RATIONALE: Drug addicts constantly relapse to drug seeking after recall of memories linked to the drug experience. It is believed that a successful application of therapies that block memory reconsolidation may end the continuous cycle of drug relapse. OBJECTIVES: The purpose of this study is to investigate whether modulation of the endocannabinoid system would impact the reconsolidation of opioid-related hedonic memories in rats previously paired to morphine context. METHODS: Male Wistar rats were trained to acquire a morphine-conditioned place preference (CPP). One week later, morphine-CPP memory was reactivated by a brief exposure to a drug-paired context. Immediately after the memory reactivation session, independent groups of morphine-trained rats received a single subcutaneous injection of different doses of cannabinoid CB1 receptor antagonist rimonabant, CB2-selective antagonist AM630, potent CB1/CB2 agonist WIN 55,212-2, inhibitor of enzyme fatty acid amide hydrolase URB597, or vehicle. Morphine-CPP was retested 1 and 2 weeks after reactivation. RESULTS: Blockade of CB1 (but not CB2) cannabinoid receptors impaired CPP reconsolidation of morphine-CPP at both tests 1 and 2 weeks post-reactivation, whereas direct activation of cannabinoid receptors did not produce significant effects on morphine-induced CPP. However, boosting endocannabinoid signaling by inhibition of anandamide metabolism promoted a transient CB1-dependent enhancement of the CPP.
RATIONALE: Drug addicts constantly relapse to drug seeking after recall of memories linked to the drug experience. It is believed that a successful application of therapies that block memory reconsolidation may end the continuous cycle of drug relapse. OBJECTIVES: The purpose of this study is to investigate whether modulation of the endocannabinoid system would impact the reconsolidation of opioid-related hedonic memories in rats previously paired to morphine context. METHODS: Male Wistar rats were trained to acquire a morphine-conditioned place preference (CPP). One week later, morphine-CPP memory was reactivated by a brief exposure to a drug-paired context. Immediately after the memory reactivation session, independent groups of morphine-trained rats received a single subcutaneous injection of different doses of cannabinoid CB1 receptor antagonist rimonabant, CB2-selective antagonist AM630, potent CB1/CB2 agonist WIN 55,212-2, inhibitor of enzyme fatty acid amide hydrolase URB597, or vehicle. Morphine-CPP was retested 1 and 2 weeks after reactivation. RESULTS: Blockade of CB1 (but not CB2) cannabinoid receptors impaired CPP reconsolidation of morphine-CPP at both tests 1 and 2 weeks post-reactivation, whereas direct activation of cannabinoid receptors did not produce significant effects on morphine-induced CPP. However, boosting endocannabinoid signaling by inhibition of anandamide metabolism promoted a transient CB1-dependent enhancement of the CPP.
Authors: Zuzana Justinova; Regina A Mangieri; Marco Bortolato; Svetlana I Chefer; Alexey G Mukhin; Jason R Clapper; Alvin R King; Godfrey H Redhi; Sevil Yasar; Daniele Piomelli; Steven R Goldberg Journal: Biol Psychiatry Date: 2008-09-23 Impact factor: 13.382
Authors: Jessica A Higginbotham; Rong Wang; Ben D Richardson; Hiroko Shiina; Shi Min Tan; Mark A Presker; David J Rossi; Rita A Fuchs Journal: J Neurosci Date: 2020-11-30 Impact factor: 6.167
Authors: David J Marcus; Angela N Henderson-Redmond; Maciej Gonek; Michael L Zee; Jill C Farnsworth; Randa A Amin; Mary-Jeanette Andrews; Brian J Davis; Ken Mackie; Daniel J Morgan Journal: PLoS One Date: 2017-04-20 Impact factor: 3.240