The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific

Abstract

Rationale-Disruption of CB 1 receptor signaling through the use of CB 1 (-/-) mice or the CB 1 receptor antagonist rimonabant (SR141716) has been demonstrated to impair extinction of learned responses in conditioned fear and Morris water maze tasks. In contrast, CB 1 (-/-) mice exhibited normal extinction rates in an appetitively motivated operant conditioning task.Objectives-The purpose of this study was to test whether rimonabant would differentially disrupt extinction learning between fear-motivated and food-motivated tasks.Materials and methods-Separate groups of C57BL/6J mice were trained in two aversively motivated tasks, conditioned freezing and passive avoidance, and an appetitively motivated operant conditioning task at a fixed ratio (FR-5) schedule of food reinforcement. After acquisition, the respective reinforcers in each task were withheld, and an intraperitoneal injection of vehicle or rimonabant was given 30 min before each extinction session.Results-Rimonabant (3 mg/kg) treatment significantly disrupted extinction in both the conditioned freezing and passive avoidance tasks but failed to affect extinction rates in the operant conditioning task, whether using daily or weekly extinction sessions. Interestingly, rimonabant (3 mg/kg) prevented the significant increases in lever pressing (i.e., extinction burst) that occurred during the first extinction session of the operant conditioning task.Conclusions-These results support the hypothesis that the CB 1 receptor plays a vital role in the extinction of aversive memories but is not essential for extinction of learned responses in appetitively motivated tasks.

Cannabinoid Receptor Activation in the Basolateral Amygdala Blocks the Effects of Stress on the Conditioning and Extinction of Inhibitory Avoidance

“…Indeed, the importance of CB 1 receptors in the extinction of aversive memories has been substantiated by several groups in different behavioral paradigms using systemic administration. CB 1 receptor antagonists were found to impair extinction in fear-related (Marsicano et al, 2002;Suzuki et al, 2004;Chhatwal et al, 2005;Reich et al, 2008) and non-fear-related paradigms (Varvel and Lichtman, 2002), with no effect on appetitively motivated learning tasks (Hölter et al, 2005;Niyuhire et al, 2007;Harloe et al, 2008). Reich et al (2008) found that administrating AM251 enhances acquisition of freezing behavior and impairs extinction in trace and delay pavlovian fear conditioning.…”

A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats

“…The role of the endocannabinoid system in fear responding per se (i.e. in the absence of nociceptive tone) has been examined extensively and the weight of evidence suggests that endocannabinoid-CB 1 receptor signalling serves to facilitate and enhance the extinction of conditioned fear responding (for review see [15,48,79]), while genetic deletion or pharmacological blockade of the CB 1 receptor attenuates short-and long-term extinction of conditioned fear responding [14,18,25,39,44,48,52,59,62,70,76]. The results of the present study, however, suggest that in the presence of formalin-evoked nociceptive tone, increased endocannabinoid signalling in the vHip (as a consequence of URB597 administration) in fact serves to inhibit rather than enhance the short-term, within-trial extinction of fear responding.…”

Differential effects of cannabinoid receptor agonist on social discrimination and contextual fear in amygdala and hippocampus

“…CB1-deficient mice show impaired auditory fear extinction, with unaffected memory acquisition and consolidation (Marsicano et al 2002), whereas systemic and local cannabinoid receptor activation facilitate fear extinction (Chhatwal et al 2005;Pamplona et al , 2008Abush and Akirav 2010). So far, however, these findings on the involvement of CB1 receptors in extinction processes seem limited to aversive learning tasks, indicated by studies showing that CB1 receptors are not required in appetitive tasks (Hölter et al 2005;Niyuhire et al 2007). …”