Long-term potentiation (LTP) in the central amygdala (CeA) is enhanced after prolonged withdrawal from chronic cocaine and requires CRF1 receptors.
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.
Fu
Yu
Y
Department of Pharmacology and Toxicology, Medical Branch, University of Texas, 301 University Blvd., Galveston, TX 77555-1031, USA.
Pollandt
Sebastian
S
Liu
Jie
J
Krishnan
Balaji
B
Genzer
Kathy
K
Orozco-Cabal
Luis
L
Gallagher
Joel P
JP
Shinnick-Gallagher
Patricia
P
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
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