Phencyclidine

Correlation of brain levels with behavioral effects and absence of a dispositional component to the observed tolerance

Thomas F. Murray, A. Horita

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Abstract

Using schedule-controlled behavior in rats, we have reported (Life Sci. 22, 195, 1978) complete tolerance development to the phencyclidine (PCP)-induced rate depressant effect after 7 daily treatments of 4 mg/kg. A method was developed for the measurement of [3H]-PCP and metabolites in the brain and blood of male Sprague-Dawley rats. The assay method involved sample extraction and thin-layer chromatographic separation with nonlabeled standards of PCP, 4-phenyl-4-piperidinocyclohexanol, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine to obtain Rf reference values for the identification of the compounds in the extracts. Animals received 6 daily treatments of 0.9% saline or 4 mg/kg PCP i.p. prior to administration of 4 mg/kg [3H]-PCP (96 μCi/kg i.p.) on day 7. The peak brain levels of [3H]-PCP were detected at 15 minutes after i.p. injection in both groups, and the concentrations of the parent compound and metabolites in the acute and subacute animals were not significantly different. These data argue against a dispositional mechanism of tolerance for this particular subacute dosing regimen. The time of maximum brain levels of PCP after the 4 mg/kg i.p. dose is in excellent correlation with the peak behavioral effects for both schedule-controlled behavior and the PCP-induced stereotyped behavioral syndrome.

Original languageEnglish
JournalFederation Proceedings
Volume38
Issue number3 I
StatePublished - 1979
Externally publishedYes

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Phencyclidine
Appointments and Schedules
Brain
Sprague Dawley Rats
Reference Values
Injections
Therapeutics

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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title = "Phencyclidine: Correlation of brain levels with behavioral effects and absence of a dispositional component to the observed tolerance",
abstract = "Using schedule-controlled behavior in rats, we have reported (Life Sci. 22, 195, 1978) complete tolerance development to the phencyclidine (PCP)-induced rate depressant effect after 7 daily treatments of 4 mg/kg. A method was developed for the measurement of [3H]-PCP and metabolites in the brain and blood of male Sprague-Dawley rats. The assay method involved sample extraction and thin-layer chromatographic separation with nonlabeled standards of PCP, 4-phenyl-4-piperidinocyclohexanol, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine to obtain Rf reference values for the identification of the compounds in the extracts. Animals received 6 daily treatments of 0.9{\%} saline or 4 mg/kg PCP i.p. prior to administration of 4 mg/kg [3H]-PCP (96 μCi/kg i.p.) on day 7. The peak brain levels of [3H]-PCP were detected at 15 minutes after i.p. injection in both groups, and the concentrations of the parent compound and metabolites in the acute and subacute animals were not significantly different. These data argue against a dispositional mechanism of tolerance for this particular subacute dosing regimen. The time of maximum brain levels of PCP after the 4 mg/kg i.p. dose is in excellent correlation with the peak behavioral effects for both schedule-controlled behavior and the PCP-induced stereotyped behavioral syndrome.",
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TY - JOUR

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T2 - Correlation of brain levels with behavioral effects and absence of a dispositional component to the observed tolerance

AU - Murray, Thomas F.

AU - Horita, A.

PY - 1979

Y1 - 1979

N2 - Using schedule-controlled behavior in rats, we have reported (Life Sci. 22, 195, 1978) complete tolerance development to the phencyclidine (PCP)-induced rate depressant effect after 7 daily treatments of 4 mg/kg. A method was developed for the measurement of [3H]-PCP and metabolites in the brain and blood of male Sprague-Dawley rats. The assay method involved sample extraction and thin-layer chromatographic separation with nonlabeled standards of PCP, 4-phenyl-4-piperidinocyclohexanol, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine to obtain Rf reference values for the identification of the compounds in the extracts. Animals received 6 daily treatments of 0.9% saline or 4 mg/kg PCP i.p. prior to administration of 4 mg/kg [3H]-PCP (96 μCi/kg i.p.) on day 7. The peak brain levels of [3H]-PCP were detected at 15 minutes after i.p. injection in both groups, and the concentrations of the parent compound and metabolites in the acute and subacute animals were not significantly different. These data argue against a dispositional mechanism of tolerance for this particular subacute dosing regimen. The time of maximum brain levels of PCP after the 4 mg/kg i.p. dose is in excellent correlation with the peak behavioral effects for both schedule-controlled behavior and the PCP-induced stereotyped behavioral syndrome.

AB - Using schedule-controlled behavior in rats, we have reported (Life Sci. 22, 195, 1978) complete tolerance development to the phencyclidine (PCP)-induced rate depressant effect after 7 daily treatments of 4 mg/kg. A method was developed for the measurement of [3H]-PCP and metabolites in the brain and blood of male Sprague-Dawley rats. The assay method involved sample extraction and thin-layer chromatographic separation with nonlabeled standards of PCP, 4-phenyl-4-piperidinocyclohexanol, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine to obtain Rf reference values for the identification of the compounds in the extracts. Animals received 6 daily treatments of 0.9% saline or 4 mg/kg PCP i.p. prior to administration of 4 mg/kg [3H]-PCP (96 μCi/kg i.p.) on day 7. The peak brain levels of [3H]-PCP were detected at 15 minutes after i.p. injection in both groups, and the concentrations of the parent compound and metabolites in the acute and subacute animals were not significantly different. These data argue against a dispositional mechanism of tolerance for this particular subacute dosing regimen. The time of maximum brain levels of PCP after the 4 mg/kg i.p. dose is in excellent correlation with the peak behavioral effects for both schedule-controlled behavior and the PCP-induced stereotyped behavioral syndrome.

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