Presynaptic GABA B receptor inhibition sex dependently enhances fear extinction and attenuates fear renewal

AbstractAnxiety and trauma-related disorders are highly prevalent worldwide, and  are associated with altered associative fear learning. Despite the effectiveness of exposure therapy, which aims to reduce associative fear responses, relapse rates remain high. This is due, in part, to the context specificity of exposure therapy, which is a form of extinction. Many studies show t hat fear relapses when mice are tested outside the extinction context, and this is known as fear renewal. Using Pavlovian fear conditioning and extinction, we can study the mechanisms underlying extinction and renewal. The aim of the current experiment was to identify the role of presynaptic GABAB receptors in these two processes. Previous work from our lab showed that genetic deletion or pharmacological inhibition of GABAB(1a) receptors that provide presynaptic inhibition on glutamatergic terminals reduces context specificity and leads to generalization. We therefore hypothesized that inactivation of these presynaptic GABAB receptors could be used to reduce the context specificity associated with fear extinction training and suppress renewal when mice are tested outside of the extinction context. Using CGP 36216, an antagonist specific for presynaptic GABAB receptors, we blocked presynaptic GABAB receptors using intracerebroventricular injections during various time points of extinction learning in male and female mice. Results showed that blocking these receptors pre- and post-extinction training le...
Source: Psychopharmacology - Category: Psychiatry Source Type: research