Name: a general method for evaluating deep brain stimulation effects on intravenous methamphetamine self-administration
Uploaded: 2016-01-22T13:00:00.000+00:00
Duration: 9 min 16 s
Description: Watch this Scientific Journal Video about A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration at JoVE.com

Supported by the 2014-2015 Neurosurgery Research and Education Foundation (NREF) award and a 2014 Grant-In-Aid Award from Louisiana State University Shreveport School of Medicine (J.A.W.). We thank S. Harold and C.M. Keller for their invaluable technical assistance and teaching.

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The authors have no competing financial interests with regards to this methodology.

뇌 심부 자극술의 정확한 메커니즘이 완전히 특징되지 않지만, 모터와 정신 질환 모두 DBS의 효과는 전기 치료와 시간 6,22-26을 통해 다양한 피질과 대뇌 피질의 뇌 영역의 기능 사이의 역동적 인 상호 작용이 발생할 수 있습니다. 설치류에 필로폰 전달의 비 조건부 방법은 27,28 잘 설명되어 있지만,이 방법은 약물의 약물 동태 학 및 신경 화학적 효과 27 ~ 29의 개별 연구에 가장 적합합니다. 조작 적 IV 약물 자기 관리는 약물에 대한 동기 부여의 요소를 통합하여, 이상적으로 DBS와 같은 전기 치료는 시간이 지남에 병적 인 행동과 상호 작용하는 방법의 연구에 적합합니다. 우리가 설명하는 절차는 다른 환경에서 우발 메스 암페타민 사용에 대한 하나의 환경에서 DBS의 효과를 검사합니다. 우리의 IV의 필로폰 자기 administ의 세 가지 주요 단계가 있습니다배급 패러다임 : 긴 액세스 세션 동안 신속한 수집 및 약물 섭취의 상승 1) 유도, 이후 짧은 액세스 세션 동안 약물 섭취의 안정, 높은 비율의 2) 유지 관리 및 약물 복용의 전면 적재 패턴의 3) 개발. 비용 효율적이고 이상적 정신 자극제를 사용하여 설치류 헤드 캡의 잠재적으로 제한 수명 주어진 DBS의 효과를 테스트하기에 적합한 양이다 실험 당 12 래트 -이 패러다임은 10 2-3주 시간 내에 달성 될 수있다. 긴 19,30,31 액세스의 기간을 포함 다른 패러다임 등이 절차는 상당히 물질 사용 장애의 일부 측면을 시뮬레이션; 그것은 레크리에이션 사용 19,30 대 인간의 의존성의 중요한 측면이다 초기 세션 &quot;약물 로딩,&quot;로 약물을 얻기 위해 사용과 높은 동기 부여의 두 상승을 보여줍니다. IV의 필로폰 긴 액세스 노출이 설치류는인지 적자 (32)을 보여, 약물 치료 33, 약물 동태 학 (34)과 신경 화학적으로 별개의 응답은 짧은 액세스 노출 설치류보다 만성 메스 암페타민 사용 장애로 고통 인간에게 더 유사하다 (35)을 변경합니다. 마찬가지로 우리의 깊은 뇌 자극 절차의 세 가지 주요 단계가 있습니다 : 하나 또는 두 개의 &quot;모의&quot;세션의 머리 밧줄 연결을 포함 DBS 환경, 1) 요법 이니, 2) 매일, 상용 시스템을 사용하여 활성 자극의 간헐적 인 배달, 3) DBS의 분리 및 약물 설정 이후에 전송. 이 패러다임은 다소 전통적인 연속 DBS보다 TMS 같은 비 침습적 치료의 과정을 모방하도록 설계된다. 완전 이식, 일반적인 운동 장애 3에 사용되는 것과 같은 프로그램 DBS 시스템은 여러 가지 전술 한 이유로 정신 자극제 의존을 앓고있는 환자의 변두리에 가능한 것입니다. Intermitten더 나은이 환자 인구에 적용 할 수있다 TMS 같은 위험도가 높은 수술과 사후를 포함하지 않는 전기 치료 전략을, t. 우리가 기술 한 방법은 연구자가 개발하고 제한된 시간 내에 약물 환경 외부에서 전달되는 동안 마약 관련 동작을 수정할 수 있습니다 치료 전략을 구체화 할 수 있습니다. 축적 증거가 특정 신경 생리 학적 결손 (23) 후에 모방 또는 치료 중단 후 전신 약물 (36)을 발휘 몇 주 동안 정신 및 약물 관련 행동에 긍정적 인 효과를 오래 지속과 결합 과도 두개 전기 자극. 초기 우수한 수술 기법과 강렬한 약물 사용 중에 여러 수술 사이트의 지속적인 관리를위한 요구 사항은이 방법의 주요 제한 사항입니다. IV 카테터 또는 DBS 전극 중 하나가 비 작동 및 / 또는 감염 될 경우, 쥐해야연구를 종료합니다. 엄격한 무균 기술에서 경정맥 카테터 및 두개강 ​​내 전극 게재 위치를 가장 독립적으로이 절차를 시작하기 전에 경험이 풍부한 연구자에서 배운됩니다. . 자극 파형, 펄스 폭, 주파수, 진폭), 2) 다른 잠재적 인 치료 뇌 타겟 (예 - - 핵 중격 의지 1) 다른 자극 파라미터 (예 :.이 절차의 검토를 포함하여 여러 변형 및 미래 연구, 의무가있다 코어, 내측 전두엽 피질, 중뇌, habenula), 3) 다른 DBS 전달 패턴 (예를 들어, -. 매일 DBS 배달, 주간 DBS 배달, DBS 이전에 가장 흥미로운 아마도 조작 적 세션, DBS 인수 전), 그리고, 다양한 간격으로, 4) 짧은 기간 DBS의 조합과 선택적 경로의 optogenetic 자극을 모방 행동 수정 (36)을 지속 발휘 제약 에이전트.

