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M-07: Evaluation of the Anti-Anxiety Effect of Minocycline on Resident Intruder Model of PTSD in Golden Syrian Hamsters

Poster Presenter

Panini Patankar

Junior Resident
Seth G S Medical College & KEM Hospital
India

Objectives

To evaluate the anti-anxiety effect of minocycline hydrochloride on serum cortisol levels and behavioral tests in submissive hamsters post resident intrusion

Method

Nov 2018-Jan 2019 in CNS lab of Seth GSMC & KEMH, Mumbai. Golden Syrian Hamsters, larger(dominant) weighing >180 g & smaller(submissive) 90-120 g. Resident intrusion for 5 min. Drug given stat & serum cortisol level & behavioral test done after 24 hours. Results analysed & comparison between groups.

Results

The quantitative data collected consisted of serum cortisol levels among biochemical parameter. First the model was standardised. Later three groups of 8 submissive hamsters each were created. After resident intrusion, the submissive hamsters in one of the groups were given minocycline hydrochloride (test drug) i.p. in adequate calculated doses, the other group was given lorazepam (positive control) i.p & last group was given normal saline (vehicle control). Serum cortisol levels of three groups was done, post blood collection, using ELISA technique. There was extreme statistical significant difference between the cortisol levels in vehicle control group & minocycline group (p<0.001). Similarly, there was statistically significant difference between cortisol levels in vehicle control & positive control group (p=0.0148) However, the difference between positive control group & minocycline group was not statistically significant (p=0.2416). Open field test was done to assess the anti-anxiety effect of the drugs. Variables like time spent in inner & outer quadrant, time spent in central quadrant & total distance traveled were measured using image tracking software MAZEMASTER. The findings were like cortisol levels with statistically significant differences in each of the above parameters between minocycline & vehicle control group & between positive control & vehicle control group but no statistically significant difference between positive control & minocycline group. The other behavioural test done was Elevated Plus Maze (EPM) and the time spent in open arms was observed with same software. The time spent in open arm was statistically significantly more in minocycline group compared to both vehicle control group as well positive control group indicative of anti-anxiety effect. Thus, minocycline hydrochloride has at least similar anti-anxiety effect in this model compared to short acting benzodiazepines, holding true to our hypothesis.

Conclusion

The current line of treatment for Post Traumatic Stress Disorder (PTSD) is short acting benzodiazepines like Lorazepam followed by chronic use of Selective Serotonin Reuptake Inhibitors (SSRIs) like Fluoxetine. However, the currently used therapy has variable efficacy & myriad of adverse effects. For example, SSRIs are themselves initially anxiogenic & also increase REM sleep duration which further increases intensity of nightmares. Benzodiazepines additionally have abuse potential. Thus, there has been a constant need for development of new drug. In our study, we have chosen minocycline hydrochloride which is commonly used aminoglycoside antibiotic which has earlier shown to have certain neuroprotective effects. Our study clearly demonstrates that Minocycline hydrochloride is at least as effective as Lorazepam in our model of anxiety which has higher face validity as well as higher construct validity. If clinical studies are carried in the future and if the drug passes all the right check boxes, this drug can be revolutionary both in developed countries as well as developing countries. The incidence of acute anxiety & PTSD is believed to be as high as 45% in the world & it is extremely common in war veterans. With this drug, we can greatly help this target population of soldiers without much of adverse effects. PTSD is also extremely common post natural disasters especially in young adults resulting in psychological impact debilitating them through out life. Minocycline is believed to prevent memory reconsolidation post the stressful event & it will thus greatly help the survivors post natural disasters & other calamities. It was also greatly benefit the nations economically by saving cost on constant morbidity due to PTSD.