RATIONALE: Maladaptive impulsivity is symptomatic of several neuropsychiatric disorders including schizophrenia, attention-deficit hyperactivity disorder (ADHD), and substance abuse disorders; paradigms designed to assess the underlying neurobiology of this behavior are essential for the discovery of novel therapeutic agents. Various models may be used to assess impulsivity as measured by the five-choice serial reaction time task (5-CSRTT), including variable inter-trial interval (ITI) sessions, the selection of extreme high and low impulsivity phenotypes from a large outbred population of rats, as well as pharmacological challenges. OBJECTIVES: The aim of this study is to evaluate if pharmacological challenge models for impulsivity are biased by underlying differences in impulsivity phenotype. METHODS: Extreme high and low impulsivity phenotypes were selected in the 5-CSRTT, and dose-dependent effects of various pharmacological challenges, namely MK-801, yohimbine, and cocaine, were evaluated on task performance, specifically accuracy and premature responses. RESULTS: All three compounds increased premature responding, while a decrease in attentional performance occurred following MK-801 and yohimbine administration. No differences in drug-induced impulsivity between rats selected for high or low impulsivity or in parameters indicative of attentional performance could be determined. CONCLUSIONS: Our findings indicate that different pharmacological challenges increase impulsivity on the 5-CSRTT, with modest effects on attention. These effects were not influenced by underlying differences in impulsivity phenotype, which is an important prerequisite to reliably use these challenge models to screen and profile compounds with putative anti-impulsive characteristics.