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Abstract
Anxiety disorders are associated with a failure to sufficiently extinguish fear memories. The serotonergic system (5-hydroxytryptamine, 5-HT) with the 5-HT transporter (5-HTT, SERT) is strongly implicated in the regulation of anxiety and fear. In the present study, we examined the effects of SERT deficiency on fear extinction in a differential fear conditioning paradigm in male and female rats. Fear-related behavior displayed during acquisition, extinction, and recovery, was measured through quantification of immobility and alarm 22-kHz ultrasonic vocalizations (USV). Trait-like inter-individual differences in novelty-seeking, anxiety-related behavior, habituation learning, cognitive performance, and pain sensitivity were examined for their predictive value in forecasting fear extinction. Our results show that SERT deficiency strongly affected the emission of 22-kHz USV during differential fear conditioning. During acquisition, extinction, and recovery, SERT deficiency consistently led to a reduction in 22-kHz USV emission. While SERT deficiency did not affect immobility during acquisition, genotype differences started to emerge during extinction, and during recovery rats lacking SERT showed higher levels of immobility than wildtype littermate controls. Recovery was reflected in increased levels of immobility but not 22-kHz USV emission. Prominent sex differences were evident. Among several measures for trait-like inter-individual differences, anxiety-related behavior had the best predictive quality.
Highlights
Excessive anxiety and fear are hallmarks of a number of neuropsychiatric disorders, most notably anxiety disorders, including phobias and post-traumatic stress disorder (PTSD) [1]
While no prominent genotype differences were evident in females, SERT deficiency affected body weight in males, with male SERT−/− rats showing consistently lower body weights than SERT+/− and SERT+/+ littermates
Extinction, and recovery, SERT deficiency consistently led to a reduction in 22-kHz ultrasonic vocalizations (USV) emission
Summary
Excessive anxiety and fear are hallmarks of a number of neuropsychiatric disorders, most notably anxiety disorders, including phobias and post-traumatic stress disorder (PTSD) [1]. Fear extinction is the inhibition of conditioned fear responses that is normally seen as a consequence of repeated exposure to a conditioned stimulus (CS) in the absence of an aversive unconditioned stimulus (UCS) [3]. It is a key component of the widely applied exposure therapy in the treatment of excessive anxiety and fear [4]. Recent efforts helped to dissect neurobiological mechanisms underlying fear extinction [7], little is still known about neurobiological factors associated with personality traits modulating fear extinction
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