Cognitive enhancement treatments

Cognitive enhancing effects of 5-HT3 receptor antagonists have been observed in several animal models, using both normal animals and animals in which a cognitive deficit has been induced by the administration of the muscarinic antagonist scopolamine [41]. An example is the Wisconsin test, in which marmosets learn to discriminate which of two objects conceal a food reward and, after learning this, the task is reversed such that the food is hidden beneath the other object. Treatment with ondansetron has been shown to enhance the ability of marmosets to learn the reversal task. 

Zangara A. (2003) The psychopharmacology of huperzine A An alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer s disease. Pharmacol BiochemBehav 75 675-686. 

To reveal the cognition-enhancing potential of the S-HTj antagonists, studies in age-related memory impairment have been carried out with psy-chiatrically healthy subjects impaired with scopolamine and patients with dementia. In a randomized double-blind, double-dummy, four-way crossover study in a small number of subjects, each psychiatrically healthy male subject received placebo, scopolamine [0.4 mg im], scopolamine plus alosetron [10 J,g iv], or alosetron [250 Jg] [Preston 1994 Preston et al. 1991). Assessments of verbal and spatial memory, sedation, and sustained attention were performed before and after treatment. The main results from the study were that scopolamine induced robust deficits on all primary variables measured, the reduction in verbal and spatial memories being attenuated by 10- Jg and 250- Jg doses of alosetron, respectively. No effects on the sedation or on changes in attention were noted. 

In this chapter, we use the term cognitive enhancers to refer to two classes of pharmacological agents used in the treatment of Alzheimer s disease the cholinesterase inhibitors and the A-methyl-D-aspartate (NMDA) receptor antagonists. 

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