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Behavioral effects of orally administered glycine in socially housed monkeys chronically treated with phencyclidine

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Abstract

Rationale

Schizophrenia is a major mental disorder. Dissociative anesthetics such as phencyclidine (PCP) produce a syndrome in humans that is clinically indistinguishable from schizophrenia by blocking neurotransmission at N-methyl-d-aspartate (NMDA)-type glutamate receptors. NMDA receptors in brain are modulated by the amino acid glycine (GLY), which reverses neurochemical and behavioral effects of PCP in rodents. The present study investigates GLY effects on PCP-induced behavior in primates.

Objectives

In primates, PCP induces characteristic behavioral symptoms that can be used to model positive and negative symptoms of schizophrenia. This study investigated the effects of GLY treatment in ten socially housed monkeys receiving chronically infused PCP.

Methods

Ten monkeys received escalating then stable doses of continuously infused PCP through a series of subcutaneously implanted osmotic minipumps. During a segment of the highest PCP dose period, monkeys were concurrently treated with glycine (2 g kg−1 day−1 bid p.o.). Behavioral observations were recorded during baseline and treatment periods.

Results

Chronic PCP treatment was associated with a progressive decrease in stereotyped pacing and a progressive increase in scanning behavior. Eight of ten animals had one or more episodes of extreme motoric and physiological responses precipitated by stressful events. GLY treatment significantly reversed the effects of PCP on stereotyped pacing but had no effect on scanning.

Conclusions

The results support GLY treatment as beneficial for negative symptoms of schizophrenia. Although further validation is needed, the results also indicate that chronic PCP in primates may be an appropriate model system for development of drugs targeting positive and negative symptoms of schizophrenia.

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Acknowledgments

We thank the NKI Clinical Chemistry Division for performing the serum PCP assays, Robert Lindsley for assistance with pump implant surgery, and Kai Lee for writing the behavioral data collection programs. This study was funded in part by grants R01 DA03383 and K02 MH01439 to DCJ. Conflict of interest: DCJ holds intellectual property rights for use of glycine in treatment of schizophrenia.

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  1. Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd, Orangeburg, NY, 10962, USA

    Gary S. Linn, Robert T. O’Keeffe, Kenneth Lifshitz, Charles Schroeder & Daniel C. Javitt

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  1. Gary S. Linn
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  2. Robert T. O’Keeffe
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  3. Kenneth Lifshitz
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  4. Charles Schroeder
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  5. Daniel C. Javitt
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Correspondence to Gary S. Linn.

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Linn, G.S., O’Keeffe, R.T., Lifshitz, K. et al. Behavioral effects of orally administered glycine in socially housed monkeys chronically treated with phencyclidine. Psychopharmacology 192, 27–38 (2007). https://doi.org/10.1007/s00213-007-0771-6

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