Abstract
Latent inhibition (LI) is a behavioral phenomenon whereby repeated exposure to a non-reinforced stimulus retards subsequent conditioning to that stimulus. Deficits in LI may reflect an inability to ignore irrelevant stimuli and are studied as a model of the cognitive/attentional abnormalities found in schizophrenia. We recently determined that pretreatment with escalating doses of the indirect dopamine agonist amphetamine (AMPH; 3 daily injections ip, 1-5 mg/kg, over 6 days) disrupts LI in rats tested in a 2-way active avoidance paradigm during withdrawal. In the present study, we evaluated the effects of the atypical neuroleptic clozapine and the typical neuroleptic haloperidol on the expression of LI on day 4 of AMPH withdrawal. Neuroleptic injections were given either 45 min prior to each of two tone preexposure sessions and a subsequent tone-shock avoidance test session, or only prior to the test session. As expected, saline-injected control groups showed LI during the test session, as reflected by significantly reduced avoidance in tone preexposed vs. non-preexposed rats. In contrast, animals pretreated with escalating doses of AMPH did not show LI, due to the improved avoidance of the preexposed animals. Both haloperidol (0.03 mg/kg) and clozapine (5 mg/kg) largely reversed the disruptive influence of AMPH on LI regardless of whether these drugs were administered prior to both preexposure and test sessions or only prior to the test session. These results provide pharmacological validation for an AMPH withdrawal model of schizophrenic symptoms.
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Acknowledgements
This study was supported by the Swiss Federal Institute of Technology (ETH-Zurich, Switzerland). We would like to thank the staff of the animal facility for their care and maintenance of the animals used in this study, Mr. Peter Schmid for his valuable technical assistance, and Mrs. Bonnie Strehler for her secretarial help.
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Russig, H., Murphy, C. & Feldon, J. Clozapine and Haloperidol Reinstate Latent Inhibition Following its Disruption during Amphetamine Withdrawal. Neuropsychopharmacol 26, 765–777 (2002). https://doi.org/10.1016/S0893-133X(01)00422-5
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DOI: https://doi.org/10.1016/S0893-133X(01)00422-5
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