Dopamine efflux from striatum after chronic nicotine

Evidence for autoreceptor desensitization

L. Hársing, Henry Sershen, Abel Lajtha

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

We examined the effect of chronic nicotine treatment on dopaminergic activity by measuring the effects of D1 and D2 dopamine (DA) receptor agonists and antagonists on tritium release from mouse striatum preloaded with [3H]DA. The radioactivity released during superfusion was separated on alumina columns and the distribution and efflux of [3H]DA and its main 3H-labeled metabolites were quantified. After preloading by incubation with [3H]DA, the electrical stimulation-evoked tritium overflow was higher in striatum prepared from nicotine-treated mice, whereas in vitro addition of nicotine caused a similar increase in tritium release from striatum of untreated and chronic nicotine-treated mice. The overflow Of [3H]DA and its 3H-metabolites exhibited similar distribution patterns in [3H]DA-preloaded striatum dissected from untreated and chronic nicotine-pretreated mice, indicating that repeated injections with nicotine did not alter the metabolism of [3H]DA taken up by the tissue. (-)-Quinpirole, a selective agonist for D2 DA receptors, and apomorphine, a nonselective D1/D2 agonist, inhibited the electrical stimulation-induced tritium efflux from striatum of untreated mice, whereas (±)-sulpiride, a D2 DA receptor antagonist, enhanced the evoked release of tritium. These changes in tritium efflux effected by (-)-quinpirole and (±)-sulpiride reflected changes in [3H]DA release and not in DA metabolism, as shown by separation of the released radioactivity on alumina columns. The D1 receptor agonist (±)-SKF-38393 did not affect the tritium overflow, whereas the D1 receptor antagonist (+)-SCH-23390 exerted a stimulatory action but only at a high concentration. In contrast, neither the DA receptor agonists [(-)-quinpirole, apomorphine, and (+)-SKF-38393] nor the antagonists [(±)-sulpiride and (+)-SCH-23390] altered the stimulation-evoked tritium release in striatum obtained from mice repeatedly treated with nicotine. It is concluded that chronic administration of nicotine produces an increased release of DA in the striatum with a resulting elevation of synaptic DA concentrations leading to development of D2 DA autoreceptor subsensitivity. As a consequence, chronic nicotine may attenuate autoinhibition of dopaminergic neurotransmission in the striatum.

Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalJournal of Neurochemistry
Volume59
Issue number1
Publication statusPublished - Jul 1992

Fingerprint

Autoreceptors
Nicotine
Tritium
Dopamine
Quinpirole
Sulpiride
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Aluminum Oxide
Apomorphine
Dopamine Agonists
Radioactivity
Metabolites
Metabolism
Electric Stimulation
Dopamine Antagonists
Dopamine D2 Receptors
Synaptic Transmission

Keywords

  • [H]dopamine release
  • D and D agonists
  • D and D antagonists
  • Nicotine
  • Striatum

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Dopamine efflux from striatum after chronic nicotine : Evidence for autoreceptor desensitization. / Hársing, L.; Sershen, Henry; Lajtha, Abel.

In: Journal of Neurochemistry, Vol. 59, No. 1, 07.1992, p. 48-54.

Research output: Contribution to journalArticle

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N2 - We examined the effect of chronic nicotine treatment on dopaminergic activity by measuring the effects of D1 and D2 dopamine (DA) receptor agonists and antagonists on tritium release from mouse striatum preloaded with [3H]DA. The radioactivity released during superfusion was separated on alumina columns and the distribution and efflux of [3H]DA and its main 3H-labeled metabolites were quantified. After preloading by incubation with [3H]DA, the electrical stimulation-evoked tritium overflow was higher in striatum prepared from nicotine-treated mice, whereas in vitro addition of nicotine caused a similar increase in tritium release from striatum of untreated and chronic nicotine-treated mice. The overflow Of [3H]DA and its 3H-metabolites exhibited similar distribution patterns in [3H]DA-preloaded striatum dissected from untreated and chronic nicotine-pretreated mice, indicating that repeated injections with nicotine did not alter the metabolism of [3H]DA taken up by the tissue. (-)-Quinpirole, a selective agonist for D2 DA receptors, and apomorphine, a nonselective D1/D2 agonist, inhibited the electrical stimulation-induced tritium efflux from striatum of untreated mice, whereas (±)-sulpiride, a D2 DA receptor antagonist, enhanced the evoked release of tritium. These changes in tritium efflux effected by (-)-quinpirole and (±)-sulpiride reflected changes in [3H]DA release and not in DA metabolism, as shown by separation of the released radioactivity on alumina columns. The D1 receptor agonist (±)-SKF-38393 did not affect the tritium overflow, whereas the D1 receptor antagonist (+)-SCH-23390 exerted a stimulatory action but only at a high concentration. In contrast, neither the DA receptor agonists [(-)-quinpirole, apomorphine, and (+)-SKF-38393] nor the antagonists [(±)-sulpiride and (+)-SCH-23390] altered the stimulation-evoked tritium release in striatum obtained from mice repeatedly treated with nicotine. It is concluded that chronic administration of nicotine produces an increased release of DA in the striatum with a resulting elevation of synaptic DA concentrations leading to development of D2 DA autoreceptor subsensitivity. As a consequence, chronic nicotine may attenuate autoinhibition of dopaminergic neurotransmission in the striatum.

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