Individual Differences in the Effects of a Muscarinic Antagonist on Cued Fear Recall and Extinction

Post-Traumatic Stress Disorder (PTSD) is characterized by an inability to extinguish fear after experiencing a traumatic event. The cholinergic system shows increased activity during fear learning and extinction, suggesting a role for cholinergic transmission in PTSD. Our lab has previously found that rats can be divided into extinction resistant (ER) and extinction competent (EC) phenotypes, with ER representing a PTSD-like phenotype. While women are more likely to develop PTSD, there is limited literature on the cholinergic system and recall of cued fear or extinction in female rats which are used as a model system due to their similar brain anatomy. This study tested the hypothesis that like males, ER and EC rats differ in cholinergic tone during extinction learning. In order to understand these sex differences, female rats were first conditioned with three tone-shock pairings. Rats were given the muscarinic receptor antagonist scopolamine (1.0 mg/kg, i.p.) or vehicle (saline) 30 minutes prior to assessing cued fear recall and extinction learning with twenty tone (cue) presentations. Later during statistical analysis, rats were divided into EC and ER groups based on freezing during the last ten tones of extinction learning. Rats treated with scopolamine were found to have decreased freezing compared to the control (vehicle treated) group during cued fear recall and extinction learning, suggesting scopolamine reduced cued fear recall. Extinction Competent rats also showed lower freezing compared to the ER group. EC rats treated with scopolamine showed significantly lower freezing than ER scopolamine rats, or either vehicle group, during the first five tone presentations. After extinction recall testing, rats were euthanized and plasma acetylcholinesterase activity was assayed. Acetylcholinesterase activity did not differ between extinction phenotypes or between drug treatment groups. These results suggest that female rats showed decreased recall of cued fear when treated with scopolamine. This effect was greater in the EC group compared to the ER group, suggesting that cholinergic tone may differ between ER and EC phenotypes.