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Annotation

Homayoun H, Moghaddam B. Fine-tuning of awake prefrontal cortex neurons by clozapine: comparison with haloperidol and N-desmethylclozapine. Biol Psychiatry . 2007 Mar 1 ; 61(5):679-87. PubMed Abstract

Comments on Paper and Primary News
Primary News: Order in the Cortex: Clozapine Curbs Unruly Networks

Comment by:  J David Jentsch
Submitted 16 September 2007 Posted 17 September 2007

The article by Kargieman and colleagues further specifies the cellular mechanisms underlying the actions of clozapine in a model of pharmacologically induced cortical dysfunction. Separately, clozapine has been demonstrated to be capable of reducing or eliminating the complex behavioral and cognitive impairments elicited by acutely administered NMDA antagonists (Geyer et al., 2001; Idris et al., 2005; Lipina et al., 2005), and these cellular mechanisms shown by Kargieman et al. may represent the level of interaction between clozapine and phencyclidine-like drugs.

What is surprising from so many of these studies is the quality of the reversal of effects produced by clozapine, despite the fact that it (like most other antipsychotic drugs) has limited efficacy both at an individual and population level. Furthermore, there remain many reports in the literature demonstrating that while some cognitive and symptomatic domains in schizophrenia...  Read more


View all comments by J David Jentsch

Primary News: Order in the Cortex: Clozapine Curbs Unruly Networks

Comment by:  Jeremy Seamans
Submitted 28 September 2007 Posted 28 September 2007

The paper by Kargieman et al. provides an interesting perspective on the effects of PCP on activity in the prefrontal cortex. Dr. Javitt brings up an excellent point in his commentary that the study highlights the importance of PCP in this preparation as a model of slow-wave sleep disturbances in schizophrenia. In anesthetized animals, field potential recordings resemble the up and down states observed in slow-wave sleep. These states are driven by NMDA receptors and, accordingly, NMDA antagonists such as PCP and ketamine should reduce them as reported. The odd thing about NMDA antagonists is that they themselves can be used as anesthetics to produce a state where slow delta oscillations predominate. For instance, robust up and down states or slow oscillations at or below delta are observed when ketamine is used as an anesthetic. Therefore, NMDA antagonists can induce a state where delta activity is prominent, yet if the subject is already in that state, the effect of the drug is to reduce such activity.

So this also may be the case with PCP. There are numerous EEG studies...  Read more


View all comments by Jeremy Seamans
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