Effects of acute intra-cerebral administration of the 5-HT(2A/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-HT(2A/C) receptor agonist DOI (5 microg/0.3 microl) 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.
Hadamitzky
Martin
M
University of Bremen, Brain Research Institute, Department of Neuropharmacology, Center for Cognitive Sciences, COGNIUM, PO Box 330440, 28334 Bremen, Germany. mhadamitzky@ucsd.edu
Koch
Michael
M
D000679:Amygdala / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D005625:Frontal Lobe / Q000187:drug effects; D007175:Impulsive Behavior / Q000188:drug therapy*; D007215:Indophenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D008845:Microinjections; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D008024:Ligands; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; D007215:Indophenol; D007650:Ketanserin