TY - JOUR
T1 - Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibility
AU - Homberg, Judith R.
AU - Pattij, Tommy
AU - Janssen, Mieke C.W.
AU - Ronken, Eric
AU - De Boer, Sietse F.
AU - Schoffelmeer, Anton N.M.
AU - Cuppen, Edwin
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
KW - 5-CSRTT
KW - 5-HIAA
KW - Aggression
KW - Knockout
KW - Reversal learning
UR - http://www.scopus.com/inward/record.url?scp=34848849006&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/j.1460-9568.2007.05839.x
DO - https://doi.org/10.1111/j.1460-9568.2007.05839.x
M3 - Article
C2 - 17897403
SN - 0953-816X
VL - 26
SP - 2066
EP - 2073
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 7
ER -