[대학원 생명과학과 세미나 안내]
연사 : 김정훈 교수 (포항공대 생명과학과)
연제 : Dopamine-dependent cholinergic control for susceptibility to cocaine addiction
일시 : 2019년 6월 14일 (금) 오후 5시
장소 : 하나과학관 A동 B131호
초청교수 : 백자현 교수
Abstract
We are much interested in cellular & molecular mechanisms underlying memory persistence and the ongoing modification. Out of them, we have carried out experiments to parse cellular mechanisms underlying sustained seeking behaviors that would arise after repeated usage of psychostimulants such as cocaine. We first attempted to assess and quantify the seeking behavior of mice under progressive ratio schedule of cocaine self-administration, which enabled us to divide subject animals into two groups: susceptible mice that exhibited craving behaviors to cocaine infusion and resilient ones that did not show compulsive cocaine seeking. Striatal cholinergic interneurons (ChINs) play critical roles in processing of reward-related information, mainly by controlling the medium spiny neurons (MSNs) of the nucleus accumbens (NAc). We found that in vivo activity of accumbal ChINs was increased by cocaine injection in drug-naïve and resilient mice, but it was different to cocaine in susceptible mice. Cell-type-specific RNA sequencing of striatal regions from susceptible and resilient mice, produced a number of DEGs between two groups. Our transcriptome and physiological analyses indicated that ChINs in the NAc displayed higher abundance of dopamine D2 receptor (DrD2) in the susceptible mice, compared to those in the resilient animals. A series of experiments revealed substantial evidence that increased abundance of DrD2 at ChINs is necessary and sufficient for occurrence of susceptibility traits to cocaine infusion. Collectively, our data provide novel mechanistic insights into the susceptibility to cocaine addiction and ultimately contribute to the development and refinement of therapeutic interventions to these types of disorders.