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MeBib Suppressed Methamphetamine Self-Administration Response via Inhibition of BDNF/ERK/CREB Signal Pathway in the Hippocampus

Biomolecules & Therapeutics 2020년 28권 6호 p.519 ~ 526
Kim Bu-Yun, 자소남, Seo Ji-Hae, 정철호, 이수연, 이상길, 서영호, 박병덕,
소속 상세정보
 ( Kim Bu-Yun ) - Keimyung University College of Pharmacy
자소남 ( Jha So-Nam ) - Keimyung University College of Pharmacy
 ( Seo Ji-Hae ) - Keimyung University School of Medicine Department of Biochemistry
정철호 ( Jeong Chul-Ho ) - Keimyung University College of Pharmacy
이수연 ( Lee Soo-Yeun ) - Keimyung University College of Pharmacy
이상길 ( Lee Sang-Kil ) - Keimyung University College of Pharmacy
서영호 ( Seo Young-Ho ) - Keimyung University College of Pharmacy
박병덕 ( Park Byoung-Duck ) - Keimyung University College of Pharmacy

Abstract


Methamphetamine (MA) is one of the most commonly abused drugs in the world by illegal drug users. Addiction to MA is a serious public health problem and effective therapies do not exist to date. It has also been reported that behavior induced by psychostimulants such as MA is related to histone deacetylase (HDAC). MeBib is an HDAC6 inhibitor derived from a benzimidazole scaffold. Many benzimidazole-containing compounds exhibit a wide range of pharmacological activity. In this study, we investigated whether HDAC6 inhibitor MeBib modulates the behavioral response in MA self-administered rats. Our results demonstrated that the number of active lever presses in MA self-administered rats was reduced by pretreatment with MeBib. In the hippocampus of rats, we also found MA administration promotes GluN2B, an NMDA receptor subunit, expression, which results in sequential activation of ERK/CREB/BDNF pathway, however, MeBib abrogated it. Collectively, we suggest that MeBib prevents the MA seeking response induced by MA administration and therefore, represents a potent candidate as an MA addiction inhibitor.

키워드

Methamphetamine; Self-administration; MeBib; HDAC6 inhibitor; Hippocampus

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