Ethanol increases glutamate neurotransmission in the posterior ventral tegmental area of female wistar rats.
BACKGROUND
The posterior ventral tegmental area (pVTA) mediates the reinforcing and stimulating effects of ethanol (EtOH). Electrophysiological studies indicated that exposure to EtOH increased glutamate synaptic function in the VTA. This study determined the neurochemical effects of both acute and repeated EtOH exposure on glutamate neurotransmission in the pVTA.


METHODS
Adult female Wistar rats were implanted with microdialysis probes in the pVTA. During microdialysis, rats received acute intraperitoneal (i.p.) injection of saline or EtOH (0.5, 1.0, or 2.0 g/kg), and extracellular glutamate levels were measured in the pVTA. The effects of repeated daily injections of EtOH (0.5, 1.0, or 2.0 g/kg) on basal extracellular glutamate concentrations in the pVTA and on glutamate response to a subsequent EtOH challenge were also examined.


RESULTS
The injection of 0.5 g/kg EtOH significantly increased (120 to 125% of baseline), whereas injection of 2.0 g/kg EtOH significantly decreased (80% of baseline) extracellular glutamate levels in the pVTA. The dose of 1.0 g/kg EtOH did not alter extracellular glutamate levels. Seven repeated daily injections of each dose of EtOH increased basal extracellular glutamate concentrations (from 4.1 ± 0.5 to 9.2 ± 0.5 μM) and reduced glutamate clearance in the pVTA (from 30 ± 2 to 17 ± 2%), but failed to alter glutamate response to a 2.0 g/kg EtOH challenge.


CONCLUSIONS
The results suggest that the low dose of EtOH can stimulate the release of glutamate in the pVTA, and repeated EtOH administration increased basal glutamate transmission in the pVTA, as a result of reduced glutamate clearance.
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, USA. zding@iupui.edu
Zheng-Ming
ZM
Ding
Eric A
EA
Engleman
Zachary A
ZA
Rodd
William J
WJ
McBride
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D007274:Injections, Intraperitoneal; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects*
D002492:Central Nervous System Depressants; D000431:Ethanol; D018698:Glutamic Acid