Extinction learning of rewards in the rat: Is there a role for CB1 receptors?

Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 2120, USA.
Psychopharmacology (Impact Factor: 3.88). 04/2011; 217(2):189-97. DOI: 10.1007/s00213-011-2275-7
Source: PubMed


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.
The aim of this study was to evaluate the role of endocannabinoids at different stages of extinction learning.
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.
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).
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.

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    • "Extinction of conditioned behavior is thought to be a process of new and active learning [4] [6] [10] [25]. CaMKII is well known as an important molecule in the mechanisms of learning and memory [8] [18] [19] [27] and the NAc is found to be involved in the extinction of conditioned behavior [11] [26]. "
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    ABSTRACT: The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) may be a core component in the common molecular pathways for drug addiction. Moreover, studies using animal models of drug addiction have demonstrated that changing CaMKII activity or expression influences animals' responses to the drugs of abuse. Here, we explored the roles of CaMKII in the nucleus accumbens (NAc) shell in the extinction and reinstatement of morphine-seeking behavior. Rats were trained to obtain intravenous morphine infusions through poking hole on a fixed-ratio one schedule. Selective CaMKII inhibitor myristoylated autocamtide-2-inhibitory peptide (myr-AIP) was injected into the NAc shell of rats after the acquisition of morphine self-administration (SA) or before the reinstatement test. The results demonstrated that injection of myr-AIP after acquisition of morphine SA did not influence morphine-seeking in the following extinction days and the number of days spent for reaching extinction criterion. However, pretreatment with myr-AIP before the reinstatement test blocked the reinstatement of morphine-seeking behavior induced by morphine-priming. Our results strongly indicate that CaMKII activity in the NAc shell is essential to the relapse to morphine-seeking.
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    • "Despite the remarkable effect on reinstatement, consensus is emerging in the literature on the lack of effect of (endo)cannabinoids on extinction of learned appetitively motivated tasks (Hernandez and Cheer, 2011). On the other hand, endocannabinoid mechanisms are strongly engaged in extinction of negatively motivated behavior (Marsicano et al., 2002; Lutz, 2007). "
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