Effects of acute intra-cerebral administration of the 5-HT2A/C receptor ligands DOI and ketanserin on impulse control in rats

Impulsivity or diminished inhibitory control of behavior (impulse control) is a prominent feature of several neuropsychiatric diseases. Serotonin (5-HT) plays an important role in impulse control. In order to examine the role of 5-HT2 receptors in a network comprising the orbitofrontal cortex (OFC) and the basolateral amygdala (BLA) in impulse control, the present study investigated effects of local infusions of the 5-HT2 receptor ligands DOI [(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride] and ketanserin on the performance of rats in the 5-choice serial reaction time task (5-CSRTT). Simultaneous bilateral infusion of the 5-HT2A/C receptor agonist DOI (5 μg/0.3 μl) into the OFC and the BLA significantly increased impulsive responding in the 5-CSRTT. These data suggest that both the OFC and the BLA are implicated in the mediation of DOI-induced impulsivity in the 5-CSRTT. Furthermore, these data support the notion that impulsivity caused by excessive 5-HT receptor stimulation is not mediated by just one particular brain structure, but rather by additive effects in at least two cortico-limbic structures, or perhaps by interactions of different transmitter systems within forebrain circuits.