Crocin facilitates the effect of fear extinction on freezing behavior and BDNF level in a rat model of fear-conditioning

Posttraumatic stress disorder (PTSD) is a common neuropsychiatric disorder that develops after a particular physical or psychological trauma. In preclinical studies, fear conditioning method is used for the induction of PTSD-like model in rodents. Extinction learning, as a process in which a new memory trace is created and replaced with previous traumatic memory, may improve PTSD-like symptoms. On the other hand, crocin (active component of Crocus sativus or Saffron) may have a role in the treatment of different cognitive and mental disorders. In this study, we evaluated the effect of crocin, extinction learning, and combination of both on PTSD-like (freezing) behavior, pain threshold, and brain-derived neurotrophic factor (BDNF) transcription level in a rat model of fear conditioning. Crocin administration (50 mg/kg, i.p.) was done immediately after fear conditioning (0.6 mA, 3 sec, repeated for three times with 30 sec interval, paired with a sound: 75 dB for 3 sec). Extinction learning was done 1 h, or 1 h and 24 h, or 1 h and 24 h and 48 h, after fear conditioning. The results showed that extinction learning attenuated PTSD-like behavior, and 2- and 3-day extinction learning increased BDNF transcription level. Crocin (2- and 3-day) increased pain threshold, with no effect on PTSD-like behavior and BDNF level. In conclusion, we suggested that crocin (alone) may have not therapeutic effects on PTSD-like symptoms. However, the combination of crocin and extinction learning may lead to a greater effect on PTSD-like symptoms than extinction learning (alone); although further studies are needed.