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MPTP lesions of the nigrostriatal dopaminergic projection decrease [3H]1-[1-(2-thienyl)cyclohexyl]-piperidine binding to PCP site 2: Further evidence that PCP site 2 is associated with the biogenic amine reuptake complex

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Abstract

Our previous studies have demonstrated that, using membranes of guinea pig brain, [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) labels not only the phencyclidine binding site associated with the NMDA receptor (PCP site 1), but also a second high affinity binding site which is associated with the biogenic amine reuptake carrier (termed PCP site 2). To test this hypothesis, the binding of [3H]GBR12935 to the dopamine transporter, and [3H]TCP binding to PCP sites 1 and 2 were measured in caudates harvested from control MPTP-treated and reserpine-treated dogs. MPTP treatment decreased dopamine levels by over 99%, decreased [3H]GBR12935 binding by over 90%, decreased [3H]TCP binding to PCP site 2 by about 50%, and had no significant effect on [3H]TCP binding to PCP site 1. These data are consistent with hypothesis that a portion of PCP site 2 is associated with dopaminergic nerve, terminals in dog caudate.

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Authors and Affiliations

  1. Laboratory of Medicinal Chemistry, NIDDK, Bldg. 10-3D41, 20892, Bethesda, MD

    Hyacinth C. Akunne, Brian R. de Costa & Kenner C. Rice

  2. Laboratory of Clinical Science, NIMH, 20892, Bethesda, MD

    Jan N. Johannessen

  3. Division of Toxicology, Center for Food Safety and Applied Nutrition, FDA, 20204, Washington, D.C.

    Jan N. Johannessen

  4. Laboratory of Clinical Psychopharmacology, NIDA Addiction Research Center, PO BOX 5180, 21224, Baltimore, MD

    Richard B. Rothman

Authors
  1. Hyacinth C. Akunne
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  2. Jan N. Johannessen
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  3. Brian R. de Costa
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  4. Kenner C. Rice
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  5. Richard B. Rothman
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Akunne, H.C., Johannessen, J.N., de Costa, B.R. et al. MPTP lesions of the nigrostriatal dopaminergic projection decrease [3H]1-[1-(2-thienyl)cyclohexyl]-piperidine binding to PCP site 2: Further evidence that PCP site 2 is associated with the biogenic amine reuptake complex. Neurochem Res 17, 261–264 (1992). https://doi.org/10.1007/BF00966668

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  • DOI: https://doi.org/10.1007/BF00966668

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