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Updated: Jul 18, 2026

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Activation in extended amygdala corresponds to altered hedonic processing during protracted morphine withdrawal
Glenda C Harris1, Gary Aston-Jones
1Department of Psychiatry, University of Pennsylvania, Translational Research Labs/3403, 125 S 31st Street, Philadelphia, PA 19104, United States.
Morphine withdrawal in rats reduces food preference by altering brain activity in reward and stress pathways. This suggests heightened stress responses impact natural reward seeking during protracted abstinence.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Addiction Research
Background:
- Protracted morphine abstinence in rats leads to reduced conditioned place preferences (CPP) for food.
- Understanding the neural underpinnings of this altered reward behavior is crucial for addiction research.
Purpose of the Study:
- To identify brain regions associated with altered reward processing during protracted morphine abstinence.
- To investigate neural activation patterns (Fos expression) in response to food-associated environments in abstinent versus non-dependent rats.
Main Methods:
- Examined Fos-like protein expression as a marker of neural activation.
- Compared Fos expression in anterior cingulate cortex (Cg), basolateral amygdala (BLA), ventral lateral bed nucleus of the stria terminalis (VL-BNST), central nucleus of the amygdala (CE), and nucleus tractus solitarius (NTS) in morphine-abstinent and non-dependent rats.
- Correlated Fos expression with conditioned place preference behavior.
Main Results:
- Elevated Fos expression in the anterior cingulate cortex (Cg) and basolateral amygdala (BLA) correlated positively with food preference across all groups.
- Morphine-abstinent rats showed significantly elevated Fos expression in stress-related areas (VL-BNST, CE, NTS).
- In abstinent rats, Fos expression in these stress-related areas negatively correlated with food preference.
Conclusions:
- Heightened activity in stress-related brain areas, including the extended amygdala and its noradrenergic inputs, may underlie decreased preference for natural rewards during protracted morphine withdrawal.
- Altered hedonic processing during withdrawal involves complex interactions between reward and stress circuitry.
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