Individual phenotype predicts nicotine-haloperidol interaction in catalepsy: Possible implication for the therapeutic efficacy of nicotine in Tourette's syndrome

Abstract

In individuals with Tourette's syndrome, the therapeutic efficacy of haloperidol can be augmented by nicotine. In laboratory rats, the dopamine antagonist haloperidol produces catalepsy and nicotine can potentiate it, although this effect is variable and not always observed. Our aim was to understand this variability. In rats, the locomotor response to a novel environment predicts the magnitude of the locomotor response to nicotine. Since the psychostimulant effect of nicotine might counter catalepsy, we hypothesized that rats with a high locomotor response to novelty would show reduced vulnerability to nicotine potentiation of haloperidol catalepsy. First, we administered haloperidol (0, 0.1 or 0.3mg/kg, ip) and found stronger catalepsy in rats with low reactivity to novelty. Second, we administered haloperidol (0.3mg/kg) or haloperidol plus nicotine (0.1mg/kg, ip) and found that nicotine indeed potentiated haloperidol catalepsy but only in rats with low reactivity to novelty. Nicotine did not induce catalepsy on its own. Thus, previously reported inconsistencies in the catalepsy potentiating effect of nicotine may have been due to differential vulnerability to its stimulant actions. As previously observed, the potentiation of haloperidol catalepsy was greatest 4h after injection. Given the short half-life of nicotine, the mechanism(s) underlying the delayed expression of its pro-cataleptic capacity remains obscure.