D1 receptors modulate glutamate transmission in the ventral tegmental area.
Perfusion of the D1 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 D1 antagonist, SCH-23390, and was not mimicked by perfusion of the D2/3 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 D1 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.
Kalivas
P W
PW
Alcohol and Drug Abuse Program, Washington State University, Pullman 99164-6520, USA.
Duffy
P
P
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C071262:SK&F 82958; D003042:Cocaine