Jan 8, 2011

The role of serotonin in the NMDA receptor antagonist models of psychosis and cognitive impairment

Herbert Y MeltzerB W Massey


To review the evidence that agents which preferentially affect serotonin (5-HT) attenuate the ability of N-methyl-D-aspartate (NMDA) receptor non-competitive antagonists (NMDA-RA), e.g., phencyclidine (PCP), dizocilpine (MK-801), and ketamine, to stimulate locomotor activity (LA), and to impair novel object recognition (NOR). NMDA-RA-induced increased LA and impairment of NOR are widely used models of the pathophysiology of schizophrenia, the mechanism of action of antipsychotic drugs (APDs), and the identification of novel treatments. Serotonin (5-HT) plays an important role in attenuating these effects of NMDA-RA. Selective 5-HT(2A) inverse agonists, e.g., M100907 and ACP-103, and atypical APDs, which are more potent 5-HT(2A) than D(2) antagonists, e.g., clozapine and lurasidone, are more effective than selective D(2) receptor antagonists to attenuate NMDA-RA-induced increased LA. 5-HT(2A) inverse agonists alone are not effective to improve NMDA-RA-impaired NOR, but augment the effects of atypical, but not typical APDs, to improve NOR. The 5-HT(1A) receptor partial agonist tandospirone alone and the 5-HT(1A) agonist effects of atypical APDs may substitute for, or contribute to, the effects of D(2) and 5-HT(2A) receptor antago...Continue Reading

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Mentioned in this Paper

Antipsychotic Effect
Receptor, Serotonin,5-HT2A
Serotonin Measurement
ACP 103
Receptors, Tryptamine
Receptor, Serotonin,5-HT1A

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