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Updated: Dec 25, 2025
04:11
A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
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Abstinence-dependent dissociable central amygdala microcircuits control drug craving
Marco Venniro1, Trinity I Russell2, Leslie A Ramsey2
1Behavioral Neuroscience Branch Intramural Research Program, National Institute on Drug Abuse (NIDA), NIH, Baltimore, MD 21224; venniro.marco@nih.gov yshaham@intra.nida.nih.gov.
Summary
Social abstinence prevents methamphetamine craving incubation by activating PKCδ neurons. Silencing PKCδ reversed this effect, while silencing SOM neurons reduced craving after forced abstinence, revealing distinct amygdala roles.
Area of Science:
- Neuroscience
- Addiction Research
- Molecular Biology
Background:
- Voluntary abstinence via social choice inhibits methamphetamine craving incubation in rats.
- This inhibition is linked to protein kinase-Cδ (PKCδ) neuron activation in the central amygdala lateral division (CeL).
- Forced abstinence, conversely, associates with somatostatin (SOM) neuron activation in CeL.
Purpose of the Study:
- To determine the causal roles of CeL PKCδ and SOM in the incubation of methamphetamine craving.
- To investigate the effects of manipulating PKCδ and SOM expression on drug seeking behavior and neural activation patterns.
Main Methods:
- Developed and validated short-hairpin RNAs (shRNAs) targeting PKCδ and SOM.
- Injected shPKCδ or shSOM into the CeL of rats, alongside control groups.
- Assessed relapse to methamphetamine seeking after varying abstinence periods (social choice vs. forced).
- Measured neural activation (Fos expression) in CeL and central amygdala medial division (CeM) post-abstinence.
Main Results:
- Silencing PKCδ in CeL reversed the inhibitory effect of social abstinence on craving.
- Silencing SOM in CeL reduced craving incubation following forced abstinence.
- Both manipulations altered Fos expression in CeL and CeM output neurons, indicating pathway involvement.
Conclusions:
- CeL PKCδ and SOM neurons play dissociable roles in regulating the incubation of methamphetamine craving.
- PKCδ is crucial for the inhibitory effects of voluntary abstinence.
- SOM is involved in the expression of craving after forced abstinence.
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