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. 2022 Nov 23;23(23):14575.
doi: 10.3390/ijms232314575.

Mechanisms of Susceptibility and Resilience to PTSD: Role of Dopamine Metabolism and BDNF Expression in the Hippocampus

Vadim E Tseilikman  1 , Olga B Tseilikman  1   2 , Anton A Pashkov  1   3 , Irina S Ivleva  4 , Marina N Karpenko  4 , Vladislav A Shatilov  1 , Maxim S Zhukov  1 , Julia O Fedotova  5 , Marina V Kondashevskaya  6 , H Fred Downey  1   7 , Eugenia B Manukhina  1   7   8
Affiliations

Mechanisms of Susceptibility and Resilience to PTSD: Role of Dopamine Metabolism and BDNF Expression in the Hippocampus

Vadim E Tseilikman et al. Int J Mol Sci. .

Abstract

Susceptibility and resilience to post-traumatic stress disorder (PTSD) are recognized, but their mechanisms are not understood. Here, the hexobarbital sleep test (HST) was used to elucidate mechanisms of PTSD resilience or susceptibility. A HST was performed in rats 30 days prior to further experimentation. Based on the HST, the rats were divided into groups: (1) fast metabolizers (FM; sleep duration < 15 min); (2) slow metabolizers (SM; sleep duration ≥ 15 min). Then the SM and FM groups were subdivided into stressed (10 days predator scent, 15 days rest) and unstressed subgroups. Among stressed animals, only SMs developed experimental PTSD, and had higher plasma corticosterone (CORT) than stressed FMs. Thus, resilience or susceptibility to PTSD was consistent with changes in glucocorticoid metabolism. Stressed SMs had a pronounced decrease in hippocampal dopamine associated with increased expressions of catecholamine-O-methyl-transferase and DA transporter. In stressed SMs, a decrease in monoaminoxidase (MAO) A was associated with increased expressions of hippocampal MAO-A and MAO-B. BDNF gene expression was increased in stressed FMs and decreased in stressed SMs. These results demonstrate relationships between the microsomal oxidation phenotype, CORT concentration, and anxiety, and they help further the understanding of the role of the liver−brain axis during PTSD.

Keywords: BDNF; COMT; MAO; corticosterone; dopamine; hexobarbital sleep test; post-traumatic stress disorder.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Hippocampal DA (A), HVA (B) and DOPAC (C), and plasma CORT (D) in SM and FM rats. SM, slow metabolizer; FM, fast metabolizer; DOPAC, dihydroxyphenylacetic acid; HVA, homovanillic acid. * p < 0.05, ** p <0.01, *** p < 0.001 respective stressed vs. unstressed rats; # p < 0.05, ## p < 0.01 respective FM vs. SM.
Figure 2
Figure 2
Values are means ± SD. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. respective unstressed rats. ## p < 0.01, ### p < 0.001 vs. respective fast metabolizers. (A) BDNF concentration in hippocampus; (B) BDNF concentration in plasma. SM, slow metabolizer; FM, fast metabolizer; DAT, dopamine transporter; MAO, monoaminoxidase; COMT, catechol-O-methyltransferase; BDNF, brain-derived neurotrophic factor.
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