Neurobiology of Ketamine Addiction
Neurobiology of Ketamine Addiction
批准号:
10471826
负责人:
MOHAMED KABBAJ
金额:
$37.1万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-30 至 2024-08-31
关键词:
AcuteAdultAlcohol abuseAlcohol consumptionAlcoholsAnalgesicsAntidepressive AgentsBehaviorBehavioralBipolar DisorderBrainCannabinoidsChronicClinicalClinical ResearchCocaine DependenceDataDiestrusDoseDrug AddictionDrug usageEstrogensExposure toFeeling suicidalFemaleGenderHormonalHousingHumanImpaired cognitionInfusion proceduresInjectionsIntravenousKetamineLabelLiteratureMajor Depressive DisorderMediatingMental DepressionModelingMolecularMusN-Methyl-D-Aspartate ReceptorsNeurobiologyNeuronsNicotineNucleus AccumbensOpioidOutcomeOvarianPathologyPharmaceutical PreparationsPhasePhencyclidinePhysiological AdaptationPlayPopulationPost-Traumatic Stress DisordersProestrusProgesteronePropertyPsychological reinforcementPsychopathologyPsychotropic DrugsRattusRecording of previous eventsRegimenRelapseReportingResolutionRewardsRodentRoleSafetySelf AdministrationSex DifferencesSocial isolationStressSynapsesTestingTherapeutic EffectTransgenic OrganismsWomanWorkabuse liabilityaddictionalcohol exposureantagonistantidepressant effectanxiety-like behaviorbehavioral plasticitybehavioral sensitizationcomorbid depressioncomorbiditydepressed patientdrug of abusegender differencemalemenneurotoxicitypre-clinicalpreclinical studypreventpsychostimulantresponsesexsocial grouptreatment-resistant depression
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
A single injection of small dose of ketamine induced a rapid resolution of suicidal ideation.
Since acute ketamine effects are short lived, recent clinical studies are testing whether
subchronic treatments with ketamine can prevent relapse to depression. The results of these
studies are promising as they clearly show that repeated ketamine infusions achieved superior
outcome when compared to acute treatment. It is clear therefore that the viability of ketamine
as an antidepressant treatment will necessitate repeated infusions of small doses under a
chronic regimen. The safety of such treatments is still not very clear when one acknowledges
that ketamine is considered a drug of abuse. Furthermore, the comorbidity of depression with
other drugs of abuse, especially alcohol adds further complications to the viability of ketamine
as a treatment for depression. Finally, the effects of ketamine in both sexes are still
understudied. The ketamine doses that are used to treat Treatment Resistant Depression
[TRD] in humans work for both sexes and, so far, there were no efforts made to examine the
antidepressant effects of lower doses of ketamine in women. This is despite some evidence in
humans showing that ketamine use leads to severe cognitive impairments in women when
compared to men and some evidence in rodents, showing higher sensitivity of female rodents to
the analgesic and the antidepressant effects of ketamine. In rodents, ketamine also leads to
greater neurotoxicity in females when compared to males. Accordingly, it is critical that further
clinical and preclinical studies examine the safety of repeated treatments with low doses of
ketamine, in both sexes, before approving ketamine as a safe treatment for TRD. Through this
application we shall answer very specific questions about the safety of long term treatment with
ketamine: 1- In both sexes, do repeated treatments with low doses of ketamine induce
addictive-like behaviors? 2- Does female hormonal status play a role in response to ketamine's
addictive properties?; 3- Does alcohol abuse enhance the addictive properties of ketamine in
either sex? 4- What are the physiological adaptations that occur in the brain with repeated
ketamine treatments? We truly believe that the response to these questions will inform clinicians
about the safety or not of chronic ketamine treatment for TRD.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
Sex and Individual Differences in Alcohol Intake Are Associated with Differences in Ketamine Self-Administration Behaviors and Nucleus Accumbens Dendritic Spine Density.
