Source Paper
Propranolol Administration During Morphine Addiction Attenuates Reinstatement of Drug-Aversive Memories Caused by Exposure to Stressful Stimuli
Cánovas-Cabanes A, Teruel-Fernández FJ, Fernández-López L, Martínez-Laorden E, Navarro-Zaragoza J et al.
Pharmaceuticals (Basel) • 2025
Conditioned Place Aversion (CPA)
Objective: To assess aversive learning associated with opioid withdrawal using naloxone-induced conditioned place aversion
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Protocol Steps
Pre-test
Mice placed in central corridor and allowed to freely explore all compartments for 15 minutes, with time spent in each compartment recorded
View evidence from paper
“On day 0 (pre-test), mice were placed in the central corridor and allowed to freely explore the three compartments for 15 min”
Drug administration
Morphine administered intraperitoneally in escalating doses over 4 days, or saline for control animals
View evidence from paper
“From days 1 to 4, mice were injected with morphine or saline as described previously”
Conditioning
On day 4, naloxone administered 90 minutes after final morphine injection, then animals confined to one conditioning chamber for 15 minutes
View evidence from paper
“On day 4, 90 min after the final morphine injection, naloxone (1 mg/kg, s.c.) was administered to precipitate withdrawal. Immediately following injection, animals were confined to one of the two conditioning chambers for 15 min”
Post-test
CPA expression evaluated on day 5 under drug-free conditions using same procedure as pre-test
View evidence from paper
“CPA expression was evaluated on day 5 under drug-free conditions by using the same procedure as in the pre-test”
Extinction
Daily sessions for 20-25 days where mice freely access all chambers for 15 minutes until extinction criteria met
View evidence from paper
“Extinction sessions began 24 h after the CPA post-test and were conducted daily for 20–25 days until extinction criteria were met”
Reinstatement test
One day after extinction, mice exposed to stressors then allowed free access to all compartments for 15 minutes in different room
View evidence from paper
“reinstatement of naloxone-induced CPA was evaluated one day after extinction by exposing mice to either an acute social defeat or a physical stressor”