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Disruption of amphetamine sensitization by alteration of dendritic thin spines in the nucleus accumbens core

 Wen Ting Cai  ;  Wha Young Kim  ;  Myung Ji Kwak  ;  Haeun Rim  ;  Seung Eun Lee  ;  Lars Björn Riecken  ;  Helen Morrison  ;  Jeong-Hoon Kim 
 JOURNAL OF NEUROCHEMISTRY, Vol.161(3) : 266-280, 2022-05 
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Issue Date
Amphetamine* / pharmacology ; Animals ; Brain ; Central Nervous System Stimulants* / pharmacology ; Nucleus Accumbens ; Rats
amphetamine ; dendritic spine ; locomotor sensitization ; nucleus accumbens ; radixin
Repeated injections of psychomotor stimulants like amphetamine (AMPH) to rodents can induce behavioral sensitization, which represents a long-lasting craving that is usually observed in human addicts. Behavioral sensitization is characteristically maintained for a long duration, accompanied by structural plasticity in some brain areas involved in reward circuitry. For example, it increased dendritic spine densities in the nucleus accumbens (NAcc), which is considered to reflect neurophysiological changes at this site, leading to addictive behaviors. The ezrin, radixin, and moesin (ERM) proteins regulate spine maturity by modifying their phosphorylation at the C-terminal region. We previously showed that ERM phosphorylation is reduced by AMPH in the NAcc core, suggesting that ERM-mediated spine changes at this site might be associated with AMPH sensitization. To test this hypothesis, we administered AMPH to rats according to a sensitization development schedule, with lentivirus encoding a phosphomimetic pseudo-active mutant of radixin (Rdx T564D) in the NAcc core, and examined dendritic spines at this site. We found that compared to acute AMPH, AMPH sensitization increased thin spine density with a similar ratio of filopodia-like to mature thin spines. However, with Rdx T564D, the density of thin spines increased, with augmented filopodia-like thin spines, resulting in no AMPH sensitization. These results indicate that Rdx T564D forces thin spines to immaturity and thereby inhibits AMPH sensitization, for which an increase in mature thin spines is normally necessary. These findings provide significant clues to our understanding of the role of dendritic spines in mediating the development of psychomotor stimulant addiction.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jeong Hoon(김정훈) ORCID logo https://orcid.org/0000-0001-7095-3729
Kim, Wha Young(김화영) ORCID logo https://orcid.org/0000-0003-1744-7012
Cai, Wen Ting(채문정)
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