Abstract

The development of ethanol tolerance and dependence reflects neuroadaptive changes in response to continuous depression in synaptic activity. The present study used confocal imaging and electrophysiology procedures to assess the effects of prolonged ethanol exposure on NMDA receptor trafficking in cultures of hippocampal neurons. Neurons exposed to 50 mm ethanol for 4 d showed an increase in the colocalization of NMDA receptor type 1 (NR1) clusters with the presynaptic marker protein synapsin. This was accompanied by significant increases in the size and density of these synapsin-associated clusters with no change observed in nonsynapsin-associated NR1 clusters. Similar effects were observed with NR2B clustering after chronic ethanol exposure. The increase in synaptic NMDA receptor clustering was prevented by addition of a protein kinase A inhibitor or by coexposure to a low concentration of NMDA and was reversed when ethanol was removed from the cultures. No changes were observed in the synaptic content, cluster size, or density of AMPA receptors after ethanol exposure. Electrophysiological measurements on ethanol-treated neurons revealed a similar enhancement in synaptic NMDA currents with no change in AMPA-mediated events. After isolation of extrasynaptic NMDA receptors by MK801 (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (/) trapping, whole-cell responses to NMDA were not different between control and ethanol-treated neurons These observations demonstrate that neuroadaptive changes in NMDA receptors in response to prolonged ethanol exposure occur through activity-dependent processes that regulate their synaptic targeting and localization.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.