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

J Neurochem. 1998 Jan;70(1):198-209. doi: 10.1046/j.1471-4159.1998.70010198.x.


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 microM). 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 microM) and with another D1 agonist (100 microM SKF-38393). The biphasic effects of SKF-82958 were prevented by coperfusion with a D1 antagonist (SCH-23390; 30 microM). Glutamate efflux was unaffected by a D2 agonist (100 microM quinpirole) and by D1 or D2 antagonists administered alone (SCH 23390 and eticlopride; 30 microM). 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Amphetamine / administration & dosage
  • Amphetamine / pharmacology*
  • Animals
  • Benzazepines / pharmacology
  • Glutamic Acid / metabolism*
  • Male
  • Microdialysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / agonists*
  • Time Factors
  • Ventral Tegmental Area / metabolism*


  • Benzazepines
  • Receptors, Dopamine D1
  • Glutamic Acid
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • SK&F 82958
  • Amphetamine