Ethanol inhibits persistent activity in prefrontal cortical neurons.
Cognitive functions supported by neurons in the prefrontal cortex (PFC) are disrupted by acute and chronic exposure to alcohol, yet little is known about the mechanisms that underlie these effects. In the present study, in vivo and in vitro electrophysiology was used to determine the effects of ethanol on neuronal firing and network patterns of persistent activity in PFC neurons. In vivo, ethanol (0.375-3.5 g/kg) dose-dependently reduced spike activity in the PFC measured with multielectrode extracellular recording in the anesthetized rat. In an in vitro coculture system containing slices of PFC, hippocampus, and ventral tegmental area (VTA), ethanol (25-100 mM) decreased persistent activity of PFC neurons, but had little effect on firing evoked by direct current injection. Persistent activity was often enhanced after ethanol washout and this effect was maintained in cultures lacking the VTA. A low concentration of the NMDA antagonist APV (5 microM) mimicked the inhibition of ethanol of persistent activity with no change in activity after washout. Ethanol inhibition of spontaneous and VTA-evoked persistent activity was enhanced by the D1 dopamine receptor antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride]. The results of this study show that ethanol inhibits persistent activity and spike firing of PFC neurons and that the degree of ethanol inhibition may be influenced by D1 receptor tone. Ethanol-induced alterations in the activity of deep-layer cortical neurons may underlie some of the behavioral effects associated with ethanol intake.
Tu
Yali
Y
Department of Neurosciences and Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Kroener
Sven
S
Abernathy
Kenneth
K
Lapish
Christopher
C
Seamans
Jeremy
J
Chandler
L Judson
LJ
Woodward
John J
JJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018920:Coculture Techniques; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
D001552:Benzazepines; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate