Background Attentional deficits accompany many psychiatric disorders, underscoring the need for rodent models of attention to screen novel therapeutic agents and characterize the biological basis of attention. The five-choice serial reaction time task (5CSRTT) is one such model. Here, we characterized the effects of four standard psychotropic agents on performance in the 5CSRTT. Methods Male Sprague-Dawley rats were trained in the 5CSRTT (5-sec inter-trial interval and .5-sec stimulus duration) until they reliably performed at > 60% accuracy and < 20% omissions. They were then treated systemically with the stimulant methylphenidate (MPH) (.063–2.0 mg/kg), the N -methyl-D-aspartate antagonist dizocilpine (MK-801) (.008–.25 mg/kg), the norepinephrine reuptake inhibitor desipramine (DMI) (.63–10 mg/kg), or the κ-receptor agonist U69,593 (.25–2.0 mg/kg) 30 min before testing. Results Methylphenidate (.5 mg/kg) increased accuracy. Dizocilpine impaired accuracy (.25 mg/kg), increased premature responses (.063–.25 mg/kg), and increased omissions (.25 mg/kg). Desipramine decreased premature responses (5.0 mg/kg) but increased omissions (10 mg/kg), correct response latencies (5.0–10.0 mg/kg), and reward latencies (5.0–10.0 mg/kg). The κ-opioid agonist U69,593 (1.0–2.0 mg/kg) increased omissions and correct response latencies. Conclusions In Sprague-Dawley rats, psychotropic drugs with distinct pharmacological profiles produced distinguishable effects in the 5CSRTT. The effects of these classes of drugs under our testing conditions are qualitatively similar to their effects in humans.