필로폰 인해 시냅스 모노 아민의 급성 증가, 특히 도파민에 강렬하고 장기간의 행복감을 생산하는 정신 자극제입니다. 필로폰 의존은 전 세계적으로 약 25-34000000 사용자와 전혀 입증 된 치료 1, 2와 전염병의 건강 문제입니다. 메탐페타민에 대한 의존성 신규 한 치료 전략의 개발이 상당히 요구되고있다. 깊은 뇌 자극 (DBS)은 두뇌 &quot;심장 박동&quot;파킨슨 병, 근육 긴장 이상, 그리고 3 태성 진전 비롯한 특정 질환에서 발생하는 신경 세포 파괴 소성 패턴을 정상화를 사용하여 신경 외과 절차이다. 최근 인간의 경우 보고서는 DBS는 알코올 및 약물 의존에 대한 효과적인 치료가 될 수 있지만, 정신 자극제에 대한 임상 증거 (예 :., 코카인, 필로폰)이 4-8을 제한하는 것이 좋습니다. 연속 깊은 뇌 자극이 currentl 그대로Y는 연습 환자와 그 / 그녀의 가족에서 예외적 인 협력이 필요합니다. 꼼꼼한 상처 치료 및 개인 위생에도 결과 균혈증과 정맥 약물을 사용하지 않는 환자에서 감염에 취약 기본 맥박 조정기 하드웨어를 보호해야합니다. DBS 장치의 정기적 추적 시스템의 개방 루프 설계 주어진 필요가있다; 경험이 풍부한 의사 일상 클리닉 약속 3시 대상의 증상을 감소시키는 현대 DBS의 설정을 변경합니다. 이 치료의 패러다임은 그들의 도전 정신 사회적 상황에 코카인과 암페타민 사용자로 제한됩니다. 여러 설치류 연구는 치료가 약물 사용 환경 9-11에서 코카인 자기 관리 절차 중에 연속적으로 전달 될 ​​때 DBS의 효과를 검토하여이 비현실적 패러다임을 모방했다. 두개 같이 내주 하드웨어를 필요로하지 않는 불연속 기법 비 침습적자기 자극 (TMS)은, 물질 사용 장애 (12)의 치료를위한 더 나은 옵션이 될 수 있습니다. TMS는 비 침습적 하루 동안 특정 뇌 대상 전기 필드, 간헐적 인 치료를 생성하는 외부 headcoil를 사용하여 제공됩니다. H 코일 또는 &quot;깊은&quot;은 TMS가 잠재적 인 사용을 확대 13,14, 피질 부위에 추가로, 깊은 뇌 자극 구조가되도록 최근 출현. 두 치료법은 기본 약물 사용의 경우보다 다른 환경에서 세션 동안 연속적으로 일련의 전달 및 약물 의존 13,15-17 인간과 쥐 실험 모두에서 약속을 보여 주었다. 그들이 폭력적이거나 산만 한 행동 (18)을 체험 할 수있는 경우 필로폰 의존 환자를 치료하는 창 가능성이 거리 binges 동안하지, 같은 법원이 의무적으로 재활 등의 금주 기간 동안있을 것입니다. 따라서,이 문서의 목적은 일시적이다 전기 자극의 전달을 설명하는 것입니다공간적으로 더 밀접 IV의 암페타민 의존의 치료를위한 인간에서 무엇이 가능한지에 근사 약물 사용 환경으로부터 분리한다.

