Low dose quetiapine reverses deficits in contextual and cued fear conditioning in rats with excitotoxin-induced hippocampal neuropathy

Previous studies have demonstrated that adult rats with excitotoxic lesions of the hippocampus display deficits in memory-related behaviors similar to the memory deficits associated with schizophrenia. In this study, we assessed the sub-chronic effects of quetiapine, risperidone and haloperidol on performance deficits after intracerebroventricular administration of the excitotoxin, kainic acid, using paradigms for contextual and cued fear conditioning and spatial reversal learning in rats. The effects of three doses of quetiapine (5, 10 and 20 mg/kg) and single doses of risperidone (0.5 mg/kg) and haloperidol (0.15 mg/kg) were compared. Quetiapine administration at the lowest dose (5 mg/kg) reversed deficits in contextual and cued fear conditioning, but not deficits in spatial reversal learning, in kainic acid-treated animals. However, the two higher doses of quetiapine, and the single doses of risperidone and haloperidol, did not reverse any of the kainic acid-induced behavioral deficits. These results may be relevant to the effects of quetiapine and other antipsychotic drugs on memory deficits in patients with schizophrenia.