Feldon J., Weiner I. (1991) The latent inhibition model of schizophrenic attention disorder: haloperidol and sulpiride enhance rats'ability to ignore irrelevant stimuli. Biol Psychiat29: 635-646
10.
Kane J., Honigfeld G., Singer J., Meltzer H. (1988) The clozaril collaborative study group clozapine for the treatment-resistant schizophrenic-a double blind study with chlorpromazine . Archs Gen Psychiat45: 789-796
11.
Kerwin R.W. (1994) The new atypical antipsychotics: a lack of extrapyramidal side-effects and new routes in schizophrenia research. Br J Psychiat164: 141-148
12.
Killcross A.S., Robbins T.W. (1993) Differential effects of intraaccumbens and systemic amphetamine on latent inhibition using an on-baseline within-subject conditioned suppression paradigm. Psychopharmacology110: 479-489
13.
Kurz M., Hummer M., Oberbauer H., Fleischhacker W.W. (1995) Extrapyramidal side-effects of clozapine and haloperidol . Psychopharmacology118: 52-56
14.
Lubow R.E. (1989) Latent inhibition and conditioned attention theory . Cambridge University Press, Cambridge
15.
Mackintosh NJ (1983) Conditioning and associative learning. Oxford University Press, New York
16.
Matz R., Rick W., Oh D., Thompson H., Gershon S. (1974) Clozapine—a potential antipsychotic agent without extrapyramidal manifestation. Curr Ther Res16: 687-695
17.
Meltzer H.Y., Bastani B., Ramirez L., Matsubara S. (1989) Clozapine: new research on efficacy and mechanism of action. Eur Archs Psychiat Neurol Sci238: 332-339
18.
Moran PM, Fischer T.R., Hitchcock J.M., Moser P.C. (1996) Effects of clozapine on latent inhibition in the rat. Behav Pharmac7: 42-48
19.
Peters S.L., Joseph M.H. (1993) Haloperidol potentiation of latent inhibition in rats: evidence for a critical role at conditioning rather than pre-exposure . Behav Pharmac4: 183-186
20.
Schotte A., Janssen P F M, Megens A A H P, Leysen J.E. (1993) Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography. Brain Res631:191-202
21.
Solomon P.R., Crider A., Winkelman J.W., Turi A., Kamer R.M., Kaplan L.J. (1981) Disrupted latent inhibition in the rat with chronic amphetamine or haloperidol-induced supersensitivity: relationship to schizophrenic attention disorder. Biol Psychiat16: 519-537
22.
Trimble K.M., Bell R., King D.J. (1997) Enhancement of latent inhibition in the rat by the atypical antipsychotic agent remoxipride. Pharmac Biochem Behav56: 809-816.
23.
Van Tol H H M, Bunzow J.R., Guan H., Sunahara R.K., Seeman P., Niznik H.B., Civelli O. (1991) Cloning of the gene for a human dopamine D 4 receptor with high affinity for the antipsychotic clozapine. Nature350: 610-614
24.
Weiner I. (1990) Neural substrates of latent inhibition: the switching model. Psychol Bull108: 442-461
25.
Weiner I., Feldon J. (1987) Facilitation of latent inhibition by haloperidol in rats. Psychopharmacology91: 248-253
26.
Weiner I., Feldon J. (1994) The latent inhibition model of schizophrenic attention disorder and of antipsychotic drug action: comment on Dunn, Atwater and Kitts. Psychopharmacology116: 379-380.
27.
Weiner I., Lubow R.E., Feldon J. (1981) Chronic amphetamine and latent inhibition. Behav Brain Res2: 285-286
28.
Weiner I., Lubow R.E., Feldon J. (1984) Abolition of the expression but not the acquisition of latent inhibition by chronic amphetamine in rats. Psychopharmacology83: 194-199
29.
Weiner I., Lubow R.E., Feldon J. (1988) Disruption of latent inhibition by acute administration of low doses of amphetamine. Pharmac Biochem Behav30: 871-878
30.
Weiner I., Kidron R., Tarrasch R., Arnt J., Feldon J. (1994) The effects of the new antipsychotic sertindole on latent inhibition in rats. Behav Pharmac5:119-124
31.
Weiner I., Traub A., Rawlins J N P, Smith A.D., Feldon J. (1995) The sigma ligand BMY-14802 as a potential antipsychotic:evidence from the latent inhibition model in rats. Behav Pharmac6: 46-54
32.
Weiner I., Shadach E., Tarrasch R., Kidron R., Feldon J. (1996) The latent inhibition model of schizophrenia: further validations using the atypical neuroleptic, clozapine. Biol Psychiat40: 834-843
