Attention refers to the processes determining an organism's receptivity to external or internal excitation and hence the probability that it will engage in the processing of that excitation (Parasuraman 1998). Although it is often related as a cognitive function, it is distinct in encompassing a multitude of manifestations that underlie and sustain the activity of the other cognitive and behavioral performance in several ways: through the selection and integration of sensory inputs, which is essential for efficient learning and remembering as well as for the organization of appropriate responses. Impaired attentional processing may therefore become manifested as inattention, distractibility, memory impairment, confusion, perseveration, or disinhibition. Recognition of the diversity of attention has led to the identification of three distinct fundamental qualities: selection, enabling the allocation of priority to certain informational elements to the exclusion of others; vigilance, referring to the capacity for attentional persistence over time; and control, which optimizes performance, for example, by inhibition of concurrent activities (Parasuraman 1998; Robbins 2002, 2005).

Attempts to uncover neural mechanisms through which brain serotonin systems influence attentional processes as well as other executive functions are complicated by the heterogeneity of the receptors through which serotonin acts. At least 14 distinct subtypes of serotonin (5-hydroxytryptamine, or 5-HT) receptors are expressed within the central nervous system (Barnes and Sharp 1999). They are highly diverse in respect to their structures, gene regulation, primary effect or mechanisms, regional and subcellular expression patterns and physiological actions. However, the multiplicity of 5-HT receptors provides an opportunity for a fine functional dissection of brain serotonin systems, one receptor at a time.

Experimental Psychology Laboratory, Department of Psychiatry, Athens University Medical School, Eginition Hospital, 74, Vas. Sofias Ave., 11528 Athens, Greece e-mail: [email protected]

G.Di Giovanni et al. (eds.), 5-HT2C Receptors in the Pathophysiology of CNS Disease, The Receptors 22, DOI 10.1007/978-1-60761-941-3_23, © Springer Science + Business Media, LLC 2011

Progress in this area has been facilitated by the development of relatively selective pharmacological tools and by molecular genetic techniques enabling the generation of animals with planned 5-HT receptor gene mutations. In order to ascertain neu-roanatomical and neurochemical specificity of experimental interventions, it is necessary to resort to the use of experimental animal models. This endeavor has been facilitated by the current availability of comparable cross-species tests of cognitive function. These enable the identification of common neural substrates that subserve similar functions across species, increasing the likelihood that the same cognitive functions are being studied in each species.

In this chapter, the contribution of the serotonergic system to basic operations such as vigilance, shifting, and executive control are surveyed with emphasis to a prominent central serotonin receptor subtype - the 5-HT2C receptor. Following a brief description of the anatomy of 5-HT2A and 5-HT2C receptor, the survey is focused on evidence from experimental animals. It encompasses data generated by four different experimental conditions, each of which centers on a specific aspect of the attentional and executive function.

The first paradigm is the five-choice serial reaction time task, which provides a direct measure of sustained attention and bears good analogy to the human continuous performance test (CPT), a traditional index of human vigilance. The second paradigm is attentional set shifting and reversal learning, which has been used to decompose the types of processes engaged by tests of attentional flexibility such as the Wisconsin Card Sort Test (WCST). The third paradigm is the reinforced spatial alternation measuring memory, cognitive flexibility, as well as persistent behavior. Finally, the signal attenuation paradigm models certain components of executive control, including attention and inhibition. In each case, the types of operation that are measured by the given paradigm will be defined. Then, the role of the seroton-ergic systems in the neurochemical modulation of its behavioral output will be examined, focusing on the contribution of the 5-HT2C receptor subtype. In conclusion, reference to clinical implications for neurological and neuropsychiatric disorders will be made.

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