GABA_B(1A) receptors seem to play a critical role in fear generalization. Additionally, GABA_B(1a) knockout animals or animals given a GABA_B(1A) receptor antagonist generalize fear to a neutral context. Based on these results, we became interested in the role of GABA_B(1A) receptors in extinction learning.

The extinction of fear occurs when a conditioned stimulus previously paired with an aversive stimulus is repeatedly presented alone. This repeated presentation of the conditioned stimulus results in a decrease in the conditioned response. Following extinction learning, the renewal of fear sometimes occurs during testing in a different context

To determine the role of GABA_B(1A) receptors in extinction learning, we began by training GABA_B KO animals in Context A to five tone-shock pairings. Extinction occurred over two days in Context B. Then, animals were tested in each context for a freezing response to the tone. We found that animals lacking GABA_B receptors exhibited less freezing behavior during extinction than did wildtype animals.

To further test this effect, we replicated this study pharmacologically. C57 mice underwent extinction training in the same manner but received infusions of either vehicle of a GABA_B(1A) antagonist (CGP 36216) just prior to extinction or immediately after the completion of one day of extinction. The GABA­_B(1A) antagonist had a significant effect in enhancing extinction learning. We also observed greater extinction retention in the drug group. These results indicate that the inhibition of GABA_B(1A) receptors enhances the process of extinction learning.