A novel model of oxycodone seeking that considers sex and stress susceptibility.
一种考虑性别和压力敏感性的羟考酮寻求新模型。
基本信息
- 批准号:10057442
- 负责人:
- 金额:$ 7.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-15 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:Alcohol or Other Drugs useAlcoholsAmygdaloid structureAnhedoniaAnimal ModelAnimalsAnxietyBehaviorBiologicalCocaineCuesDiagnosisDiseaseExposure toExtinction (Psychology)FemaleFundingFutureGRM5 geneGeneral PopulationGoalsHumanImpairmentIndividualIndividual DifferencesInfusion proceduresInterventionIntravenousLeadMediatingMethodologyModelingNeurobiologyOpioidOxycodonePatientsPharmaceutical PreparationsPharmacotherapyPhenotypePopulationPost-Traumatic Stress DisordersPredispositionPrefrontal CortexPrevalencePriceRattusRelapseResearchResearch ProposalsResistanceRewardsRodentSelf AdministrationSex DifferencesStressSubstance Use DisorderSymptomsTherapeuticTimeTraumaWorkacute stressanimal model developmentanxiety symptomsanxiouscocaine usecomorbiditycostdesigndrug cravingdrug of abusemaleneuroadaptationnovelopioid abuseopioid use disorderpost-traumaresponsesexstressortherapy developmenttrauma exposuretraumatic event
项目摘要
ABSTRACT
Post-traumatic stress disorder (PTSD) is a debilitating disorder that develops in a subpopulation (~20-30%) of
people exposed to a traumatic event. PTSD is highly comorbid with substance use disorder (SUD), with alcohol,
stimulants and opioids being the most frequently abused drugs. Despite the prevalence of PTSD+SUD
comorbidity, animal models of such comorbidity are lacking and are sorely needed to screen potential treatments.
Here we will utilize our novel animal model of PTSD+SUD that captures several key features of PTSD+SUD
comorbidity: 1) PTSD typically arises from a single trauma, 2) not all trauma-exposed individuals develop PTSD,
3) post-trauma anxiety symptoms are long-lasting, and 4) increased drug-craving and resistance to traditional
interventions that reduce relapse in SUD. This model relies on exposing rodents to an ethologically-relevant
“trauma” - predator scent stress (PSS). We have successfully combined the PSS model of PTSD with the
extended access to cocaine self-administration to study PTSD+cocaine use disorder (CUD) in animals. The
present application proposes to adapt this animal model to study the interaction between opioid use disorder
(OUD) and PTSD. Our overall hypothesis is that, as we demonstrated for cocaine, stress-Susceptible rats will
display greater oxycodone seeking, a possible indication of similar neurobiological underpinnings of both cocaine
and opioid seeking in stress susceptible rats. We will assess opioid seeking using two models. Aim 1 will utilize
demand curve analyses (increasing the “cost” to obtain intravenous oxycodone infusions over days) to calculate
the essential demand for oxycodone and use regression models to assess the relationship between anxiety and
oxycodone demand. This work will be done in males and females, and thus, will be the first work to assess sex
differences in demand for oxycodone. We have found that stress-susceptibility results in increased cue-primed
reinstatement of cocaine-seeking and impaired instrumental extinction of the response made to obtain cocaine.
Aim 2 will assess if the same is true for oxycodone seeking, which would imply a common circuit or circuits
mediating enhanced stress susceptibility and drug-seeking and potentially lead to pharmacotherapies for
individuals with both OUD and CUD. Our rationale is that rat models that more closely model comorbidities
accompanying human substance use should more accurately reproduce the underlying neuroadaptations
present in humans, and should thus serve as better platforms for therapeutic discovery. As such, our central,
unified hypothesis is that susceptibility to stress remodels circuits involved in drug seeking in a similar manner
for cocaine and opioids. Future research proposals would interrogate neurobiological substrates and circuit(s)
involved in differential oxycodone seeking. For example, we have found that mGlu5 expression in the amygdala
and prefrontal cortex is increased in Resilient rats relative to Susceptible rats after re-exposure to the TMT
context, two regions also implicated in extinction and seeking of drugs of abuse.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Marek Schwendt其他文献
Marek Schwendt的其他文献
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{{ truncateString('Marek Schwendt', 18)}}的其他基金
A novel model of oxycodone seeking that considers sex and stress susceptibility
一种考虑性别和压力敏感性的羟考酮寻求新模型
- 批准号:
10399874 - 财政年份:2021
- 资助金额:
$ 7.63万 - 项目类别:
A novel model of oxycodone seeking that considers sex and stress susceptibility.
一种考虑性别和压力敏感性的羟考酮寻求新模型。
- 批准号:
10183214 - 财政年份:2020
- 资助金额:
$ 7.63万 - 项目类别:
Developing novel tools for targeting mGlu2(3) receptors in methamphetamine addiction.
开发针对甲基苯丙胺成瘾中的 mGlu2(3) 受体的新工具。
- 批准号:
9806929 - 财政年份:2019
- 资助金额:
$ 7.63万 - 项目类别:
Striatal RGS4 Interacts with mGluR5 Signaling in Relapse to Cocaine-seeking
纹状体 RGS4 与 mGluR5 信号相互作用导致可卡因寻求复发
- 批准号:
7788579 - 财政年份:2010
- 资助金额:
$ 7.63万 - 项目类别:
Striatal RGS4 Interacts with mGluR5 Signaling in Relapse to Cocaine-seeking
纹状体 RGS4 与 mGluR5 信号相互作用导致可卡因寻求复发
- 批准号:
8027727 - 财政年份:2010
- 资助金额:
$ 7.63万 - 项目类别:
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