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Fear Conditioning
The fear conditioning learning and memory model is a method for evaluating trial compounds ability to reverse a drug-induced deficit in memory. Fear conditioning involves pairing a context and/or cue (conditioning stimuli, CS) to a shock (unconditioned stimulus) and later measuring the 'fear' response to the CS in the absence of the US. A defensive freezing or immobility response serves as a reliable measure of fear.

Contextual and auditory cue fear conditioning depend on different neural processes, whereas contextual conditioning is hippocampally driven and cued fear conditioning is not (Kim and Fanselow, 1992; Fendt and Fanselow, 1999). NMDA-type glutamate receptor antagonists and nicotinc cholinergic receptor antagonists cause amnestic effects in learning and memory tests such as fear conditioning (ref). These compounds are often used to produce deficits in these models. Several classes of drugs reverse learning and memory deficits in fear conditioning. These compounds include acetylcholinesterase inhibitors (Csernansky et al., 2005) and phosphodiesterase type 4 (PDE4) inhibitors (Gong et al. 2004).

 

 

Figure 1: Contextual Fear Conditioning Freezing Behavior in C57 Mice

 

             contextual freezing behavior fear conditioning mk801 rolipram

During the baseline training session on Day 1, there was minimal freezing across all groups.  There was a significant reduction in mean percent freezing in Veh-Veh and Veh-MK-801 treated animals (*p<0.05).  Animals treated with Rolipram had a small increase in baseline freezing. 

 

Contextual freezing was measured on Day 2.  Veh-Veh treated animals exhibited a marked increase in freezing behavior following fear conditioning training, indicating normal conditioning to the chamber context.  When the entire 8-minute test period is cosidered, MK-801 caused impariment of contextual memory, such that Veh-MK-801 animals had significantly reduced contextual freezing compared to Veh-Veh treated animals(#p<0.05) .

 

Figure 2: Cued Fear Conditioning Freezing Behavior in C57 Mice

 

           cued freezing fear conditioning mk801 rollipram

Cued freezing was measured on Day 3.  Veh-Veh treated animals exhibited a marked increase in freezing behavior in the presence of the auditory tone, indicating normal conditioning to the auditory cue.  When the entire 8-minute test period is considered, neither MK-801 nor Rolipram imparied cued memory, which is consistent with internal validation studies.

 

If you are interested in learning more about Fear Conditioning, please contact models@meliordiscovery.com to start the conversation.