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- Title
Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological target of behavioural sensitization to morphine in rats.
- Authors
Yan-Ting Wang; Wang-Jun Qin; Qing Liu; Yu-Ling Li; Hui Liang; Feng Chen; Lawrence, Andrew J.; Xiang-Lin Zhang; Jian-Hui Liang
- Abstract
Drug addiction is a major public health issue, yet the underlying adaptation of neural networks by drugs of abuse is not fully understood. We have previously linked chaperone heat shock protein 70 (Hsp70) to drug-induced adaptations. Focusing on the NAc core and shell, the present study aims to provide further findings for our understanding of the relation between behavioural sensitization to morphine and Hsp70 at transcrip-tional and functional levels in rats. Firstly, we delineated the characteristics of behavioural sensitization induced by a single morphine exposure (1-10 mg/kg, s.c.). Secondly, Hsp70 protein expression in the NAc core was time-and dose-relatedly induced during the development of behavioural sensitization to a single morphine exposure in rats, and Pearson analysis indicated a positive correlation between behavioural sensitization and Hsp70 ex-pression in NAc core. Thirdly, at the transcriptional level, intra-NAc core injection of the specific heat shock fac-tor-I (HSF-I) inhibitor N-Formyl-3,4-methylenedioxy-benzylidine-j'-butyrolactam (KNK437) suppressed Hsp70 expression and the development of behavioural sensitization, while the HSF-I specific inducer geranylgeranyla-cetone (GGA) promoted both of them. Interestingly, intra-NAc shell injection of KNK437 or GGA did not affect the development of behavioural sensitization. Finally, both the functional inhibition of Hsp70 ATPase activity by methylene blue (MB), and the antagonism of Hsp70 substrate binding site (SBD) activity by pifithrin-/i (PES) impaired the development of behavioural sensitization when they were microinjected into the NAc core. Taken together, the critical involvement of chaperone Hsp70 in behavioural sensitization to morphine identifies a biological target for long-lasting adaptations with relevance to addiction.
- Subjects
TARGETED drug delivery; HEAT shock proteins; MOLECULAR chaperones; NUCLEUS accumbens; DRUG addiction; NEURAL circuitry; PUBLIC health; SENSITIZATION (Neuropsychology); MORPHINE; LABORATORY rats; PHYSIOLOGY
- Publication
International Journal of Neuropsychopharmacology, 2014, Vol 17, Issue 3, p469
- ISSN
1461-1457
- Publication type
Article
- DOI
10.1017/S1461145713001429