Effects of LSD on grooming behavior in serotonin transporter heterozygous (Sert⁺/⁻) mice

Behav Brain Res. 2016 Jan 1:296:47-52. doi: 10.1016/j.bbr.2015.08.018. Epub 2015 Sep 1.


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.

Keywords: Grooming; Hallucinogens; Lysergic acid diethylamide; Serotonin transporter.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Grooming / drug effects*
  • Grooming / physiology
  • Lysergic Acid Diethylamide / administration & dosage
  • Lysergic Acid Diethylamide / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Plasma Membrane Transport Proteins / physiology*
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology*
  • Serotonin Syndrome / chemically induced*


  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Receptor Agonists
  • Slc6a4 protein, mouse
  • Lysergic Acid Diethylamide