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Abstract
Serotonin (5-HT) plays a crucial role in the brain, modulating mood, cognition and
reward. The serotonin transporter (SERT) is responsible for the reuptake of 5-HT from
the synaptic cleft and regulates serotonin signaling in the brain. In humans, SERT
genetic variance is linked to the pathogenesis of various psychiatric disorders, including
anxiety, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD).
Rodent self-grooming is a complex, evolutionarily conserved patterned behavior relevant
to stress, ASD and OCD. Genetic ablation of mouse Sert causes various behavioral deficits,
including increased anxiety and grooming behavior. The hallucinogenic drug lysergic
acid diethylamide (LSD) is a potent serotonergic agonist known to modulate human and
animal behavior. Here, we examined heterozygous Sert(+/-) mouse behavior following
acute administration of LSD (0.32 mg/kg). Overall, Sert(+/-) mice displayed a longer
duration of self-grooming behavior regardless of LSD treatment. In contrast, LSD increased
serotonin-sensitive behaviors, such as head twitching, tremors and backwards gait
behaviors in both Sert(+/+) and Sert(+/-) mice. There were no significant interactions
between LSD treatment and Sert gene dosage in any of the behavioral domains measured.
These results suggest that Sert(+/-) mice may respond to the behavioral effects of
LSD in a similar manner to wild-type mice.