title: Chronic intermittent ethanol and withdrawal differentially modulate basolateral amygdala AMPA-type glutamate receptor function and trafficking.
abstract: The amygdala plays a critical role in the generation and expression of anxiety-like behaviors including those expressed following withdrawal (WD) from chronic intermittent ethanol (CIE) exposure. In particular, the BLA glutamatergic system controls the expression of both innate and pathological anxiety. Recent data suggests that CIE and WD may functionally alter this system in a manner that closely parallels memory-related phenomena like long-term potentiation (LTP). We therefore specifically dissected CIE/WD-induced changes in glutamatergic signaling using electrophysiological and biochemical approaches with a particular focus on the plasticity-related components of this neurotransmitter system. Our results indicate that cortical glutamatergic inputs arriving at BLA principal via the external capsule undergo predominantly post-synaptic alterations in AMPA receptor function following CIE and WD. Biochemical analysis revealed treatment-dependent changes in AMPA receptor surface expression and subunit phosphorylation that are complemented by changes in total protein levels and/or phosphorylation status of several key, plasticity-associated protein kinases such as calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC). Together, these data show that CIE- and WD-induced changes in BLA glutamatergic function both functionally and biochemically mimic plasticity-related states. These mechanisms likely contribute to long-term increases in anxiety-like behavior following chronic ethanol exposure.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Christian
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Alexander
authors.forename: Marvin R
authors.initials: MR
authors.lastname: Diaz
authors.forename: Stacey
authors.initials: S
authors.lastname: Robinson
authors.forename: Brian A
authors.initials: BA
authors.lastname: McCool
mesh_terms: D000679:Amygdala / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009924:Organ Culture Techniques; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D000431:Ethanol