Doxycycline has antidepressant effects by lowering nitric oxide in mice
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https://www.sciencedirect.com/science/article/abs/pii/S0166432823004825
"Doxycycline is an antibiotic that has shown neuroprotective, anti-inflammatory, and antidepressant-like effects. Low doses of doxycycline revert the behavioral and neuroinflammatory responses induced by lipopolysaccharide treatment in a mice model of depression. However, the molecular mechanisms involved in the antidepressant action of doxycycline are not yet understood. Doxycycline inhibits the synthesis of nitric oxide (NO), which increases after stress exposure. Inducible NO synthase (iNOS) inhibition also causes antidepressant-like effects in animal models sensitive to antidepressant-like effects such as the forced swimming test (FST). However, no direct study has yet investigated if the antidepressant-like effects of doxycycline could involve changes in NO-mediated neurotransmission. Therefore, this study aimed at investigating: i) the behavioral effects induced by doxycycline alone or in association with ineffective doses of a NO donor (sodium nitroprusside, SNP) or an iNOS inhibitor (1400 W) in mice subjected to the FST; and ii) doxycycline effects in NO metabolite levels in the prefrontal cortex and hippocampus these animals. Male mice (8 weeks) received i.p. injection of saline or doxycycline (10, 30, and 50 mg/kg), alone or combined with SNP (0.1, 0.5, and 1 mg/kg) or 1400 W (1, 3, and 10 µg/kg), and 30 min later were submitted to the FST. Animals were sacrificed immediately after, and NO metabolites nitrate/nitrite (NOx) were measured in the prefrontal cortex and hippocampus. Doxycycline (50 mg/kg) reduced both the immobility time in the FST and NOx levels in the prefrontal cortex of mice compared to the saline group. The antidepressant-like effect of doxycycline in the FST was prevented by SNP (1 mg/kg) pretreatment. Additionally, sub-effective doses of doxycycline (30 mg/kg) associated with 1400 W (1 µg/kg) induced an antidepressant-like effect in the FST. Altogether, our data suggest that the reducing NO levels in the prefrontal cortex through inhibition of iNOS could be related to acute doxycycline treatment resulting in rapid antidepressant-like effects in mice."
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@Mulloch94 thanks for posting this. I’m curious as to whether or not the benefit came from blocking or eliminating the endotoxin the mice were injected with, or if doxy itself lowered the iNOS that was upregulated due to the endotoxin?
Haidut had an old post talking about endotoxin being a typical cause of back pain. I’ve had unexplained back pain for a few years now that hits every morning but goes away as the day progresses. I assume it’s endotoxin related as I’ve had endotoxin issues in the past. I have used doxy, but never at the dose suggested here, (HED would be about 4mg/kg I believe). May give this a shot.
Thanks!
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@evan-hinkle said in Doxycycline has antidepressant effects by lowering nitric oxide in mice:
@Mulloch94 thanks for posting this. I’m curious as to whether or not the benefit came from blocking or eliminating the endotoxin the mice were injected with, or if doxy itself lowered the iNOS that was upregulated due to the endotoxin?
Haidut had an old post talking about endotoxin being a typical cause of back pain. I’ve had unexplained back pain for a few years now that hits every morning but goes away as the day progresses. I assume it’s endotoxin related as I’ve had endotoxin issues in the past. I have used doxy, but never at the dose suggested here, (HED would be about 4mg/kg I believe). May give this a shot.
Thanks!
No problem! I'm sure there's some synergy between lowering the endotoxin and blocking nitric oxide. But if I had to guess, at least according to this study, the main mechanism is behind the nitric oxide suppressing effects. Because when they administered sodium nitroprusside the antidepressant action of doxy was inhibited.