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Research ArticleArticle

Differences in Pharmacological Properties of Dopamine Release Between the Substantia Nigra and Striatum: An In Vivo Electrochemical Study

Alexander F. Hoffman and Greg A. Gerhardt
Journal of Pharmacology and Experimental Therapeutics April 1999, 289 (1) 455-463;
Alexander F. Hoffman
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Greg A. Gerhardt
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Abstract

The properties of dopamine (DA) release in the rat substantia nigra (SN) and striatum were investigated using high-speed chronoamperometric recordings in brain slices. In both brain regions, a 2-min bath superfusion with 30 mM KCl produced robust DA-like electrochemical signals, with the mean amplitude of the signal being >10-fold greater in the striatum than the SN. The reproducibility of the response was confirmed by a second stimulus (S2)/first-stimulus (S1) ratio of >0.8 in both regions. The bath application of tetrodotoxin significantly reduced the S2/S1 ratio in both the striatum and SN, implicating the requirement for voltage-sensitive sodium channels in the DA-release process. However, the application of cadmium chloride, a nonselective blocker of voltage-sensitive calcium channels, reduced the S2/S1 ratio only in the striatum and not within the SN. Moreover, removal of Ca2+ from the buffer did not significantly affect release within the SN, despite a >85% reduction in release within the striatum. In addition, although the D2 receptor antagonist sulpiride enhanced the S2/S1 ratio in the striatum, no effect of this agent was seen in the SN. Finally, the application ofd-amphetamine produced DA-like electrochemical signals in both the striatum and SN. However, the amplitude of thed-amphetamine-evoked response, relative to the KCl-evoked release, was much smaller in the striatum than in the SN. Taken together, these data support the hypothesis that differences in the mechanism or mechanisms of release exist between somatodendritic and axonal elements within the nigrostriatal pathway.

Footnotes

  • Send reprint requests to: Greg A. Gerhardt, Ph.D., Department of Psychiatry, Box C268–71, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262. E-mail:Greg.Gerhardt{at}UCHSC.edu

  • ↵1 This work was supported by Grants NS09(199) and AG06434. A.F.H. is a recipient of an Advanced Predoctoral Fellowship from the Pharmaceutical Researchers and Manufacturers of America Foundation, and G.A.G. received support from a Level II Research Scientist Development Award (MH01245) from the National Institute of Mental Health.

  • Abbreviations:
    DA
    dopamine
    SN
    substantia nigra
    SNc
    substantia nigra pars compacta
    SNr
    substantia nigra pars reticulata
    Tc
    clearance rate
    DAT
    dopamine transporter
    TTX
    tetrodotoxin
    aCSF
    artificial cerebrospinal fluid
    5-HT
    serotonin
    red/ox ratio
    reduction/oxidation ratio
    • Received August 12, 1998.
    • Accepted November 2, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 1
1 Apr 1999
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Research ArticleArticle

Differences in Pharmacological Properties of Dopamine Release Between the Substantia Nigra and Striatum: An In Vivo Electrochemical Study

Alexander F. Hoffman and Greg A. Gerhardt
Journal of Pharmacology and Experimental Therapeutics April 1, 1999, 289 (1) 455-463;

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Research ArticleArticle

Differences in Pharmacological Properties of Dopamine Release Between the Substantia Nigra and Striatum: An In Vivo Electrochemical Study

Alexander F. Hoffman and Greg A. Gerhardt
Journal of Pharmacology and Experimental Therapeutics April 1, 1999, 289 (1) 455-463;
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