title: Basolateral amygdala cdk5 activity mediates consolidation and reconsolidation of memories for cocaine cues.
abstract: Cocaine use and relapse involves learned associations between cocaine-associated environmental contexts and discrete stimuli and cocaine effects. Initially, these contextual and discrete cues undergo memory consolidation after being paired with cocaine exposure. During abstinence, cocaine cue memories can undergo memory reconsolidation after cue exposure without the drug. We used a conditioned place preference (CPP) procedure in rats to study the role of neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) in consolidation and reconsolidation of cocaine cue memories. We found that the expression of cocaine CPP in drug-free tests 1 d after CPP training (four pairings of 10 mg/kg cocaine with one context and four pairings of saline with a different context) increased Cdk5 activity, and levels of the Cdk5 activator p35 in basolateral but not central amygdala. We also found that basolateral (but not central) amygdala injections of the Cdk5 inhibitor beta-butyrolactone (100 ng/side) immediately (but not 6 h) after cocaine-context pairings during training prevented subsequent cocaine CPP expression. After training, acute basolateral (but not central) amygdala beta-butyrolactone injections immediately before testing prevented the expression of cocaine CPP; this effect was also observed on a second test performed 1 d later, suggesting an effect on reconsolidation of cocaine cue memories. In support, basolateral beta-butyrolactone injections, given immediately (but not 6 h) after a single exposure to the cocaine-paired context, prevented cocaine CPP expression 1 and 14 d after the injections. Results indicate that basolateral amygdala Cdk5 activity is critical for consolidation and reconsolidation of the memories of cocaine-associated environmental cues.
authors.affiliation: School of Pharmacy and Affiliated Hospital of Guiyang Medical University, Guiyang 550004, China.
authors.forename: Fang-qiong
authors.initials: FQ
authors.lastname: Li
authors.forename: Yan-xue
authors.initials: YX
authors.lastname: Xue
authors.forename: Ji-shi
authors.initials: JS
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Fang
authors.forename: Yan-qin
authors.initials: YQ
authors.lastname: Li
authors.forename: Wei-li
authors.initials: WL
authors.lastname: Zhu
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: He
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Liu
authors.forename: Li-fen
authors.initials: LF
authors.lastname: Xue
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D003042:Cocaine / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003463:Cues; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C013426:beta-butyrolactone; D051360:Cyclin-Dependent Kinase 5; D003042:Cocaine; D015107:4-Butyrolactone