Amphetamine and D1 dopamine receptor agonists produce biphasic effects on glutamate efflux in rat ventral tegmental area: Modification by repeated amphetamine administration

Marina E. Wolf, Chang Jiang Xue

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Amphetamine or selective D1 and D2 dopamine receptor agonists and antagonists were administered to the ventral tegmental area (VTA) through a microdialysis probe to determine their effects on glutamate and aspartate efflux in rats pretreated for 5 days with vehicle or 5 mg/kg (+)-amphetamine sulfate. In vehicle rats, glutamate efflux declined during 2 h of perfusion with the D1 receptor agonist SKF-82958 (10 and 100 μM). After SKF-82958 perfusion ended, glutamate efflux rebounded to basal levels and continued to increase gradually over the next 2 h. A similar biphasic pattern was observed with intra-VTA amphetamine (10 and 100 μM) and with another D1 agonist (100 μM SKF-38393). The biphasic effects of SKF-82958 were prevented by coperfusion with a D1 antagonist (SCH-23390; 30 μM). Glutamate efflux was unaffected by a D2 agonist (100 μM quinpirole) and by D1 or D2 antagonists administered alone (SCH 23390 and eticlopride; 30 μM). In amphetamine- pretreated rats tested 2 days after the last injection, both the decrease during SKF-82958 perfusion and the delayed increase in glutamate efflux were attenuated. In rats tested 12-14 days after the last amphetamine injection, only the decrease during SKF-82958 perfusion was attenuated. None of these drug treatments produced consistent effects on aspartate efflux. We showed previously that systemic amphetamine (5 mg/kg, i.p.) has no immediate effect on VTA glutamate efflux but produces a delayed increase in glutamate efflux that reaches statistical significance 2-3 h after injection. Because behavioral sensitization can be elicited either by repeated systemic or repeated intra-VTA administration, neurochemical effects common to both routes (such as the delayed increase in glutamate efflux) are most likely to contribute to its induction.

Original languageEnglish (US)
Pages (from-to)198-209
Number of pages12
JournalJournal of neurochemistry
Volume70
Issue number1
DOIs
StatePublished - Jan 1998

Keywords

  • Amphetamine
  • D1 dopamine receptors
  • Glutamate
  • Microdialysis
  • Sensitization
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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