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Adenosine Monophosphate-Activated Protein Kinase Regulates Reward Regions of the Brain During Cocaine Sensitization
Adenosine Monophosphate-Activated Protein Kinase Regulates Reward Regions of the Brain During Cocaine Sensitization
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202104831
- ISBN
- 9798293866557
- DDC
- 615
- 서명/저자
- Adenosine Monophosphate-Activated Protein Kinase Regulates Reward Regions of the Brain During Cocaine Sensitization
- 발행사항
- [Sl] : University of Minnesota, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 104 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
- 주기사항
- Advisor: Spencer, Sade.
- 학위논문주기
- Thesis (Ph.D.)--University of Minnesota, 2025.
- 초록/해제
- 요약Despite prevalent cocaine use there remains no FDA approved pharmacological treatment for cocaine use disorder. There is a critical need to identify mechanisms of addiction that can be targeted for treatment.Cocaine disrupts brain metabolism by depleting ATP (adenosine triphosphate) production. Given that adenosine monophosphate-activated protein kinase (AMPK) regulates ATP levels, it is worth investigating if cocaine disrupts its normal function. Previous studies showed changes in AMPK activity, marked by changes in phosphorylation state, associated with robust locomotor responses to cocaine. After cocaine sensitization, AMPK phosphorylation decreased in the dorsal striatum and increased in the prefrontal cortex, though only broad brain regions were investigated. Subregions of the prefrontal cortex, the prelimbic and infralimbic cortices, differentially regulate reward signaling. For example, the prelimbic cortex is known to be necessary for establishing cocaine sensitization while the infralimbic cortex is not. AMPK's role in cocaine sensitization remains understudied in these and other regions. There is a dearth of literature on AMPK in the VTA (ventral tegmental area) during cocaine sensitization despite the key role of the VTA in the development of sensitization. My thesis work here aimed to fill these gaps. I hypothesized that AMPK would respond similarly to cocaine sensitization in the VTA as in the striatum and that the prelimbic cortex would be the key area of increased AMPK activity in the prefrontal cortex. However, I found that AMPK did not change in the VTA after sensitization and phosphorylated AMPK in the prelimbic cortex was depleted after repeated cocaine. These changes appear to be independent of AMPK's kinase LKB1 (liver kinase B1). Based on the finding of decreased phosphorylated AMPK, I decided to test the effect of pharmacological manipulation of AMPK on expression of cocaine locomotor sensitization using AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and dorsomorphin to activate and inhibit AMPK, respectively. I observed that the common dosages for these drugs found in the literature were not potent enough to have an effect in the prelimbic cortex. The results of this project emphasize the further need to study AMPK in the context of sensitization. The unexpected results, especially the opposite directional change in the prelimbic than predicted, indicate the dynamic role of AMPK in addiction. Alternative sensitization schedules incorporating a withdrawal period and challenge dose as well as higher or more frequent doses of AMPK altering drugs would provide further elucidation into how AMPK regulates cocaine use disordered behavior.
- 일반주제명
- Pharmacology
- 일반주제명
- Neurosciences
- 일반주제명
- Behavioral sciences
- 키워드
- Addiction
- 키워드
- Locomotor
- 키워드
- Prelimbic cortex
- 기타저자
- University of Minnesota Pharmacology
- 기본자료저록
- Dissertations Abstracts International. 87-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■035 ▼a(MiAaPQ)AAI32170583
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a615
■1001 ▼aSchonfeld, Mark Alexander.
■24510▼aAdenosine Monophosphate-Activated Protein Kinase Regulates Reward Regions of the Brain During Cocaine Sensitization
■260 ▼a[Sl]▼bUniversity of Minnesota▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a104 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-03, Section: B.
■500 ▼aAdvisor: Spencer, Sade.
■5021 ▼aThesis (Ph.D.)--University of Minnesota, 2025.
■520 ▼aDespite prevalent cocaine use there remains no FDA approved pharmacological treatment for cocaine use disorder. There is a critical need to identify mechanisms of addiction that can be targeted for treatment.Cocaine disrupts brain metabolism by depleting ATP (adenosine triphosphate) production. Given that adenosine monophosphate-activated protein kinase (AMPK) regulates ATP levels, it is worth investigating if cocaine disrupts its normal function. Previous studies showed changes in AMPK activity, marked by changes in phosphorylation state, associated with robust locomotor responses to cocaine. After cocaine sensitization, AMPK phosphorylation decreased in the dorsal striatum and increased in the prefrontal cortex, though only broad brain regions were investigated. Subregions of the prefrontal cortex, the prelimbic and infralimbic cortices, differentially regulate reward signaling. For example, the prelimbic cortex is known to be necessary for establishing cocaine sensitization while the infralimbic cortex is not. AMPK's role in cocaine sensitization remains understudied in these and other regions. There is a dearth of literature on AMPK in the VTA (ventral tegmental area) during cocaine sensitization despite the key role of the VTA in the development of sensitization. My thesis work here aimed to fill these gaps. I hypothesized that AMPK would respond similarly to cocaine sensitization in the VTA as in the striatum and that the prelimbic cortex would be the key area of increased AMPK activity in the prefrontal cortex. However, I found that AMPK did not change in the VTA after sensitization and phosphorylated AMPK in the prelimbic cortex was depleted after repeated cocaine. These changes appear to be independent of AMPK's kinase LKB1 (liver kinase B1). Based on the finding of decreased phosphorylated AMPK, I decided to test the effect of pharmacological manipulation of AMPK on expression of cocaine locomotor sensitization using AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) and dorsomorphin to activate and inhibit AMPK, respectively. I observed that the common dosages for these drugs found in the literature were not potent enough to have an effect in the prelimbic cortex. The results of this project emphasize the further need to study AMPK in the context of sensitization. The unexpected results, especially the opposite directional change in the prelimbic than predicted, indicate the dynamic role of AMPK in addiction. Alternative sensitization schedules incorporating a withdrawal period and challenge dose as well as higher or more frequent doses of AMPK altering drugs would provide further elucidation into how AMPK regulates cocaine use disordered behavior.
■590 ▼aSchool code: 0130.
■650 4▼aPharmacology
■650 4▼aNeurosciences
■650 4▼aBehavioral sciences
■653 ▼aAddiction
■653 ▼aCocaine sensitization
■653 ▼aLocomotor
■653 ▼aPrelimbic cortex
■653 ▼aPharmacological manipulation
■690 ▼a0419
■690 ▼a0317
■690 ▼a0602
■71020▼aUniversity of Minnesota▼bPharmacology.
■7730 ▼tDissertations Abstracts International▼g87-03B.
■790 ▼a0130
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359075▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
