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OtherNEUROPHARMACOLOGY

Pharmacological Comparison of Transient and Persistent [3H]Dopamine Release from Mouse Striatal Synaptosomes and Response to Chronic l-Nicotine Treatment

Sharon R. Grady, Elizabeth U. Grun, Michael J. Marks and Allan C. Collins
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 32-43;
Sharon R. Grady
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Elizabeth U. Grun
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Michael J. Marks
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Allan C. Collins
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Abstract

l-Nicotine stimulates a biphasic release of [3H]dopamine from mouse striatal synaptosomes which does not persist after agonist is removed. Approximately 80% of the initial release is transient and disappears with a half-time of less than 1 min; the other 20% persists for several minutes (t 1/2, 5–10 min). Both the transient and persistent phases were investigated by 10-min exposures to agonists with an in vitro perfusion technique. A series of nicotinic agonists and antagonists were used to determine the pharmacological relationship of the two phases. Parameters measured included EC50 and V max values and desensitization rates for both phases for agonists,K i values for antagonists andK i values for low concentrations of agonists. The results are consistent with both phases being mediated by a single type of receptor. In addition, the effects of chronic nicotine treatment on transient and persistent [3H]DA release were measured. For both phases, release was decreased approximately 15% by chronic infusion of 4.0 mg/kg/hr l-nicotine. Correlation of the results with inactivation of a portion of the receptors rather than a reversible desensitization is discussed.

Footnotes

  • Send reprint requests to: Allan C. Collins, IBG Campus Box 447, University of Colorado, Boulder, CO 80309.

  • ↵1 This work was supported by grants DA-03194 and DA-00197 from the National Institute on Drug Abuse.

  • Abbreviations:
    ACh
    acetylcholine
    ATR
    atropine
    ATX
    anatoxin-a
    CARB
    carbachol
    CYT
    cytisine
    DA
    dopamine
    DEC
    decamethonium
    DFP
    diisopropyl fluorophosphate
    DHβE
    dihydro-β-erythroidine
    EPI
    (+)-epibatidine
    HEPES
    N-[2-hydroxyethyl]-piperazine-N′-[2-ethanesulfonate]
    HEX
    hexamethonium
    MEC
    mecamylamine
    MeCARB
    methylcarbachol
    MLA
    methyllycaconitine
    nAChR
    neuronal nicotinic acetylcholine receptor
    nBTX
    neuronal bungarotoxin
    NIC
    nicotine
    dTC
    d-tubocurarine
    TMA
    tetramethylammonium
    • Received September 30, 1996.
    • Accepted March 6, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
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OtherNEUROPHARMACOLOGY

Pharmacological Comparison of Transient and Persistent [3H]Dopamine Release from Mouse Striatal Synaptosomes and Response to Chronic l-Nicotine Treatment

Sharon R. Grady, Elizabeth U. Grun, Michael J. Marks and Allan C. Collins
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 32-43;

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Pharmacological Comparison of Transient and Persistent [3H]Dopamine Release from Mouse Striatal Synaptosomes and Response to Chronic l-Nicotine Treatment

Sharon R. Grady, Elizabeth U. Grun, Michael J. Marks and Allan C. Collins
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 32-43;
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