<table><tbody><tr><td>Rodent operant chambers</td><td>Med Associates, Inc</td><td>ENV-008CT</td><td>Med Associates Inc. PO Box 319 St. Albans, Vermont 05478 USA Phone: (802) 527-2343</td></tr><tr><td>Kopf Small Animal Stereotaxic Instrument with Digital Display Console</td><td>Kopf Instruments</td><td>Model 940</td><td>Kopf Phone: 1-877-352-3275 Fax: 1-818-352-3275 Email: sales@kopfinstruments.net</td></tr><tr><td>Z-Series 3-DSP Bioamp Processor</td><td>Tucker Davis Technologies</td><td>RZ5D</td><td>Tucker-Davis Technologies&amp;nbsp;11930 Research Circle Alachua, FL 32615&amp;nbsp;USA Ph: 386-462-9622&amp;nbsp;www.tdt.com</td></tr><tr><td>Z-Series 32-Channel Stimulator</td><td>Tucker Davis Technologies</td><td>IZ2-32</td><td>Software is accompanied by a manual that discusses how to program experiments using the OpenEx platform, which can be accessed here: http://www.tdt.com/files/manuals/OpenEx_User_Guide.pdf</td></tr><tr><td>48 Volt LI-ION Battery Pack for IZ2 Stimulator</td><td>Tucker Davis Technologies</td><td>LZ48-200</td><td></td></tr><tr><td>32-Channel Splitter Box for PZ5</td><td>Tucker Davis Technologies</td><td>S-BOX_PZ5</td><td></td></tr><tr><td>OpenEx Ext Software Package for Multi-Channel Neural Recording</td><td>Tucker Davis Technologies</td><td>OpenEx</td><td></td></tr><tr><td>Platinum-iridium stimulating electrodes</td><td>Plastics One Inc</td><td>MS303/8-B/SPC ELECT PT 2C TW .005&quot;</td><td>Plastics One Inc P.O.Box 21465, S.W. Roanoke, VA 24018, PH 540-772-7950</td></tr><tr><td>2-channel cables between stimulator and commutator</td><td>Plastics One Inc</td><td>305-441/2 W/ Spring</td><td></td></tr><tr><td>2-channel cables between commutator and electrode pedestal</td><td>Plastics One Inc</td><td>305-305 W/ Spring</td><td></td></tr><tr><td>4-channel commutators</td><td>Plastics One Inc</td><td>SL2+2C and SL2+SC/SB</td><td></td></tr></tbody></table>

a general method for evaluating deep brain stimulation effects on intravenous methamphetamine self-administration

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

IV의 경정맥 카테터 및 두개 내 DBS 전극의 배치에 따라, 설치류가 성공적으로 짧은 회복 기간 후 자기 관리] 4의 필로폰을 훈련 할 수있다. 쥐를 획득하고 확장 된 액세스 2 일 이후 필로폰 자기 관리를 확대 할 3은 그림 4 일에 의해 세션 당 168 ± 12 주입의 평균 약물. 1) 필로폰 독성 및 영구, 장기간 액세스 할 수있는 심각한 행동 변화를 방지하고 2) 그 응답의 상대적으로 안정적인 속도를 설정하기 위해 다양한 조작 할 수 있습니다 쥐 다음 두 가지 이유에 대한 조작 적 훈련을 매일 2 시간 일정으로 이동 치료 적 개입. 그림 4는 두 번째 주에 걸쳐 짧은 액세스 세션 당 총 주입의 평균 수는 75 ± 8임을 보여줍니다 일반적으로 10 % 이하로 일상을 변화한다. 그림 5는 쥐 (STABLE)를 보여줍니다OP 일에 비해 훈련 6 일째에 의한 섭취 &quot;프런트 로딩」패턴의 출현에 의해 나타낸 바와 같이 약물을 취할 증가 동기 1.이 개발되면, 효과는 크게 후속 세션 동안 유지된다 (데이터는 미도시) . 그림 6은 양자 DBS는 가짜 자극 군에 비해 3 ~ 5의 일에 대한 조작 적 IV의 필로폰 자기 관리의 현저한 감소의 결과 비 약물 환경에서 전달되는 것을 알 수있다. (- 8.5, ML은 2.4 ± AP + 1.6, DV)의 핵은 쉘은 브레 그마를 기준으로 좌표를 다음 정위를 사용하여 약물 consummatory 동작을 8 년에 알려진 참여를 목표로하는 소정했다 중격 의지. 자극 파라미터 및 지속 시간은 느슨하게 정신과 8,20,21 질병의 치료 용 DBS와 이전 경험에 기초하여 게시 되었으나 실험자의 요구에 따라 조정될 수있다. 오차 막대는 온건하고 모든 일 것이란 있습니다명확한 치료 효과의 평가에도 불구하고, 행동에서 볼 수있는 응답의 범위를 나타내는 의미 CH. 실험 당 쥐의 수를 늘리면이 자연의 변화를 보상 할 수 있습니다. 11 동물은 초기 실험에 사용 하였다. 하나의 동물에 의한 발작에 수유 수술 후, 하나의 동물이 제외 된 대한 안락사하고, 하나의 동물 (8) 동물의 총을 우리에게 남겨 인해 DBS 전극 고장 제외되었다 (; N = 4 활성 DBS를 N = 4 샴). 성공적인 완료를 허용 각 실험 (12) 쥐 - 일반적으로 약 10부터 시작. <img alt="그림 1" src="/files/ftp_upload/53266/53266fig1.jpg" /> 그림 1. 비주얼 프로그래밍 언어. 조사는 여러 애니에 뇌 자극을 제공 할 수있는 프로그램을 설계, 여기의 예처럼, 비주얼 프로그래밍 언어를 사용LS 동시에 사용자가 입력 매개 변수에. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53266/53266fig1large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 2" src="/files/ftp_upload/53266/53266fig2.jpg" /> 도 2 카메라 제어판. 실험의 개시에 앞서, 조사관 시각적 컨트롤 패널의 왼쪽에 원하는 주파수, 펄스 폭과 진폭을 지정한다. 여기에 자극 매개 변수는 다음과 같습니다 현재 강도 200 μA; 펄스는 61 밀리 폭; 펄스 주파수 130 Hz에서. 자극이 활성 전류 전달을위한 파형이 오른쪽에 표시됩니다 시작되면. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53266/53266fig2large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> IV 필로폰 자기 관리 그림 3. 취득. 응답 전체 조건화는 (360 분) 데이터는 반복 측정으로 정의 매일 세션과 반복 - 측정 ANOVA를 이용하여 분석 하였다. 페이지를 한 모든 분석은 &lt;0.05으로 유의하다고 하였다. 데이터는 평균 ± 표준 오차이다. 조작 적 훈련 첫 4 일 동안 매일 6 시간 조작 적 세션 동안 총 필로폰 주입. + P &lt;0.05 세션 1에 비교 2. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53266/53266fig3large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 4" src="/files/ftp_upload/53266/53266fig4.jpg" /> 그림 4.IV 필로폰 자기 관리의 유지 보수. 총 조작 적 응답 (120 분) 데이터는 반복 측정으로 정의 매일 세션과 반복 - 측정 ANOVA를 이용하여 분석 하였다. 페이지를 한 모든 분석은 &lt;0.05으로 유의하다고 하였다. 데이터는 평균 ± 표준 오차이다. 안정된하지만 강렬한 약물 복용 행동을 보여주는 조작 적 훈련, 둘째 주에 걸쳐 매일 2 시간의 조작 적 세션 동안 총 필로폰 주입. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53266/53266fig4large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 5" src="/files/ftp_upload/53266/53266fig5.jpg" /> 그림 동기 부여의 5 개발은 약을 복용합니다. 조작 적 첫 번째 시간 동안 매 15 분을 합계 한이 응답하고 데이터를 분석 하였다 사용하여 반복-날ANOVA는 반복 측정으로 정의 된 각 15 분 사분면으로 asures. 페이지를 한 모든 분석은 &lt;0.05으로 유의하다고 하였다. 데이터는 평균 ± 표준 오차이다. &quot;프런트 로딩&quot;패턴은 조작 적 훈련의 1 일에 존재하는 것이 아니라 약을 복용하는 강한 의욕을 나타내는 두 번째 주에 의해 개발. + P &lt;0.05에 비해 60 분에 비해 45 ~ 60 분, + + + P &lt;0.05에 비해 30, 45, 60 분, + + P &lt;0.05. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53266/53266fig5large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 6" src="/files/ftp_upload/53266/53266fig6.jpg" /> 그림 6. IV 필로폰 자기 관리에 DBS 효과. 제 시간에 응답 총 조건화는 (60 분) 데이터는 betwe와 혼합 ANOVA를 이용하여 분석 하였다치료의 대상 변수 (가짜 대 DBS) 매일 세션의 반복 측정 갖추고 있습니다. 페이지를 한 모든 분석은 &lt;0.05으로 유의하다고 하였다. 데이터는 평균 ± 표준 오차이다. 양자 미리 조건화 깊은 뇌 자극이 크게 치료 일 3, 4에 대응 조건화의 제 60 분에 걸쳐 주입 메탐페타민의 수를 감소하고, 모의 그룹과 기준선 응답에 비해 7 + P &lt;0.05. 종료 매일 치료 후베이스 라인 수준으로 돌아 응답. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53266/53266fig6large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a>

Watch this Scientific Journal Video about A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration at JoVE.com

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

정맥 필로폰 자기 관리에 깊은 뇌 자극의 효과를 평가하기위한 일반적인 방법

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people.  There is a need ...

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15.1K 조회수.  Louisiana State University. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

비디오: A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Novel Apparatus and Method for Drug Reinforcement

Animal models of reinforcement have proven to be useful for understanding the neurobiological mechanisms underlying drug addiction. Operant drug self-administration and conditioned place preference (CPP) procedures are expansively used in animal research to model various components of drug reinforcement, consumption, and addiction in humans. For this study, we used a novel approach to studying drug reinforcement in rats by combining traditional CPP and self-administration methodologies. We assembled an apparatus using two Med Associate operant chambers, sensory stimuli, and a Plexiglas-constructed neutral zone. These modifications allowed our experiments to encompass motivational aspects of drug intake through self-administration and drug-free assessment of drug/cue conditioning strength with the CPP test. In our experiments, rats self-administered cocaine (0.75 mg/kg/inj, i.v.) during either four (e.g., the "short-term") or eight (e.g., the "long-term") alternating-day sessions in an operant environment containing distinctive sensory cues (e.g., olfactory and visual). On the alternate days, in the other (differently-cued) operant environment, saline was available for self-infusion (0.1 ml, i.v.). Twenty-four hours after the last self-administration/cue-pairing session, a CPP test was conducted. Consistent with typical CPP findings, there was a significant preference for the chamber associated with cocaine self-administration. In addition, in animals undergoing the long-term experiment, a significant positive correlation between CPP magnitude and the number of cocaine-reinforced lever responses. In conclusion, this apparatus and approach is time and cost effective, can be used to examine a wide array of topics pertaining to drug abuse, and provides more flexibility in experimental design than CPP or self-administration methods alone.

Operant drug self-administration and conditioned place preference (CPP) procedures are expansively used in research to model various components of drug reinforcement, consumption, and addiction in humans. In this report, we combined traditional CPP and self-administration methods as a novel approach to studying drug reinforcement and addiction in rats.

약물 보강 소설 장치 및 방법

Animal models of reinforcement have proven to be useful for understanding the neurobiological mechanisms underlying drug addiction.  Operant drug ...

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A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

계단 및 실린더 테스트 : 소설 접근은 Hemiparkinsonian 쥐에 깊은 뇌 자극 효과의 모터 결과를 평가하는

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

행동분석학

Methods for Intravenous Self Administration in a Mouse Model

Animal models have been developed to study the reinforcing effects of drugs, including the intravenous self-administration (IVSA) paradigm. The advantages of using an IVSA paradigm to study the reinforcing properties of drugs of abuse such as cocaine include the fact that the drug is self-administered instead of experimenter-administered, the schedule of reinforcement can be altered, and accurate measurement of the quantities of drug consumed as well as the timing and pattern of IV injections can be obtained. Furthermore, the intravenous route of administration avoids potential confounds related to first pass metabolism or taste, and produces rapid increases in blood and brain drug levels. As outlined in this video, intravenous self-administration can be obtained without prior food restriction or prior drug training following careful catheter placement during surgery and meticulous daily catheter flushing and maintenance. Experimental procedures outlined in this paper include a description of animal housing and acclimation methods, operant training using sweetened milk solutions, and catheter implantation surgery.

The intravenous self-administration (IVSA) paradigm is considered to be the gold standard in examining the reinforcing properties of drugs of abuse in rodents. This manuscript outlines the experimental procedures and surgical techniques necessary to obtain reliable IVSA data. In particular, meticulous catheter implantation and maintenance are highlighted.

마우스 모델에서 정맥 주사 자기 관리를위한 방법

Animal models have been developed to study the reinforcing effects of drugs, including the intravenous self-administration (IVSA) paradigm. The advantages ...

Microdialysis of Ethanol During Operant Ethanol Self-administration and Ethanol Determination by Gas Chromatography

Operant self-administration methods are commonly used to study the behavioral and pharmacological effects of many drugs of abuse, including ethanol. However, ethanol is typically self-administered orally, rather than intravenously like many other drugs of abuse. The pharmacokinetics of orally administered drugs are more complex than intravenously administered drugs. Because understanding the relationship between the pharmacological and behavioral effects of ethanol requires knowledge of the time course of ethanol reaching the brain during and after drinking, we use in vivo microdialysis and gas chromatography with flame ionization detection to monitor brain dialysate ethanol concentrations over time. 
Combined microdialysis-behavioral experiments involve the use of several techniques. In this article, stereotaxic surgery, behavioral training and microdialysis, which can be adapted to test a multitude of self-administration and neurochemical centered hypotheses, are included only to illustrate how they relate to the subsequent phases of sample collection and dialysate ethanol analysis. Dialysate ethanol concentration analysis via gas chromatography with flame-ionization detection, which is specific to ethanol studies, is described in detail. Data produced by these methods reveal the pattern of ethanol reaching the brain during the self-administration procedure, and when paired with neurochemical analysis of the same dialysate samples, allows conclusions to be made regarding the pharmacological and behavioral effects of ethanol.

A method to determine the time course of ethanol concentration in the brains of rats during operant ethanol self-administration is described. Gas chromatography with flame ionization detection is used to quantify ethanol in the dialysate samples, because it has the sensitivity required for the small volumes that are generated.

가스 크로마토 그래피에 의한 operant 에탄올 자기 관리 및 에탄올 결정시 에탄올의 Microdialysis

Operant self-administration methods are commonly used to study the behavioral and pharmacological effects of many drugs of abuse, including ethanol.  ...

A Procedure for Implanting Organized Arrays of Microwires for Single-unit Recordings in Awake, Behaving Animals

In vivo electrophysiological recordings in the awake, behaving animal provide a powerful method for understanding neural signaling at the single-cell level. The technique allows experimenters to examine temporally and regionally specific firing patterns in order to correlate recorded action potentials with ongoing behavior. Moreover, single-unit recordings can be combined with a plethora of other techniques in order to produce comprehensive explanations of neural function. In this article, we describe the anesthesia and preparation for microwire implantation. Subsequently, we enumerate the necessary equipment and surgical steps to accurately insert a microwire array into a target structure. Lastly, we briefly describe the equipment used to record from each individual electrode in the array. The fixed microwire arrays described are well-suited for chronic implantation and allow for longitudinal recordings of neural data in almost any behavioral preparation. We discuss tracing electrode tracks to triangulate microwire positions as well as ways to combine microwire implantation with immunohistochemical techniques in order to increase the anatomical specificity of recorded results.

