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A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Precipitated and conditioned withdrawal in morphine-treated rats.
Ginger L Becker1, Lisa R Gerak, Jun-Xu Li
1Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, Mail Code 7764, San Antonio, TX 78229, USA.
Environmental cues paired with opioid withdrawal can trigger similar effects, potentially leading to relapse. This study found conditioned withdrawal develops quickly and is amplified by repeated exposure and longer morphine treatment, suggesting potential therapeutic targets.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Environmental stimuli associated with opioid withdrawal can elicit withdrawal-like effects.
- These conditioned withdrawal responses may contribute to relapse in individuals with opioid use disorder.
Purpose of the Study:
- To compare precipitated and conditioned withdrawal responses in rats.
- To investigate the modulatory effects of clonidine and morphine on these withdrawal phenomena.
Main Methods:
- Rats treated with morphine received naloxone (precipitated withdrawal) in a novel environment (conditioned stimuli [CS]) or without the CS.
- Withdrawal signs and body weight changes were measured.
- The influence of prior physical dependence, drug pairings, and concurrent or preceding administration of clonidine or morphine was assessed.
Main Results:
- Naloxone induced withdrawal signs in morphine-dependent rats.
- The CS alone elicited naloxone-like effects, indicating conditioned withdrawal, which increased with more naloxone/CS pairings and longer morphine exposure.
- Physical dependence history did not alter conditioned withdrawal, but precipitated withdrawal was higher in dependent rats.
- Clonidine partially reduced precipitated withdrawal but not conditioned withdrawal.
- Morphine administration before CS exposure fully attenuated conditioned withdrawal, while clonidine had a partial effect.
Conclusions:
- Conditioned withdrawal develops rapidly and intensifies with increased exposure and duration of opioid treatment.
- A history of physical dependence does not enhance conditioned withdrawal.
- Pharmacological modulation of conditioned withdrawal, particularly with agents like morphine, shows promise for preventing relapse in opioid use disorder.
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