Cognitive impairment is very prevalent in
schizophrenia and is currently undertreated in most patients. Attentional deficit is one of the hallmark symptoms of
schizophrenia.
Antipsychotic drugs, which can be quite effective in combating
hallucinations are often ineffective in reducing
cognitive impairment and can potentiate
cognitive impairment. Previously, we found that the
antipsychotic drug clozapine impaired, while
nicotine improved, the accuracy of rats performing a visual signal detection attentional task in normal rats. For the current study, in a model of
cognitive impairment of
schizophrenia with the
NMDA antagonist
dizocilpine (0.05 mg/kg), we examined the effects of
clozapine and
nicotine on significantly impaired attentional hit accuracy. This
dizocilpine-induced impairment was significantly (p<0.05) reversed by either
clozapine (1.25 mg/kg) or
nicotine (0.025 mg/kg). Interestingly, when
clozapine and
nicotine were given together, they blocked each other's beneficial effects. When the effective doses of 1.25 mg/kg
clozapine and 0.025 mg/kg
nicotine were given together the combination no longer significantly reversed the
dizocilpine-induced hit-accuracy impairment. Given that the great majority of people with
schizophrenia smoke, the potential beneficial effects of
clozapine on attentional function may be largely blocked by self-administered
nicotine. In addition, there are promising results concerning the development of nicotinic treatments to reverse cognitive deficits including attentional impairment. This is supported in the current study by the reversal of the
dizocilpine-induced attentional impairment by
nicotine. However, in
schizophrenia the efficacy of nicotinic treatments may be limited by co-treatment with
antipsychotic drugs like
clozapine. It will be important to determine which of the complex effects of
clozapine and
nicotine are key in reversing attentional impairment and how they block each other's effects for the development of
therapy to combat the attentional impairment of
schizophrenia.