Post-drug consequences of chronic atypical antipsychotic drug administration on the ability to adjust behavior based on feedback in young monkeys

RATIONALE: Atypical antipsychotic drugs are characterized by their affinity for serotonin and dopamine receptors. The dopaminergic system undergoes developmental changes during childhood, making it vulnerable to external influences such as drug administration. OBJECTIVE: The purpose of this study was to assess the long-term effects of administering risperidone and quetiapine to 12–24-month-old macaque monkeys on cognitive development, a maturational equivalent to 4–8-year-old children. METHODS: Forty male pigtailed macaques were used in the study (n = 20 placebo, n = 10 risperidone, n = 10 quetiapine). Following a 4-month pre-drug period, animals were orally administered 2 mg/kg of quetiapine and .025 mg/kg of risperidone daily for 4 months, then the dosage was doubled for another 4 months. They were followed up for 4 months after cessation of the drug. Animals were assessed through all phases of the study on two-object discrimination and learning set. RESULTS: Cognitive development was not negatively affected while the animals were being administered the drug. However, the risperidone group had significant decrements in performance on the learning set task after cessation of the drug (p = 0.006, η (p)(2) = 0.59). Analysis of errors showed that the risperidone group had a significant increase in perseverative responding during the post-drug phase (p = 0.002, η (p)(2) = 0.67). CONCLUSION: As with human studies, neither risperidone nor quetiapine had a negative impact on cognitive development during the drug phases. However, the results show that the risperidone group had behavioral impairment post-drug, suggesting that the drug may have impacted the development of the dopaminergic system.