Accessible Requires Authentication Published by De Gruyter July 27, 2020

Beneficial role of central anticholinergic agent in preventing the development of symptoms in mouse model of post-traumatic stress disorder

Harpreet Kaur, Ravjot Kaur, Amteshwar Singh Jaggi and Anjana Bali

Abstract

Objectives

The present study was designed to investigate the effectiveness of trihexyphenidyl, a central anticholinergic drug, in preventing the post-traumatic stress disorder (PTSD) symptoms in a mouse model.

Methods

Mice were subjected to underwater trauma stress for 30 s on day 1 followed by three situational reminders (3rd, 7th and 14th day). Thereafter, the behavioral alterations including freezing behavior were noted on 21st day. The serum corticosterone levels were measured as a biochemical marker of trauma. Elevated plus maze test was done on day 1 and day 2 to assess the memory formation following exposure to trauma.

Results

Trauma and situational reminders were associated with a significant development of behavioral changes and freezing behavior on the 21st day. Moreover, there was also a significant decrease in the serum corticosterone levels. A single administration of trihexyphenidyl (2 and 5 mg/kg) significantly restored trauma associated-behavioral changes and serum corticosterone levels. Moreover, it significantly increased the transfer latency time on day 2 following stress exposure in comparison to normal mice suggesting the inhibition of memory formation during trauma exposure. Trihexyphenidyl also led to significant reduction in freezing behavior in response to situational reminders again suggesting the inhibition of formation of aversive fear memory.

Conclusion

The blockade of central muscarinic receptors may block the formation of aversive memory during the traumatic event, which may be manifested in form of decreased contextual fear response during situational reminders. Central anticholinergic agents may be potentially useful as prophylactic agents in preventing the development of PTSD symptoms.


Corresponding author: Dr. Anjana Bali, Department of Pharmacology, Akal College of Pharmacy and Technical education, Mastuana Sahib, Sangrur, 148001, India; and Department of Pharmacology, Central University of Punjab, Bathinda, India, Mobile: 9888780355, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Ethical approval: The experimental protocol was approved by the Institutional Animal Ethics Committee (IAEC) (Reg. no. 1407/PO/Re/S/11CPCSEA) and care of the animal’s experiment was carried out as per the guidelines of the Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA), Ministry of Environment and Forests, Government of India (approval no. ATRC/ 02/18).

  5. Informed consent: Informed consent was obtained from all individuals included in this study.

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Received: 2019-07-16
Accepted: 2020-04-18
Published Online: 2020-07-27

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