Activation of amygdaloid PKC pathway is necessary for conditioned cues-provoked cocaine memory performance.
Drug-associated cues are critical in reinstating the drug taking behavior even during prolonged abstinence and thus are thought to be a key factor to induce drug craving and to cause relapse. Amygdaloid complex has been known for its physiological function in mediating emotional experience storage and emotional cues-regulated memory retrieval. This study was undertaken to examine the role of basolateral nuclei of amygdala and the intracellular signaling molecule in drug cues-elicited cocaine memory retrieval. Systemic anisomycin treatment prior to the retrieval test abolished the cues-provoked cocaine conditioned place preference (CPP) memory. Likewise, a similar blockade of cues-provoked cocaine CPP performance was achieved by infusion of anisomycin and cycloheximide into the basolateral nuclei of amygdala before the test. Intra-amygdaloid infusion of H89, a protein kinase A inhibitor, or U0126, a MEK inhibitor, did not affect retrieval of the cues-elicited cocaine CPP memory. In contrast, intra-amygdaloid infusion of NPC 15437, a PKC inhibitor, abolished the cues-elicited cocaine CPP expression, while left the memory per se intact. Intra-amygdaloid infusion of NPC 15437 did not seem to affect locomotor activity or exert observable aversive effect. Taken together, our results suggest that activation of PKC signaling pathway and probably downstream de novo protein synthesis in the basolateral nuclei of amygdala is required for the cues-elicited cocaine memory performance. However, temporary inhibition of this signaling pathway does not seem to affect cocaine CPP memory per se.
Lai
Yu-Ting
YT
Behavioral Neuropharmacology Laboratory, Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, 1 University Road, Tainan 701, Taiwan, ROC.
Fan
Hsin-Yi
HY
Cherng
Chianfang G
CG
Chiang
Chih-Yuan
CY
Kao
Gour-Shenq
GS
Yu
Lung
L
D000679:Amygdala / Q000187:drug effects* / Q000201:enzymology*; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology
D018765:Dopamine Uptake Inhibitors; D007546:Isoquinolines; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D013449:Sulfonamides; C069701:NPC 15437; D000841:Anisomycin; D003513:Cycloheximide; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide