The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine
Behavioural Pharmacology June 1, 2022 José Eduardo Suárez-Santiago, Gabriel Roldán Roldán, Ofir Picazo Picazo
Ketamine, an anesthetic that blocks NMDA receptors, can produce symptoms resembling schizophrenia. In mice, five daily injections of ketamine (10 mg/kg) caused memory deficits, anxiety, obsessive-compulsive behaviors, and stereotyped movements. Two experimental drugs targeting the 5-HT6 receptor—an agonist (E-6837) and an antagonist (SB-271046)—each reversed the memory impairment and reduced anxiety when given alone. SB-271046 also decreased climbing behavior. Neither drug affected the light–dark test. Unexpectedly, when either drug was combined with ketamine, anxiety worsened. Both types of 5-HT6 drugs appear to modulate psychotic-like symptoms caused by blocking NMDA receptors.