Phencyclidine-induced alterations of rat electrophysiology

Snyder, Edward W.; Schlehuber, C; Dustman, Robert E.; Shearer, Donald E.

doi:10.1016/0361-9230(81)90015-0

Cited by 15 publications

(1 citation statement)

References 16 publications

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“…Indeed, phencyclidine (PCP), a non-competitive antagonist at the NMDA receptor, is an anesthetic agent that has dissociative and psychotomimetic properties in man (Javitt and Zukin 1991). PCP produces a state of sensory isolation, seeming “drunkenness” and hallucinations, often followed by a feeling of depersonalization in abusers (Snyder et al 1981), and schizophrenic-like symptoms in healthy volunteers (Jentsch and Roth 1999; Luby et al 1959). Psychotic symptoms induced by PCP, or the pharmacologically related compound ketamine, include both positive (hallucinations, delusions) and negative (formal thought disorder, social withdrawal) symptoms, as well as cognitive dysfunction (Cosgrove and Newell 1991).…”

Section: Resultsmentioning

confidence: 99%

Direct and indirect interactions of the dopamine D3 receptor with glutamate pathways: implications for the treatment of schizophrenia

Sokoloff

Leriche

Díaz

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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This article, based on original data as well as on previously reported preclinical and clinical data that are reviewed, describes direct and indirect interactions of the D3 receptor with N-methyl-d-aspartate receptor (NMDA) signaling and their functional consequences and therapeutic implications for schizophrenia. D3 receptor immunoreactivity at ultrastructural level with electron microscopy was identified at presumably glutamatergic, asymmetric synapses of the medium-sized spiny neurons of the nucleus accumbens. This finding supports the existence of a direct interaction of the D3 receptor with glutamate, in line with previously described interactions with NMDA signaling involving Ca2+/calmodulin-dependent protein kinase II at post-synaptic densities (Liu et al. 2009). Indirect interactions of the D3 receptor with glutamate could involve a negative control exerted by the D3 receptor on mesocortical dopamine neurons and the complex regulation of the glutamatergic pyramidal cells by dopamine in the prefrontal cortex. This could be exemplified here by the regulation of pyramidal cell activity in conditions of chronic NMDA receptor blockade with dizocilpine (MK-801). BP897, a D3 receptor-selective partial agonist, reversed the dysregulation of cortical c-fos mRNA expression and pyramidal cell hyperexcitability, as measured by paired-pulse electrophysiology. At the behavioral level, blockade of the D3 receptor, by known D3 receptor antagonists or the novel D3 receptor-selective antagonist F17141, produces antipsychotic-like effects in reversing hyperactivity and social interaction deficits induced by NMDA receptor blockade by MK-801 in mice. The glutamate–D3 receptor interactions described here offer a conceptual framework for developing new D3 receptor-selective drugs, which may appear as an original, efficacious, and safe way to potentially indirectly target glutamate in schizophrenia.

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Section: Resultsmentioning

confidence: 99%

Direct and indirect interactions of the dopamine D3 receptor with glutamate pathways: implications for the treatment of schizophrenia

Sokoloff

Leriche

Díaz

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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Effect of phencyclidine on inhibition in the hippocampal slice

Bourne

Théôret

Esplin

et al. 1983

Naunyn-Schmiedeberg's Arch. Pharmacol.

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The effects of phencyclidine (PCP) on synaptic transmission were studied in the hippocampal slice. Population spikes evoked by orthodromic or antidromic stimulation were recorded from CAl pyramidal cells. Bath applied PCP (10(-4) M) reduced moderately both the orthodromic and antidromic population spikes. Lower concentrations, 5 X 10(-6) to 5 X 10(-5) M of PCP, which did not depress the population spikes, reduced inhibition of the orthodromically evoked spike in a dose dependent reversible manner. Diazepam (10(-6) to 10(-5) M) restored the inhibition despite the continued presence of PCP. It is suggested that PCP-induced seizures and other signs of hyperexcitability could be a result of reduced inhibition.

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