Gene expression of conditioned locomotion and context-specific locomotor sensitization controlled by morphine-associated environment.
The nucleus accumbens (NAc) is involved in contextual drug associations, which might be particularly important for environmental cue-induced relapse to drug seeking. In the present study, rats were first administered repeated morphine for 5 days (5 mg/kg, i.p.) in a contextually paired and unpaired design. After reexposure to the morphine-associated environment, which induced conditioned locomotor activity in the morphine-paired group, we performed a rat 27k 70-mer oligo array to profile gene expression in the NAc. One hundred fifty-five upregulated and 88 downregulated genes were found in the paired group compared with the unpaired group. Eight gene transcripts were then selected to confirm their alterations by quantitative real-time polymerase chain reaction (qRT-PCR). The identified genes generally play important roles in neuroactive receptor-ligand interactions, synapse plasticity, ion transport, and protein phosphorylation. Furthermore, the expression of the eight selected genes that were identified and confirmed to show significant fold changes in the first microarray experiment were again measured with qRT-PCR after morphine challenge (2 mg/kg, i.p.). As expected, 2 mg/kg morphine-induced context-specific sensitization. Meanwhile, mRNA expression of the selected genes showed marked upregulation in the morphine-paired group compared with the unpaired and acute groups. These results suggest that alterations in the expression of the identified genes in the NAc may contribute to the neuroplasticity underlying contextual cue-induced relapse to drug use.
Liang
Jing
J
Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beishatan, Chaoyang District, Beijing 100101, PR China.
Chen
Ji-Huan
JH
Chen
Xiao-Hong
XH
Peng
Yong-Hua
YH
Zheng
Xi-Geng
XG
D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D003463:Cues; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D009020:Morphine