D-1 RECEPTORS MODULATE GLUTAMATE TRANSMISSION IN THE VENTRAL TEGMENTAL AREA

Perfusion of the D-1 agonist, SKF-82958, through a microdialysis probe implanted in the ventral tegmental area produced a dose-dependent increase in extracellular glutamate and GABA. The increase in extracellular glutamate occurred at approximately 30x lower dose than the elevation in GABA. The increase in extracellular glutamate by SKF-82958 was blocked by coperfusion of the D-1 antagonist, SCH-23390, and was not mimicked by perfusion of the D-2/3 agonist, quinpirole, into the ventral tegmental area. In contrast, the elevation in extracellular GABA was insensitive to blockade by SCH-23390. Systemic administration of cocaine (15 mg/kg, i.p.) produced a rapid elevation in extracellular glutamate lasting for 20 min that was prevented by pretreating the ventral tegmental area with SCH-23390. In contrast, acute cocaine produced a reduction in extracellular GABA content in the ventral tegmental area that was not affected by SCH-23390. These data indicate that the stimulation of D-1 receptors in the ventral tegmental area increases the release of glutamate and that increasing extracellular levels of somatodendritic dopamine by systemic cocaine can mimic this effect.