The role of serotonin in the NMDA receptor antagonist models of psychosis and cognitive impairment.
Psychopharmacology February 1, 2011 Herbert Y Meltzer, Masakuni Horiguchi, Bill W Massey
This review examines evidence that serotonin (5-HT) agents reduce the effects of NMDA receptor antagonists (NMDA-RA) like PCP, MK-801, and ketamine on locomotor activity and novel object recognition (NOR) in rats—models used to study schizophrenia and antipsychotic drug action. Selective 5-HT(2A) inverse agonists and atypical antipsychotics (e.g., clozapine, lurasidone) are more effective than selective D(2) antagonists at attenuating NMDA-RA-induced hyperactivity. 5-HT(2A) inverse agonists alone do not improve NMDA-RA-impaired NOR but augment atypical antipsychotics' effects. 5-HT(1A) partial agonists and 5-HT(6)/5-HT(7) antagonists also attenuate these behaviors. 5-HT(2C) inverse agonists block NOR in naïve rats and interfere with atypical antipsychotics' restorative effects, highlighting constitutive 5-HT(2C) receptor activity's role.