Psychopharmacology (2004) 174: 86–98 DOI 10.1007/s00213-004-1805-y REVIEW Y. Chudasama . T. W. Robbins Psychopharmacological approaches to modulating attention in the five-choice serial reaction time task: implications for schizophrenia Received: 15 September 2003 / Accepted: 11 January 2004 / Published online: 8 April 2004 # Springer-Verlag 2004 Abstract Rationale: In schizophrenia, attentional dis- turbance is a core feature which may not only accompany the disorder, but may precede the onset of psychiatric symptoms. Objectives: The five-choice serial reaction time task (5CSRTT) is a test of visuo-spatial attention that has been used extensively in rats for measuring the effects of systemic and central neurochemical manipulations on various aspects of attentional performance, including selective attention, vigilance and executive control. These findings are relevant to our understanding of the neural systems that may be compromised in patients with schizophrenia. Methods: The 5CSRTT is conducted in an operant chamber that has multiple response locations, in which brief visual stimuli can be presented randomly. Performance is maintained using food reinforcers to criterion levels of accuracy. Various aspects of perfor- mance are measured, including attentional accuracy and premature responding, especially under different atten- tional challenges. Results: The effects of systemic and intra-cerebral infusions of selective dopamine, serotonin and cholinergic receptor agents on the 5CSRTT are reviewed with a view to identifying attention-enhancing effects that may be relevant to the treatment of cognitive deficits in schizophrenia. In addition, some novel agents such as modafinil and histamine receptor agents are also considered. Examining the effects of selective neurochem- ical lesions helped define the neural locus of attentional effects. Similarly, findings from microdialysis studies helped identify the extracellular changes in neurotrans- mitters and their metabolites in freely moving rats during performance of the 5CSRTT. Conclusions: The mono- aminergic and cholinergic systems have independent but complementary roles in attentional function, as measured by the 5CSRTT. These functions are predominantly under the control of the prefrontal cortex and striatum. These conclusions are considered in the context of their application towards therapeutic approaches for attentional disturbances that are typically observed in schizophrenic patients. Keywords Attention . Rat . Schizophrenia . Dopamine . Serotonin . Acetylcholine . Noradrenaline . Striatum . Prefrontal cortex . 5CSRTT Introduction Attentional deficits in schizophrenia have been investi- gated intensively since Bleuler (1950) and Kraepelin’ s (1971) accounts of attentional disturbances in their patients Nevertheless, impaired attentional processing has only recently gained respectability as one of the core deficits in this most elusive disorder. Attentional dis- turbances are grossly evident in encounters with schizo- phrenic patients: not only do attentional deficits accom- pany the disorder, they may have causal roots in the natural progression of subtle cognitive impairments that may precede the onset of the psychiatric symptoms (Jones et al. 1994; an der Heiden and Hafner 2000). Typically, patients with schizophrenia are unable to select and interpret incoming sensations leading to inappropriate responding. They find it difficult to sustain and shift attention in response to situational demands and illogically leap from one subject to another mid-conversation. At other times, they may orient to or fixate on trivial aspects of the environment, or perhaps engage compulsively in some activity. Furthermore, patients with flattened affect are typically unable to direct and sustain attention to emotionally meaningful goals and events. Indeed, autisti- cally withdrawn schizophrenics are essentially unaware of Y. Chudasama (*) National Institute of Mental Health, Building 49, Room 1B80, Convent Drive, Bethesda, MD 20892, USA e-mail: Yogita@ln.nimh.nih.gov Tel.: +1-301-4965625 Fax: +1-301-4020046 T. W. Robbins Cambridge University, Department of Experimental Psychology, Downing Street, Cambridge, CB2 3EB, UK