Excitatory amino acid receptor-mediated responses in periaqueductal gray neurons are increased during ethanol withdrawal.
The ventrolateral periaqueductal gray (PAG) is critical for propagation in the neuronal network for ethanol withdrawal (ETX) seizures, and ethanol is known to alter glutamate effects. This study evaluated changes in glutamate antagonist effects on PAG neurophysiology in brain slices from rats treated with ethanol in vivo. Spontaneous action potentials were rare in control PAG neurons but common during ETX. Spontaneous excitatory postsynaptic potential (EPSP) frequency was increased during ETX, and an AMPA antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) was more effective in suppressing this activity than an NMDA antagonist, 2-amino-7-phosphonoheptanoate (AP7). EPSPs evoked by stimulation of dorsolateral PAG were decreased by AP7 or DNQX in ETX and control neurons. EPSPs of ETX neurons were significantly less sensitive than controls to blockade by AP7 and DNQX. Paired-pulse facilitation of EPSPs was significantly increased during ETX, but paired-pulse inhibition occurred in controls. Thus, PAG hyperexcitability during ETX results from alterations of both NMDA and AMPA receptor-mediated neurotransmission, which may contribute importantly to ETX seizures. These results differ from previous findings in the seizure-initiating site for ETX seizures, inferior colliculus (IC), where NMDA receptor-mediated mechanisms dominate excitability increases during ETX. This dichotomy may be related to the different role played by IC and PAG in the ETX seizure network.
Long
Cheng
C
Department of Pharmacology, Southern Illinois University School of Medicine, PO Box 19629, Springfield, IL 62794-9629, USA.
Yang
Li
L
Faingold
Carl L
CL
Steven Evans
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010487:Periaqueductal Gray / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000473:pathology* / Q000503:physiopathology
D002492:Central Nervous System Depressants; D018683:Excitatory Amino Acid Agents; D017470:Receptors, Glutamate; D000431:Ethanol