In a mouse model of schizophrenia induced by phencyclidine, the order in which nicotine (a surrogate for smoking) is introduced matters for the behavioral outcomes. Nicotine given before phencyclidine potentiated locomotor sensitization, a behavior linked to psychosis. Nicotine given after phencyclidine worsened a schizophrenia-like deficit in pre-pulse inhibition, but only in male mice. Neither sequence affected rearing, a control behavior. The findings suggest that whether smoking precedes schizophrenia or vice versa produces distinct effects on the brain and behavior, which may help identify mechanisms underlying the high comorbidity between smoking and schizophrenia.
In adolescent mice, nicotine exposure did not worsen and may have even ameliorated psychotic-like behavior induced by phencyclidine, a model of psychosis. The antipsychotic drug raclopride prevented the development of this behavior, and nicotine temporarily boosted raclopride's inhibitory effect. Nicotine history shortened the expression of sensitized behavior after withdrawal. The findings suggest that nicotine may transiently improve the efficacy of antipsychotic medication through mechanisms involving dopamine D2 receptors.