酒精摄入量的性别和个体差异与氯胺酮自我给药行为和伏核树突棘密度的差异有关。
DOI:
10.1523/eneuro.0221-19.2019
发表时间:
2019
期刊:
eNeuro
影响因子:
3.4
作者:
[Strong,CarolineE, Wright,KatherineN, Kabbaj,Mohamed]
通讯作者:
Kabbaj,Mohamed
DOI:
10.3389/fnbeh.2020.593860
发表时间:
2020
期刊:
Frontiers in behavioral neuroscience
影响因子:
3
作者:
[Strong CE, Kabbaj M]
通讯作者:
Kabbaj M
Breaking bonds in prairie voles
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批准号:10373253
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项目类别:
-
资助金额:$61.15万
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财政年份:2022
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负责人:MOHAMED KABBAJ
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依托单位:
Breaking bonds in prairie voles
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批准号:10581709
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项目类别:
-
资助金额:$60.07万
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财政年份:2022
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负责人:MOHAMED KABBAJ
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依托单位:
Neurobiology of Ketamine Addiction
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批准号:10229544
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项目类别:
-
资助金额:$37.15万
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财政年份:2018
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负责人:MOHAMED KABBAJ
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依托单位:
Epigenetics of social bonding in prairie voles
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批准号:9489311
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项目类别:
-
资助金额:$38.0万
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财政年份:2016
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负责人:MOHAMED KABBAJ
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依托单位:
Sex Differences in Ketamine Antidepressant Effects
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批准号:8826814
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项目类别:
-
资助金额:$37.14万
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财政年份:2013
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负责人:MOHAMED KABBAJ
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依托单位:
Sex Differences in Ketamine Antidepressant Effects
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批准号:9036446
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项目类别:
-
资助金额:$38.0万
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财政年份:2013
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负责人:MOHAMED KABBAJ
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依托单位:
Sex Differences in Ketamine Antidepressant Effects
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批准号:8583138
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项目类别:
-
资助金额:$37.18万
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财政年份:2013
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负责人:MOHAMED KABBAJ
-
依托单位:
Sex Differences in Ketamine Antidepressant Effects
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批准号:9247036
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项目类别:
-
资助金额:$38.0万
-
财政年份:2013
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负责人:MOHAMED KABBAJ
-
依托单位:
Sex Differences in Ketamine Antidepressant Effects
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批准号:8686960
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项目类别:
-
资助金额:$37.21万
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财政年份:2013
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负责人:MOHAMED KABBAJ
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依托单位:
Sex Differences In Anxiety: Role of Zif268
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批准号:8247156
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项目类别:
-
资助金额:$35.37万
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财政年份:2010
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负责人:MOHAMED KABBAJ
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依托单位:
Sex Differences In Anxiety: Role of Zif268
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批准号:8425081
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项目类别:
-
资助金额:$33.81万
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财政年份:2010
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负责人:MOHAMED KABBAJ
-
依托单位:
Sex Differences In Anxiety: Role of Zif268
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批准号:8105454
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项目类别:
-
资助金额:$35.5万
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财政年份:2010
-
负责人:MOHAMED KABBAJ
-
依托单位:
Sex Differences In Anxiety: Role of Zif268
-
批准号:8625828
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项目类别:
-
资助金额:$35.04万
-
财政年份:2010
-
负责人:MOHAMED KABBAJ
-
依托单位:
Sex Differences In Anxiety: Role of Zif268
-
批准号:7984694
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项目类别:
-
资助金额:$35.98万
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财政年份:2010
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负责人:MOHAMED KABBAJ
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依托单位:
Epigenetics of Social Defeat
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批准号:7659893
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项目类别:
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资助金额:$21.74万
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财政年份:2009
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负责人:MOHAMED KABBAJ
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依托单位:
Epigenetics of Social Bonding
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批准号:7995255
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项目类别:
-
资助金额:$21.83万
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财政年份:2009
-
负责人:MOHAMED KABBAJ
-
依托单位:
Epigenetics of Social Defeat
-
批准号:7799815
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项目类别:
-
资助金额:$18.03万
-
财政年份:2009
-
负责人:MOHAMED KABBAJ
-
依托单位:
Epigenetics of Social Bonding
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批准号:7787670
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项目类别:
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资助金额:$18.38万
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财政年份:2009
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负责人:MOHAMED KABBAJ
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依托单位:
Individual differences in anxiety in females
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批准号:7030117
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项目类别:
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资助金额:$7.17万
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财政年份:2005
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负责人:MOHAMED KABBAJ
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依托单位:
Individual differences in anxiety in females
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批准号:7128143
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项目类别:
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资助金额:$6.99万
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财政年份:2005
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负责人:MOHAMED KABBAJ
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依托单位:
海外基金