Effects of acute systemic administration of serotonin2A/C receptor ligands in a delay-based decision-making task in rats

Serotonin (5-hydoxytryptamine; 5-HT) has been implicated in the regulation of impulsivity, and high levels of impulsive behavior are associated with certain neuropsychiatric disorders. An important aspect of impulsive behavior is the inability to tolerate delays in reward. This study investigated the effects of the 5-HT2A/C receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride] and the 5-HT2A receptor antagonist ketanserin on impulsive behavior measured in a delay-based decision-making task. Male Wistar rats were trained in a T-maze to choose a large but 10-s delayed food reward instead of a small immediate reward. After stable baseline performance (70% choice of large reward), the effects of acute systemic administration of 5-HT2A/C receptor ligands on waiting capacity were tested. Systemic administration of DOI (0.1, 0.3, and 0.5 mg/kg) impaired waiting capacity in a dose-dependent manner, whereas ketanserin had no effect. When combined with ketanserin, DOI did not impair waiting capacity. The data indicate that DOI-induced impairment of the ability to discount a delay in reward in a T-maze is probably regulated by 5-HT2A receptors. Furthermore, this study extends the existing findings of 5-HT2 receptor involvement in different tasks of delay aversion in rodents. Behavioural Pharmacology 20:415-423 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.