Ready-to-use models

Serotonin Transporter Knock-out rats:

a new model for anxiety and depression

• Complete inactivation of Serotonin Transporter (SERT) protein
• Main phenotypes already described

No SERT transcript in Serotonin transporter Knock-out rat: Figure 1: Northern blot analysis of the SERT transcript in the Raphe Nuclei of a SERT+/+, SERT+/- and SERT-/- rats	No change in other non-serotonergic transporter activity and neuro transmitter levels
No SERT protein in Serotonin transporter Knock-out rat: Figure 2: Representative [3H]citalopram auto radiograms of 16 µm coronal sections of SERT+/+, SERT+/- and SERT-/- rats	Animals appear healthy and breed normally

SERT Knock-out rats consistently displayed increased levels of anxiety- and depression-like behaviors. SERT Knock-out rats spent less time in the center part of the open field (Figure 1) as well as on the open arms of the elevated plus maze, suggestive of an enhanced level of anxiety.

Figure 1: Anxiety. Behavior was recorded for 5 min in SERT +/+ and SERT -/- male and female rats in the open field test (A) and elevated plus maze (EPM) test (B). Data are expressed as Mean +/- S.E.M. time (s) spent in the center of the open field or on the open/closed arms of the elevated plus maze (males: n12 SERT +/+ and n12 SERT -/- rats; females: n12 SERT +/+ and n12 SERT -/- rats; * P0.05) From Neuroscience. 2008: A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders. Olivier JD et al.

Serotonin transporter deficiency increases abdobminal fat in female, but not male rats. Depression and abdominal obesity often co-occur, predominantly in women. Female, but not male, depression-prone serotonin transporter knockout rats had a strong increase (54%) in abdominal fat (Figure 2), whereas no increases in plasma concentrations of glucose and insulin were observed.

Figure 2: Mesenteric (MWAT), perirenal (PWAT), and subcutaneous white adipose tissue (SWAT) in female SERT-/- and SERT+/+ rats on standard chow only and on the HFHS-choice diet. Data are expressed as mean +/- S.E.M. % fat of fat. # P < 0.05; female SERT-/- different from female SERT+/+. *P < 0.05; animals of same sex and genotype different on standard chow compared to HFHS-choice diet. HFHS, high-fat, high-sucrose From Obesity (Silver Spring) 2010: Serotonin transporter deficiency increases abdominal fat in female, but not male rats. Homberg JR et al.

Endophenotypes:

• Increased in anxiety and long-term decision making
• Decreased in impulsivity and impulsivity-related social behaviour (aggression and play)
• No change in novelty-induced locomotor activity, cognitive flexibility and attention

Disease-related phenotypes:

• Increased depression-like behaviour
• Increased cocaine self-administration, increased cocaine-induced conditioned place preference, increased cocaine-induced hyperactivity
• Decreased alcohol intake

Metabolism:

• Female-specific reduced body weight
• Serotonin is absent in blood platelets but this does not result in a change in blood pressure, basal and L-NNA-evoked

Rat line information:

• Genetic background is Wistar
• Rat delivered are SPF / VAF (Specific Pathogen Free/Virus and Antibody Free conditions) certified by Charles River

References:

• Serotonin transporter deficiency increases abdominal fat in female, but not male rats. Homberg JR et al. Obesity (Silver Spring). 2010
• Orbitofrontal cortex and amygdalar over-activity is associated with an inability to use the value of expected outcomes to guide behaviour in serotonin transporter knockout rats. Nonkes LJP et al. Neurobiology of Learning and Memory 2010
• Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats. Homberg JR et al. Psychopharmacology (Berl). 2008
• Serotonin transporter dosage modulates long-term decision-making in rat and human. Homberg JR et al. Neuropharmacology. 2008
• A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders. Olivier JD et al. Neuroscience. 2008
• Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibility. Homberg JR et al. Eur J Neurosci. 2007
• Characterization of the serotonin transporter knockout rat: a selective change in the functioning of the serotonergic system. Homberg JR et al.Neuroscience. 2007