Fear Potentiated Startle

The startle response is an autonomic, reflexive response that is seen across species.45 It consists of a rapid and sequential muscle contraction that is thought to protect the body and facilitate the flight reaction to avoid a sudden attack. The fear potentiated startle (FPS) test can be used to assess differences in startle reactivity and in both animals and humans is thought to represent a form of anticipatory anxiety. The amplitude of the startle reflex can be augmented in the presence of a cue that has previously been paired with foot shock to provide a conditioned stimulus. A light or visual stimulus can be used as the conditioned stimulus and either sound or air puff to induce startle. The basic training paradigm for the FPS test consists of two phases, conditioning and testing. The conditioning phase includes two sets of rats: one set receives light-shock pairings at a fixed interval; and the second set receives lights and shock in random pairings. During the testing phase, startle is elicited by an auditory stimulus (e.g., 100 dB burst of white noise) in the presence or absence of the conditioned stimulus. The difference in the amplitude of the startle response in the presence or absence of the conditioned stimulus indicates the fear potentiated component of the response. A similar paradigm has been used on human subjects using an air puff as the startle stimulus and a wristband fitted with an electrode as the conditioned stimulus. A variety of drugs are effective in the rat FPS model, including the a2 agonist, clonidine, the opioid agonist morphine, GABAA positive allosteric modulators such as diazepam, and the 5HT1A partial agonist, buspirone.46 It is interesting to note that the data in the human FPS model are equivocal with respect to the effects of benzodiazepines, although this class of compounds has been shown to reduce the startle response in humans.47 This difference is perhaps consistent with the finding that this class of compounds does not work well in the treatment of fear-related disorders such as phobias.

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