Giovanni Hernandez1, Joseph F Cheer. 1. Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 2120, USA. giovannih@umaryland.edu
Abstract
RATIONALE: Endocannabinoids have been widely studied in the context of addiction and reward due to their role in reinstatement. However, little is known about the role of CB1 receptors during extinction learning of an appetitively motivated task. OBJECTIVE: The aim of this study was to evaluate the role of endocannabinoids at different stages of extinction learning. METHODS: Endocannabinoid signaling was disrupted by injecting the CB1 receptor antagonist rimonabant (0, 200, 300 μg/kg i.v.) during the acquisition or consolidation phases of learning. The rate of extinction and its half-life were analyzed, as well as food-seeking in a reward-induced reinstatement test. We further investigated the interaction between extinction and endocannabinoids in different groups of rats that received drug treatments but did not undergo extinction training (abstinence). In addition, the effects of rimonabant on cue retrieval were investigated in a cue-induced reinstatement test in which rimonabant (0, 300 μg/kg i.v.) was given immediately prior to the reinstatement session. RESULTS: Blockade of CB1 receptors during acquisition or consolidation of extinction learning had no effect on the rate extinction or its half-life and these pretreatments had no long term consequences on reward-seeking behavior. Furthermore, rats that underwent extinction training responded at lower levels than those that received the drug in the absence of extinction (p = 0.000, η (2) = 0.40). Rimonabant was effective in inhibiting behavior only if it was immediately given before a cue-induced reinstatement session (p = 0.000, η (2) = 0.92). CONCLUSION: The present results clarify and isolate the role of endocannabinoids in reinstatement as key mediators of cue retrieval, rather than orchestrators of extinction learning processes.
RATIONALE: Endocannabinoids have been widely studied in the context of addiction and reward due to their role in reinstatement. However, little is known about the role of CB1 receptors during extinction learning of an appetitively motivated task. OBJECTIVE: The aim of this study was to evaluate the role of endocannabinoids at different stages of extinction learning. METHODS: Endocannabinoid signaling was disrupted by injecting the CB1 receptor antagonist rimonabant (0, 200, 300 μg/kg i.v.) during the acquisition or consolidation phases of learning. The rate of extinction and its half-life were analyzed, as well as food-seeking in a reward-induced reinstatement test. We further investigated the interaction between extinction and endocannabinoids in different groups of rats that received drug treatments but did not undergo extinction training (abstinence). In addition, the effects of rimonabant on cue retrieval were investigated in a cue-induced reinstatement test in which rimonabant (0, 300 μg/kg i.v.) was given immediately prior to the reinstatement session. RESULTS: Blockade of CB1 receptors during acquisition or consolidation of extinction learning had no effect on the rate extinction or its half-life and these pretreatments had no long term consequences on reward-seeking behavior. Furthermore, rats that underwent extinction training responded at lower levels than those that received the drug in the absence of extinction (p = 0.000, η (2) = 0.40). Rimonabant was effective in inhibiting behavior only if it was immediately given before a cue-induced reinstatement session (p = 0.000, η (2) = 0.92). CONCLUSION: The present results clarify and isolate the role of endocannabinoids in reinstatement as key mediators of cue retrieval, rather than orchestrators of extinction learning processes.
Authors: Miriam Melis; Simona Perra; Anna Lisa Muntoni; Giuliano Pillolla; Beat Lutz; Giovanni Marsicano; Vincenzo Di Marzo; Gian Luigi Gessa; Marco Pistis Journal: J Neurosci Date: 2004-11-24 Impact factor: 6.167