title: Dopamine receptor mechanisms mediate corticotropin-releasing factor-induced long-term potentiation in the rat amygdala following cocaine withdrawal.
abstract: Corticotropin-releasing factor (CRF) in the amygdala is involved in stress responses. Moreover, dopaminergic neurotransmission in the brain reward system including the amygdala plays a significant role in the pathology of cocaine addiction. The present study analysed CRF-induced synaptic plasticity, its pharmacological sensitivity and interactions with the dopamine (DA) system in the basolateral to lateral capsula central amygdala (lcCeA) pathway after a 2-week withdrawal from repeated cocaine administration. A physiologically relevant CRF concentration (25 nm) induced long-term potentiation (LTP) that was enhanced after cocaine withdrawal. In saline-treated rats, CRF-induced LTP was mediated through N-methyl-d-aspartate (NMDA) receptors, L-type voltage-gated calcium channels (L-VGCCs) and CRF(1) receptors. However, in cocaine-withdrawn animals, activation of CRF(1) and CRF(2) receptors was found to enhance LTP. This enhanced CRF-induced LTP after cocaine withdrawal was mediated through endogenous activation of both D1- and D2-like receptors. Furthermore, expression of the D1 receptor (D1R) but not the D2R, D3R, D4R or D5R was significantly increased after cocaine withdrawal. CRF(1) but not CRF(2) protein expression was increased, suggesting that elevated levels of these proteins contributed to the enhancement of CRF-induced LTP during cocaine withdrawal. CRF interactions with the DA system in the amygdala may represent a fundamental neurochemical and cellular mechanism linking stress to cocaine-induced neuronal plasticity.
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA. bakrishn@utmb.edu
authors.forename: Balaji
authors.initials: B
authors.lastname: Krishnan
authors.forename: Marjorie
authors.initials: M
authors.lastname: Centeno
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pollandt
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.forename: Kathy
authors.initials: K
authors.lastname: Genzer
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
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; D003042:Cocaine / Q000009:adverse effects / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000473:pathology*; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D011954:Receptors, Dopamine; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine