title: Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibility.
abstract: Impulsivity and aggression have been suggested to inversely correlate with central serotonin (5-HT) levels in a trait-like manner. However, this relationship is far from straightforward. In the present study we addressed the effect of lifelong reduced or absent serotonin transporter (SERT) function, which is associated with constitutively increased extracellular 5-HT levels, on impulsivity and aggression. We used unique SERT knockout rats in a resident-intruder test, five-choice serial reaction time task and serial reversal learning task to assay aggression, inhibitory control and behavioural flexibility, respectively. Homozygous SERT knockout rats (SERT( -/-)) displayed reduced aggression and improved inhibitory control, but unchanged behavioural flexibility. The behavioural phenotype of heterozygous SERT knockout rats (SERT( +/-)) was not different from that of wild-type controls in any of the behavioural paradigms. We determined monoamine (metabolite) tissue levels in the medial prefrontal cortex, orbitofrontal cortex, lateral hypothalamus, raphe nuclei and cerebrospinal fluid, and found that the 5-HT levels, but not other monoamine tissue levels, were reduced in SERT( -/-) rats. In addition, the 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio in cerebrospinal fluid was increased in these rats. In conclusion, our data show that the absence of the SERT affects aggression and inhibitory control, but not behavioural flexibility, characteristics that may reflect the trait-like consequences of constitutive changes in central 5-HT levels.
authors: Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
authors: Judith R
authors: JR
authors: Homberg
authors: Tommy
authors: T
authors: Pattij
authors: Mieke C W
authors: MC
authors: Janssen
authors: Eric
authors: E
authors: Ronken
authors: Sietse F
authors: SF
authors: De Boer
authors: Anton N M
authors: AN
authors: Schoffelmeer
authors: Edwin
authors: E
authors: Cuppen
mesh_terms: D000374:Aggression / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism; D002755:Choice Behavior / Q000502:physiology; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007266:Inhibition, Psychological; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000235:genetics; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid