Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats

Matthew T. Rich; Yanhua H. Huang; Mary  M. Torregrossa

doi:10.3791/63185

JoVE Journal
Neuroscience

A subscription to JoVE is required to view this content. Sign in or start your free trial.

JoVE Journal Neuroscience

Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats

광유전학을 사용하여 신경 가소성을 역전시키고 쥐에서 코카인 추구를 억제

Full Text

3,082 Views

09:43 min

October 5, 2021

DOI: 10.3791/63185-v

Matthew T. Rich^1,2, Yanhua H. Huang¹, Mary M. Torregrossa¹

¹Department of Psychiatry,University of Pittsburgh, ²Department of Psychiatry,Rutgers University

Please note that some of the translations on this page are AI generated. Click here for the English version.

Overview

This study outlines a procedure to optogenetically reverse cocaine-induced plasticity in thalamo-amygdala circuits in rats. The approach uses sustained low-frequency optical stimulation to induce long-term depression (LTD), thereby attenuating cue-motivated drug-seeking behavior in cocaine-experienced rats.

Key Study Components

Area of Science

Neuroscience
Behavioral Biology
Optogenetics

Background

This protocol utilizes optogenetic techniques to manipulate synaptic activity.
A preclinical model of substance abuse in cocaine-experienced rats is employed.
The study addresses how neural circuits contribute to relapse behavior.
Long-lasting effects of synaptic alterations on drug-seeking behaviors are investigated.

Purpose of Study

To reverse cocaine-induced neural plasticity in a specific circuit.
To understand the role of synaptic changes in promoting relapse.
To enable circuit-specific manipulations in awake animals.

Methods Used

The main platform involves in vivo optogenetic stimulation in a rat model.
The biological model consists of cocaine-experienced rats and focuses on thalamo-amygdala circuits.
This method includes surgical protocols for adeno-associated viral injections and optic fiber implantation.
Critical steps include drug self-administration training, extinction sessions, and optogenetic stimulation procedures.

Main Results

Optogenetic induction of LTD resulted in diminished cue-motivated drug-seeking behavior in rats.
The manipulation of synaptic activity led to long-term inhibitory effects relevant to relapse.
Behavioral assessments showed significant changes after the optogenetic intervention.

Conclusions

The study demonstrates a method for precisely manipulating behaviors associated with drug relapse.
This approach provides insights into the underlying mechanisms of neuroplasticity related to addiction.
Implications for developing targeted interventions in substance use disorders are discussed.

Frequently Asked Questions

What is the advantage of using optogenetics in this study?

Optogenetics allows for precise control of neural activity in specific circuits, enabling researchers to explore causal relationships between neural plasticity and behavior.

How is cocaine exposure implemented in the rat model?

Cocaine self-administration is conducted in operant chambers, allowing rats to lever press for cocaine infusions over a training period.

What outcomes can be measured following the optogenetic manipulation?

Behavioral outcomes include changes in cue-motivated drug-seeking behaviors, measured through lever pressing in operant conditioning chambers.

Can this method be applied to other substance use disorders?

Yes, the method can be adapted to study neuroplasticity and behavior in various circuits associated with different substances.

What limitations should researchers consider with this protocol?

Limitations include species-specific responses and potential variability in individual animal behavior that may affect reproducibility.

여기에 설명 된 방법은 쥐의 행동 관련 회로에서 코카인으로 유도 된 가소성을 광학 유전 학적으로 역전시키는 데 사용되는 절차를 설명합니다. 시상 편도체 시냅스의 지속적인 저주파 광 자극은 장기 우울증 (LTD)을 유도합니다. 코카인 경험이 있는 쥐에서 생체내 광유전학적으로 유도된 LTD는 단서-동기 약물 탐색의 후속 감쇠를 초래하였다.

이 프로토콜은 광유전학 기술의 새로운 발전과 약물 남용의 전임상 모델을 사용하여 재발을 촉진하는 신경 회로의 가소성을 역전시키기 때문에 중요합니다. 이 기술의 주요 장점은 깨어있는 동물에서 시냅스 활동의 회로 특이 적 조작을 허용한다는 것인데, 이는 미래의 단서 동기 부여 코카인 추구 행동에 오래 지속되는 억제 효과가 있습니다. 이 방법은 행동적으로 관련된 신경 가소성을 구체적으로 조작하기 위해 다른 많은 시스템과 회로에서 활용 될 수 있습니다.

26게이지 스테인리스 스틸 주입 캐뉼러를 1마이크로리터의 농축 AAV 용액으로 채워진 해밀턴 주사기에 연결하여 수술 준비를 시작합니다. 동물을 마취 한 후 수술 부위를 면도하고 텍스트 원고에 설명 된대로 건조를 방지하기 위해 눈을 윤활하십시오. 다음으로, 진통제 인 카프로 펜의 체중을 등 상부의 피부를 통해 피하 주사하고, 허리의 피부를 통해 5 밀리리터의 젖산 링거 용액을 피하 주사한다.

View the full transcript and gain access to thousands of scientific videos