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The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific
Floride Niyuhire1, Stephen A Varvel, Andrew J Thorpe
1Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
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.
Insights
The CB(1) receptor antagonist rimonabant impairs extinction of fear-based memories but not food-rewarded learning. This suggests a specific role for CB(1) signaling in aversive memory extinction.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Pharmacology
Background:
- Cannabinoid receptor type 1 (CB(1)) signaling disruption impairs extinction in fear-conditioned tasks.
- However, CB(1) receptor knockout mice show normal extinction in appetitive tasks.
Purpose of the Study:
- To investigate if rimonabant differentially affects extinction learning in fear-motivated versus food-motivated tasks.
- To clarify the role of CB(1) receptors in aversive versus appetitive memory extinction.
Main Methods:
- Mice were trained in conditioned freezing, passive avoidance (aversive), and operant conditioning (appetitive).
- Following training, reinforcers were withheld, and mice received vehicle or rimonabant before extinction sessions.
- Extinction rates were assessed in both task types.
Main Results:
- Rimonabant (3 mg/kg) significantly impaired extinction in conditioned freezing and passive avoidance tasks.
- Rimonabant did not affect extinction rates in the appetitive operant conditioning task.
- Rimonabant prevented the extinction burst (increased lever pressing) in the operant task.
Conclusions:
- CB(1) receptor signaling is crucial for the extinction of aversive memories.
- CB(1) receptors are not essential for extinguishing learned responses in appetitively motivated tasks.
- These findings highlight a specific role for CB(1) in processing fear-related extinction.
