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Research ArticleArticle

R(+)-8-OH-DPAT, a Serotonin1A Receptor Agonist, Potentiated S(−)-Sulpiride-Induced Dopamine Release in Rat Medial Prefrontal Cortex and Nucleus Accumbens But Not Striatum

Junji Ichikawa and Herbert Y. Meltzer
Journal of Pharmacology and Experimental Therapeutics December 1999, 291 (3) 1227-1232;
Junji Ichikawa
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Herbert Y. Meltzer
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Abstract

The serotonin (5-HT)2A/2C receptor antagonist ritanserin has been reported to potentiate the dopamine (DA) D2/3receptor antagonist raclopride-induced DA release in medial prefrontal cortex (mPFC) and nucleus accumbens (NAC) but not striatum (STR). Because of reciprocal interactions between 5-HT2A and 5-HT1A receptors, we tested the hypothesis that 5-HT1A receptor agonism also potentiates D2/3 receptor antagonist-induced DA release using a combination of the 5-HT1A receptor agonistR(+)-8-hydroxy-2-(di-n-propylamino)-tetralin [R(+)-8-OH-DPAT] and the D2/3 receptor antagonist S(−)-sulpiride (SUL).R(+)-8-OH-DPAT (0.05 mg/kg s.c.) potentiated low but not high dose SUL (1, 3 but not 10 or 25 mg/kg s.c.)-induced DA release in NAC, but had no effect in STR at all doses tested (1, 3, 10, and 25 mg/kg s.c.). However, R(+)-8-OH-DPAT (0.05 mg/kg s.c.) alone had no effect on basal, potentiated SUL (10 and 25 mg/kg s.c.)-induced DA release in mPFC; the effect of low dose SUL (1 and 3 mg/kg s.c.) was not tested because it alone had no effect on DA release. This potentiation was abolished by pretreatment with the 5-HT1A receptor antagonist WAY100635 (0.05 mg/kg s.c.), which alone had no effect on DA release. These results suggest that 5-HT1A receptor agonism facilitates DA release in mPFC and NAC but not STR in combination with D2 receptor antagonism.

Footnotes

  • Send reprint requests to: Junji Ichikawa, M.D., Ph.D., 1601 23rd Avenue South, Suite 306, The Psychiatric Hospital at Vanderbilt, Nashville, TN 37212. E-mail: ichikaj{at}ctrvax.vanderbilt.edu

  • ↵1 This work was supported in part by U.S. Public Health Services Grant MH41684. Preliminary data from this study have been reported in abstract form at the annual meeting of the Society for Neuroscience, 1997.

  • Abbreviations:
    5-HT
    5-hydroxytryptamine
    DA
    dopamine
    STR
    striatum
    NAC
    nucleus accumbens
    mPFC
    medial prefrontal cortex
    DRN
    dorsal raphe nucleus
    8-OH-DPAT
    8-hydroxy-2-(di-n-propylamino)-tetralin
    WAY100635
    n-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-n-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride
    SNC
    substantia nigra zona compacta
    VTA
    ventral tegmental area
    EPS
    extrapyramidal symptoms
    SUL
    S(−)-sulpiride
    • Received March 30, 1999.
    • Accepted August 30, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 3
1 Dec 1999
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Research ArticleArticle

R(+)-8-OH-DPAT, a Serotonin1A Receptor Agonist, Potentiated S(−)-Sulpiride-Induced Dopamine Release in Rat Medial Prefrontal Cortex and Nucleus Accumbens But Not Striatum

Junji Ichikawa and Herbert Y. Meltzer
Journal of Pharmacology and Experimental Therapeutics December 1, 1999, 291 (3) 1227-1232;

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Research ArticleArticle

R(+)-8-OH-DPAT, a Serotonin1A Receptor Agonist, Potentiated S(−)-Sulpiride-Induced Dopamine Release in Rat Medial Prefrontal Cortex and Nucleus Accumbens But Not Striatum

Junji Ichikawa and Herbert Y. Meltzer
Journal of Pharmacology and Experimental Therapeutics December 1, 1999, 291 (3) 1227-1232;
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