Implanting organized arrays of microwires for use in single-unit electrophysiological recordings presents a number of technical challenges.&#160;Methods for performing this technique and the equipment necessary are described.&#160;Also, the beneficial use of organized microwire arrays to record from distinct neural subregions with high spatial selectivity is discussed.

동물 행동하자, 깨어있는 단일 단위 레코딩을위한 Microwires의 조직 된 배열을 주입하기위한 절차

In vivo electrophysiological recordings in the awake, behaving animal provide a powerful method for understanding neural signaling at the single-cell ...

Deep Brain Stimulation with Simultaneous fMRI in Rodents

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal.&#160;Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS.

This protocol describes a standard method for simultaneous functional magnetic resonance imaging and deep brain stimulation in the rodent. The combined use of these experimental tools allows for the exploration of global downstream activity in response to electrical stimulation at virtually any brain target.

설치류에 동시 fMRI를 깊은 뇌 자극

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for ...

Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, dystonia or tremor. DBS is based on the delivery of electrical stimuli to specific deep anatomic structures of the central nervous system. However, the mechanisms underlying the effect of DBS remain enigmatic. This has led to an interest in investigating the impact of DBS in animal models, especially in rats. As DBS is a long-term therapy, research should be focused on molecular-genetic changes of neural circuits that occur several weeks after DBS. Long-term DBS in rats is challenging because the rats move around in their cage, which causes problems in keeping in place the wire leading from the head of the animal to the stimulator. Furthermore, target structures for stimulation in the rat brain are small and therefore electrodes cannot easily be placed at the required position. Thus, a set-up for long-lasting stimulation of rats using platinum/iridium electrodes with an impedance of about 1 M&#937; was developed for this study. An electrode with these specifications allows for not only adequate stimulation but also recording of deep brain structures to identify the target area for DBS. In our set-up, an electrode with a plug for the wire was embedded in dental cement with four anchoring screws secured onto the skull. The wire from the plug to the stimulator was protected by a stainless-steel spring. A swivel was connected to the circuit to prevent the wire from becoming tangled. Overall, this stimulation set-up offers a high degree of free mobility for the rat and enables the head plug, as well as the wire connection between the plug and the stimulator, to retain long-lasting strength.

A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.

미세 전극은 장기 깊은 뇌 자극 쥐의 Subthalamic 핵에 전극의 주입을 가이드

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, ...

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder

Cocaine use disorder (CUD) follows a trajectory of repetitive self-administration during which previously neutral stimuli gain incentive value. Cue reactivity, the sensitivity to cues previously linked with the drug-taking experience, plays a prominent role in human craving during abstinence. Cue reactivity can be assessed as the attentional orientation toward drug-associated cues that is measurable as appetitive approach behavior in both preclinical and human studies. Herein describes an assessment of cue reactivity in rats trained to self-administer cocaine. Cocaine self-administration is paired with the presentation of discrete cues that act as conditioned reinforcers (i.e., house light, stimulus light, infusion pump sounds). Following a period of abstinence, lever presses in the cocaine self-administration context accompanied by the discrete cues previously paired with cocaine infusion are measured as cue reactivity. This model is useful to explore neurobiological mechanisms underlying cue reactivity processes as well as to assess pharmacotherapies to suppress cue reactivity and therefore, modify relapse vulnerability. Advantages of the model include its translational relevance, and its face and predictive validities.&#160;The primary limitation of the model is that the cue reactivity task can only be performed infrequently and must only be used in short duration (e.g., 1 hour), otherwise rats will begin to extinguish the pairing of the discrete cues with the cocaine stimulus. The model is extendable to any positively reinforcing stimulus paired with discrete cues; though particularly applicable to drugs of abuse, this model may hold future applications in fields such as obesity, where palatable food rewards can act as positively reinforcing stimuli.

Cue reactivity is conceptualized as sensitivity to cues linked with drug-taking experiences that contribute to craving and relapse in abstinent humans. Cue reactivity is modeled in rats by measuring attentional orientation toward drug-associated cues that results in appetitive approach behavior in a cue reactivity test following self-administration and forced abstinence.

