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3[H]-Sulpiride labels mesolimbic non-dopaminergic sites that bind antidepressant drugs

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Summary

3[H]-(−)-Sulpiride and 3[H]-spiperone binding was compared in rat amygdala, nucleus accumbens and striatum, using (+/−)-sulpiride to define specific binding. 3[H]-(−)-Sulpiride bound to twice as many sites in amygdala and nucleus accumbens as 3[H]-spiperone. 3[H]-(−)-Sulpiride binding was directed to these additional sites by using 1 μM spiperone to mask dopaminergic binding. The binding of 3[H]-(−)-sulpiride to these sites was high affinity, reversible, Na+-dependent, but not stereospecific. Metoclopramide, tiapride and antidepressant medications, but not other neuroleptics, ADTN, or serotonin displaced 3[H]-(−)-sulpiride binding to these sites. These data suggest that 3[H]-(−)-sulpiride labels mesolimbic sites other than dopamine receptors which may mediate antidepressant effects.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3801 Miranda Avenue, 94304, Palo Alto, California, USA

    J. G. Csernansky, C. A. Csernansky & L. E. Hollister

  2. Palo Alto VA Medical Center, 3801 Miranda Avenue, 94304, Palo Alto, California, USA

    J. G. Csernansky, C. A. Csernansky & L. E. Hollister

Authors
  1. J. G. Csernansky
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  2. C. A. Csernansky
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  3. L. E. Hollister
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Additional information

We wish to acknowledge the help of Dr Roland Ciaranello, who suggested that tricyclic antidepressants might displace the additional 3[H]-(−)-sulpiride binding, and Drs Mark Hambin and Philip Seeman, who reviewed the manuscript. We thank the following pharmaceutical companies for providing drug reagents: (±)-sulpiride — Delagrange; (+)-(−)-sulpiride — Ravizza; diazepam — Roche; alprazolam — Upjohn; imipramine — Ciba; Desipramine — USV Pharmaceutical; amitriptyline — Merck, Sharp and Dohme; nortriptyline-Lilly; cinnanserin and fluphenazine — Squibb; cis-thiothixene — Pfizer; thioridazine — Sandoz; cis- and trans-flupenthixol — H. Lundbeck; chlorpromazine — Smith, Kline and French; spiroperidol — Janssen; metoclopramide — A.H. Robbins; and tiapride — Essex Pharma A/S. This work was supported by NIMH grant MH-03030 (LEH), by a VA Research Associate Award to JGC, and by the Research Service of the Veterans Administration.

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Csernansky, J.G., Csernansky, C.A. & Hollister, L.E. 3[H]-Sulpiride labels mesolimbic non-dopaminergic sites that bind antidepressant drugs. Experientia 41, 1419–1421 (1985). https://doi.org/10.1007/BF01950013

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  • DOI: https://doi.org/10.1007/BF01950013

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