Dopamine-, NMDA- and sigma-receptor antagonists exert differential effects on basal and amphetamine-induced changes in neostriatal ascorbate and DOPAC in awake, behaving rats

R. Christopher Pierce, George V. Rebec

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Amphetamine and other dopamine agonists elevate the extracellular level of neostriatal ascorbate, which has been shown to modulate neuronal function. To assess the receptor mechanisms underlying neostriatal ascorbate release, drug-induced changes in both basal and amphetamine-induced ascorbate release were monitored voltammetrically in the neostriatum of freely moving rats. A variety of dopamine receptor antagonists decreased basal ascorbate and reversed the increase induced by 2.5 mg/kg d-amphetamine. Thus, compared to vehicle treatment, administration of classical (haloperidol) and atypical (clozapine) neuroleptics or selective D1 (SCH-23390) and D2 (sulpiride) antagonists completely reversed the amphetamine-induced rise in ascorbate and also lowered basal levels by 20-40%. These same effects occurred following injection of dizocilpine (MK-801), a non-competitive NMDA antagonist, whereas BMY-14802, a sigma ligand, reversed the amphetamine-induced rise without altering basal levels. Simultaneous measurements of extracellular DOPAC, a major dopamine metabolite, revealed that haloperidol, clozapine, sulpride and BMY-14802 elevated basal levels and reversed the amphetamine-induced decline. Dizocilpine also increased basal DOPAC but failed to alter DOPAC response to amphetamine, whereas both basal and amphetamine-induced changes in DOPAC were unaffected by SCH-23390. A combination of subthreshold doses of SCH-23390 and sulpride, however, reversed both the amphetamine-induced release of ascorbate and the correponding decline DOPAC. Collectively, these results suggest that whereas dopamine, sigma, and NMDA receptors modulate neostriatal ascorbate release, they exert an opposing influence on extracellular DOPAC. All drugs attenuated at least some components of the amphetamine behavioral response, suggesting a role for multiple mechanisms in the behavioral effects of this drug.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalBrain research
Volume579
Issue number1
DOIs
StatePublished - May 1 1992
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint

Dive into the research topics of 'Dopamine-, NMDA- and sigma-receptor antagonists exert differential effects on basal and amphetamine-induced changes in neostriatal ascorbate and DOPAC in awake, behaving rats'. Together they form a unique fingerprint.

Cite this