title: Long-term potentiation (LTP) in the central amygdala (CeA) is enhanced after prolonged withdrawal from chronic cocaine and requires CRF1 receptors.
abstract: The amygdala is part of the brain reward circuitry that plays a role in cocaine-seeking and abstinence in animals and cocaine craving and relapse in humans. Cocaine-seeking is elicited by cocaine-associated cues, and the basolateral amygdala (BLA) and CeA are essential in forming and communicating drug-related associations that are thought to be critical in long-lasting relapse risk associated with drug addiction. Here we simulated a cue stimulus with high-frequency stimulation (HFS) of the BLA-CeA pathway to examine mechanisms that may contribute to drug-related associations. We found enhanced long-term potentiation (LTP) after 14-day but not 1-day withdrawal from 7-day cocaine treatment mediated through N-methyl-d-aspartate (NMDA) receptors (NRs), L-type voltage-gated calcium channels (L-VGCCs), and corticotropin-releasing factor (CRF)(1) receptors; this was accompanied by increased phosphorylated NR1 and CRF(1) protein not associated with changes in NMDA/AMPA ratios in amygdalae from cocaine-treated animals. We suggest that these signaling mechanisms may provide therapeutic targets for the treatment of cocaine cravings.
authors.affiliation: Department of Pharmacology and Toxicology, Medical Branch, University of Texas, 301 University Blvd., Galveston, TX 77555-1031, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pollandt
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Balaji
authors.initials: B
authors.lastname: Krishnan
authors.forename: Kathy
authors.initials: K
authors.lastname: Genzer
authors.forename: Luis
authors.initials: L
authors.lastname: Orozco-Cabal
authors.forename: Joel P
authors.initials: JP
authors.lastname: Gallagher
authors.forename: Patricia
authors.initials: P
authors.lastname: Shinnick-Gallagher
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003042:Cocaine / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003463:Cues; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013997:Time Factors; D000099052:CRF Receptor, Type 1
chemical_list: D020746:Calcium Channels, L-Type; D018765:Dopamine Uptake Inhibitors; C409466:NR1 NMDA receptor; D018019:Receptors, Corticotropin-Releasing Hormone; D016194:Receptors, N-Methyl-D-Aspartate; D000099052:CRF Receptor, Type 1; D003042:Cocaine