Featured Review Cellscience Reviews Vol.2 No.4 ISSN 1742-8130

Wired for psychosis - psychopharmacology and circuitry underlying
the actions of angel dust (PCP) and ketamine

Abstract

Phencyclidine (PCP, angel dust), Ketamine (Special K) and other non-competitive NMDA receptor antagonists cause psychosis in humans. PCP and Special K also injure neurons in limbic cortex of adult rodents by blocking NMDA receptors on GABA neurons in the thalamus. Typical and atypical neuroleptics decrease psychosis in humans and block the injury in rodent limbic cortex produced by PCP and Special K. This review proposes brain circuits that account for these observations, and suggest that antipsychotic medications work by enhancing GABA neuronal activity in the thalamus and cortex to decrease the activation of circuits that mediate psychosis.

Psychosis is a common psychiatric symptom that occurs in association with many conditions including schizophrenia, depression and certain drugs of abuse including PCP (Phencyclidine, angel dust) and ketamine (Special K) [1]. PCP, ketamine, MK-801, dextromethorphan and related drugs are non-competitive antagonists of the glutamate NMDA receptor channel. The psychosis produced by PCP and ketamine has positive and negative symptoms that have been said to best mimic the psychosis seen in patients with psychosis due to schizophrenia [2-14]. Low doses of both drugs precipitate psychosis in schizophrenics [9]. These observations have led to combined hyper-dopaminergic, hypo-NMDA glutamate receptor theories of schizophrenia [15-20]. These ideas have led to successful treatment trials with dopamine receptor antagonists and NMDA-receptor/ glutamate agonists for the treatment of psychosis [15, 16, 21-27].

Please click to access complete issue ($4.95) and to download full article in or formats