코카인 사용 장애의 쥐 모델에서 큐 반응성을 측정 하기 위한 프로토콜

Cocaine use disorder (CUD) follows a trajectory of repetitive self-administration during which previously neutral stimuli gain incentive value. Cue ...

An Invasive Method for the Activation of the Mouse Dentate Gyrus by High-frequency Stimulation

Electrical high-frequency stimulation (HFS), using implanted electrodes targeting various brain regions, has been proven as an effective treatment for various neurological and psychiatric disorders. HFS in the deep region of the brain, also named deep-brain stimulation (DBS), is becoming increasingly important in clinical trials. Recent progress in the field of high-frequency DBS (HF-DBS) surgery has begun to spread the possibility of utilizing this invasive technique to other situations, such as treatment for major depression disorder (MDD), obsessive-compulsive disorder (OCD), and so on. 
Despite these expanding indications, the underlying mechanisms of the beneficial effects of HF-DBS remain enigmatic. To address this question, one approach is to use implanted electrodes that sparsely activate distributed subpopulations of neurons by HFS. It has been reported that HFS in the anterior nucleus of the thalamus could be used for the treatment of refractory epilepsy in the clinic. The underlying mechanisms might be related to the increased neurogenesis and altered neuronal activity. Therefore, we are interested in exploring the physiological alterations by the detection of neuronal activity as well as neurogenesis in the mouse dentate gyrus (DG) before and after HFS treatment. 
In this manuscript, we describe methodologies for HFS to target the activation of the DG in mice, directly or indirectly and in an acute or chronic manner. In addition, we describe a detailed protocol for the preparation of brain slices for c-fos and Notch1 immunofluorescent staining to monitor the neuronal activity and signaling activation and for bromodeoxyuridine (BrdU) labeling to determine the neurogenesis after the HF-DBS induction. The activation of the neuronal activity and neurogenesis after the HF-DBS treatment provides direct neurobiological evidence and potential therapeutic benefits. Particularly, this methodology can be modified and applied to target other interested brain regions such as the basal ganglia and subthalamic regions for specific brain disorders in the clinic.

This protocol shows how to set up a reliable HFS method in mice. Neurons throughout the hippocampal dentate gyrus are electrically stimulated by HFS directly and indirectly in vivo. Neuronal activity and molecular signaling are examined by c-fos and Notch1 immunofluorescent staining, respectively; neurogenesis is quantified by bromodeoxyuridine labeling assay.

고주파 자극에 의해 마우스가 뇌의 활성화에 대 한 침략 적 방법

Electrical high-frequency stimulation (HFS), using implanted electrodes targeting various brain regions, has been proven as an effective treatment for ...

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry (CIS-FSCV) to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine

Phasic dopamine (DA) release from the ventral tegmental area (VTA) to the nucleus accumbens plays a pivotal role in reward processing and reinforcement learning. Understanding how the diverse neuronal inputs into the VTA control phasic DA release can provide a better picture of the circuitry that controls reward processing and reinforcement learning. Here, we describe a method that combines intra-VTA cannula infusions of pharmacological agonists and antagonists with stimulation-evoked phasic DA release (combined infusion and stimulation, or CIS) as measured by in vivo fast-scan cyclic voltammetry (FSCV). Using CIS-FSCV in anesthetized rats, a phasic DA response can be evoked by electrically stimulating the VTA with a bipolar electrode fitted with a cannula while recording in the nucleus accumbens core. Pharmacological agonists or antagonists can be infused directly at the stimulation site to investigate specific VTA receptors&#39; roles in driving phasic DA release. A major benefit of CIS-FSCV is that VTA receptor function can be studied in vivo, building on in vitro studies.

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry CIS-FSCV to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine

The goal of this protocol is to directly manipulate ventral tegmental area receptors to study their contribution to subsecond dopamine release.

빠른 스캔 순환 볼탐법 (CIS-FSCV)과 결합 된 주입 및 자극을 결합하여 Phasic 도파민의 복부 테자멘트 영역 수용체 조절을 평가합니다.

Phasic dopamine (DA) release from the ventral tegmental area (VTA) to the nucleus accumbens plays a pivotal role in reward processing and reinforcement ...